Low Field Magnetic Stimulation (LFMS) in Subjects With Treatment-Resistant Depression (TRD)
Sponsor
Tal Medical, Inc. (Industry)
Overall Status
Completed
CT.gov ID
NCT02452892
Collaborator
(none)
122
12
4
13
10.2
0.8
Study Details
Study Description
Brief Summary
The purpose of this study is to compare the relative effectiveness of 20 and 60 minutes of Low-Field Magnetic Stimulation in relieving symptoms in patients with major depression who are treatment resistant.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
N/A |
Detailed Description
The primary objective of this study:
- To compare the relative efficacy, as measured by a change in the 6-item Hamilton Rating Scale for Depression (HAM-D6), of 20 and 60 minutes of LFMS compared to sham (placebo) in subjects with treatment resistant depression (TRD).
Secondary objectives:
-
To determine if subjects with TRD may respond to 120 minutes of LFMS.
-
To determine the persistence of response to LFMS therapy during the observation period.
-
To evaluate the safety and tolerability of LFMS.
Study Design
Study Type:
Interventional
Actual Enrollment
:
122 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:
Treatment
Official Title:
A Phase 2 Multicenter, Double-Blind, Placebo-Controlled, Dose Optimization Study of Low Field Magnetic Stimulation (LFMS) in Subjects With Treatment-Resistant Depression (TRD)
Study Start Date
:
Sep 1, 2015
Actual Primary Completion Date
:
Sep 1, 2016
Actual Study Completion Date
:
Oct 1, 2016
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Sham Comparator: LFMS Sham For sham therapy, the device will be on; however, no magnetic field stimulation will be delivered. Low field magnetic stimulation (no magnetic field for sham) will be administered using a portable tabletop device capable of generating time-varying electromagnetic fields of LFMS. |
Device: LFMS
Low field magnetic stimulation (1 kilohertz oscillating magnetic field) will be administered using a portable tabletop device capable of generating time-varying electromagnetic fields of LFMS. For sham therapy, the device will be on; however, no magnetic field stimulation will be delivered.
Other Names:
|
| Active Comparator: LFMS 20 minutes LFMS 20 minutes + Sham 40 min.Low field magnetic stimulation (1 kilohertz oscillating magnetic field) will be administered using a portable tabletop device capable of generating time-varying electromagnetic fields of LFMS. |
Device: LFMS
Low field magnetic stimulation (1 kilohertz oscillating magnetic field) will be administered using a portable tabletop device capable of generating time-varying electromagnetic fields of LFMS. For sham therapy, the device will be on; however, no magnetic field stimulation will be delivered.
Other Names:
|
| Active Comparator: LFMS 60 minutes LFMS 60 minutes.Low field magnetic stimulation (1 kilohertz oscillating magnetic field) will be administered using a portable tabletop device capable of generating time-varying electromagnetic fields of LFMS. |
Device: LFMS
Low field magnetic stimulation (1 kilohertz oscillating magnetic field) will be administered using a portable tabletop device capable of generating time-varying electromagnetic fields of LFMS. For sham therapy, the device will be on; however, no magnetic field stimulation will be delivered.
Other Names:
|
| Other: LFMS 120 min Week 2 subjects may be re-randomized to receive LFMS 120 minutes. Low field magnetic stimulation (1 kilohertz oscillating magnetic field) will be administered using a portable tabletop device capable of generating time-varying electromagnetic fields of LFMS. |
Device: LFMS
Low field magnetic stimulation (1 kilohertz oscillating magnetic field) will be administered using a portable tabletop device capable of generating time-varying electromagnetic fields of LFMS. For sham therapy, the device will be on; however, no magnetic field stimulation will be delivered.
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Change From Baseline to ( Day 4) in the 6-item Hamilton Rating Scale for Depression (HAM-D6) Total Score. [Week 1 Day 4]
Hamilton Rating Scales for Depression were designed to measure the severity of depressive symptoms in subjects with primary depressive illness. HAM-D6 is a subset of the HAM-D17 that assesses 6 items associated with major depression. The scale uses HAM-D17 items 1, 2, 7, 8, 10 and 13. Item 13 is scored 0 to 2 and all others are scored 0 to 4. Total score ranges from 0 to 22; higher score indicates more depression. Change from baseline: mean score at Week 1 Day 4 minus mean score at baseline". Week 1 Day 4 : Change from baseline to the end of the efficacy period ( Day 4) in the 6-item Hamilton Rating Scale for Depression (HAM-D6) total score .Responders at Day 4 will be defined as those subjects who achieve a decrease in HAM-D6 total score of 50% or more compared to baseline (Day 1, Week 1). All other subjects will be deemed to be non-responders at Day 4. Each patient's total score is his/her own reference for determining a decrease of 50% or more.
Secondary Outcome Measures
- Change From Day 4 in HAM-D6 Total Score at Day 11 for Week 1 Non-responders: Response to 120 Minutes LFMS [Day 11 (Week 2)]
Hamilton Rating Scales for Depression were designed to measure the severity of depressive symptoms in subjects with primary depressive illness. HAM-D6 is a subset of the HAM-D17 that assesses 6 items associated with major depression. The scale uses HAM-D17 items 1, 2, 7, 8, 10 and 13. Item 13 is scored 0 to 2 and all others are scored 0 to 4. Total score ranges from 0 to 22; higher score indicates more depression. Change from Day 11: mean score at Week 2 Day 11 minus mean score at Day 4". To determine if subjects with TRD who are non-responders to 0, 20 or 60 minutes of LFMS on Day 4 may respond to 120 minutes of LFMS at the end of Day 11. Responders will be defined as those subjects who achieve a decrease in HAM-D6 total score of 50% or more compared to baseline (Day 1, Week 1). All other subjects will be deemed to be non-responders. Each patient's total score is his/her own reference for determining a decrease of 50% or more.
- Day 4 Responders: Persistence of Effect Based on Pre-specified HAM-D6 Total Score [Day 42]
To determine the persistence of response to LFMS therapy during a four-week follow-up period in subjects who were responders at Day 4. Persistence of response was achieved if during Week 2 post baseline visits and follow-up visits subjects' 6-item Hamilton Rating Scale for Depression (HAM-D6) total scores were lower than or equal to 50% of the baseline ( Day1 Week1) scores. Non-responder imputation method was used where missing post-baseline dichotomous ("yes or no") were imputed as non-responder. Logistic regression model used to compare treatment groups for each visit, where the model considers the treatment, age and gender as covariates.
Eligibility Criteria
Criteria
Ages Eligible for Study:
18 Years
and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria: (Key)
-
Meets the Diagnostic and Statistical Manual of Mental Disorder, 5th Edition (DSM-5) criteria for Major Depressive Disorder (MDD), as determined by psychiatric evaluation.
-
Has TRD of the current MDE, as assessed at the site by the Massachusetts General Hospital/Antidepressant Treatment Response Questionnaire (MGH/ATRQ).
-
On an adequate dose of one antidepressant therapy (ADT) for at least eight weeks prior to the screening visit (Visit 1). The ADT dose must be stable for at least four weeks prior to the screening visit (Visit 1). Subjects must be willing to remain on the same stable dose of ADT upon signing the informed consent form until the end of the treatment observation period (end of Week 2) and, where possible, to the end of study participation
Exclusion Criteria: (Key)
-
Have failed four or more lifetime adequate ADT treatment regimens (including the ongoing ADT for the current MDE).
-
Have been treated with adjunctive antipsychotic medication with an antidepressant for at least two weeks during the current depressive episode.
-
Are deemed to be at significant risk for suicidal behavior
-
Are unable to lie on their back for the duration of study treatment
-
Have a lifetime history of:
-
Delirium, dementia, amnestic, or other cognitive disorder;
-
Schizophrenia or any psychotic disorder, based on the Structured Clinical Interview for DSM-5 Axis I Disorders Patient Edition (SCID-I/P);
-
Bipolar I or II disorder, based on the SCID-I/P.
- Have a current DSM-5 diagnosis at the screening visit (Visit 1) of:
-
An eating disorder active within the 12 months prior to the screening visit (Visit 1);
-
Comorbid anxiety disorders that predominate over MDD, as assessed by the investigator;
-
Alcohol or substance use disorder active within the 12 months prior to the screening visit (Visit 1);
-
Clinically significant DSM-5 Axis II disorder.
-
Have ever received electroconvulsive therapy, vagal nerve stimulation, deep brain stimulation or repetitive transcranial magnetic stimulation.
-
Have a non-removable programmable device or appliance such as cardiac pacemakers or cochlear implants.
-
Have any non-removable ferromagnetic implants, or conductive or other magnetic sensitive materials present in the head or neck .
-
Have a lifetime history of seizures or clinically significant electroencephalography abnormalities. A history of childhood febrile seizures is permitted.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | CNS Trials | Garden Grove | California | United States | 92845 |
| 2 | Synergy Escondido | Lemon Grove | California | United States | 91945 |
| 3 | Pacific Trials Partners | Oakland | California | United States | 94612 |
| 4 | Sarkis Clinical Trials | Gainesville | Florida | United States | 32607 |
| 5 | CNS Healthcare | Jacksonville | Florida | United States | 32256 |
| 6 | Segal Institute | Lauderhill | Florida | United States | 33319 |
| 7 | Institute for Advanced Medical Research | Alpharetta | Georgia | United States | 30005 |
| 8 | Radiant Research | Atlanta | Georgia | United States | 30328 |
| 9 | Neurobehavioral-Clinical Research | Canton | Ohio | United States | 44718 |
| 10 | Midwest Clinical | Dayton | Ohio | United States | 45417 |
| 11 | Future Search Trials | Dallas | Texas | United States | 75231 |
| 12 | Northwest Clinical Research Center | Bellevue | Washington | United States | 98007 |
Sponsors and Collaborators
- Tal Medical, Inc.
Investigators
- Study Chair: Atul Pande, MD, Tal Medical
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.Responsible Party:
Tal Medical, Inc.
ClinicalTrials.gov Identifier:
NCT02452892
Other Study ID Numbers:
- TAL-02-007
First Posted:
May 25, 2015
Last Update Posted:
Dec 5, 2017
Last Verified:
Sep 1, 2017
Individual Participant Data (IPD) Sharing Statement:
Undecided
Plan to Share IPD:
Undecided
Keywords provided by Tal Medical, Inc.
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | 12clinical study sites in the US recruited 122 subjects that were randomized into the study. The date of first subject enrollment was 03 September 2015 and the date of last subject enrolled was 22 July 2016. |
|---|---|
| Pre-assignment Detail | Subject screening period was up to 14 days before receiving first study treatment. Subjects were contacted by an independent Massachusetts General Hospital-Clinical Trials Network and Institute (MGH-CTNI) rater to perform the Antidepressant Treatment Response Questionnaire (ATRQ) and SAFER assessments to confirm eligibility. |
| Arm/Group Title | LFMS Sham | LFMS 20 Minutes | LFMS 60 Minutes | LFMS 120 Min |
|---|---|---|---|---|
| Arm/Group Description | For sham therapy, the device will be on; however, no magnetic field stimulation will be delivered.Week 1 subjects were randomly assigned using 1:1:1 allocation to LFMS Sham, LFMS 20 min., or LFMS 60 min. For Week 2 subjects were reassigned to LFMS Sham, LFMS 20min, LFMS 60min, or LFMS 120min. on the basis of their response to treatment received in Week 1 and their original treatment allocation. | LFMS 20 minutes + Sham 40 min.Low field magnetic stimulation (1 kilohertz oscillating magnetic field) will be administered using a portable tabletop device capable of generating time-varying electromagnetic fields of LFMS. Week 1 subjects were randomly assigned using 1:1:1 allocation to LFMS Sham, LFMS 20 min., or LFMS 60 min. For Week 2, subjects were reassigned to LFMS Sham, LFMS 20min, LFMS 60min, or LFMS 120min. on the basis of their response to treatment received in Week 1 and their original treatment allocation. | LFMS 60 minutes.Low field magnetic stimulation (1 kilohertz oscillating magnetic field) will be administered using a portable tabletop device capable of generating time-varying electromagnetic fields of LFMS. Week 1: Subjects were randomly assigned using 1:1:1 allocation to LFMS Sham, LFMS 20 min., or LFMS 60 min. For Week 2 subjects were reassigned to LFMS Sham, LFMS 20min, LFMS 60min, or LFMS 120min. on the basis of their response to treatment received in Week 1 and their original treatment allocation. | Week 2: Subjects may be re-randomized to receive LFMS 120 minutes. Low field magnetic stimulation (1 kilohertz oscillating magnetic field) will be administered using a portable tabletop device capable of generating time-varying electromagnetic fields of LFMS. Week 1 subjects were randomly assigned using 1:1:1 allocation to LFMS Sham, LFMS 20 min., or LFMS 60 min. For Week 2 subjects were reassigned to LFMS Sham, LFMS 20min, LFMS 60min, or LFMS 120min. on the basis of their response to treatment received in Week 1 and their original treatment allocation. |
| Period Title: Week 1 Initial Randommization | ||||
| STARTED | 41 | 40 | 41 | 0 |
| COMPLETED | 40 | 40 | 40 | 0 |
| NOT COMPLETED | 1 | 0 | 1 | 0 |
| Period Title: Week 1 Initial Randommization | ||||
| STARTED | 65 | 7 | 7 | 41 |
| Non-reponders | 38 | 0 | 0 | 41 |
| Responders | 27 | 7 | 7 | 0 |
| COMPLETED | 63 | 7 | 7 | 39 |
| NOT COMPLETED | 2 | 0 | 0 | 2 |
| Period Title: Week 1 Initial Randommization | ||||
| STARTED | 63 | 7 | 7 | 39 |
| COMPLETED | 62 | 7 | 7 | 38 |
| NOT COMPLETED | 1 | 0 | 0 | 1 |
Baseline Characteristics
| Arm/Group Title | LFMS Sham | LFMS 20 Minutes | LFMS 60 Minutes | LFMS 120 Min | Total |
|---|---|---|---|---|---|
| Arm/Group Description | For sham therapy, the device will be on; however, no magnetic field stimulation will be delivered. Low field magnetic stimulation (no magnetic field for sham) will be administered using a portable tabletop device capable of generating time-varying electromagnetic fields of LFMS. LFMS: Low field magnetic stimulation (1 kHz oscillating magnetic field) will be administered using a portable tabletop device capable of generating time-varying electromagnetic fields of LFMS. For sham therapy, the device will be on; however, no magnetic field stimulation will be delivered. | LFMS 20 minutes + Sham 40 min.Low field magnetic stimulation (1 kilohertz oscillating magnetic field) will be administered using a portable tabletop device capable of generating time-varying electromagnetic fields of LFMS. LFMS: Low field magnetic stimulation (1 kHz oscillating magnetic field) will be administered using a portable tabletop device capable of generating time-varying electromagnetic fields of LFMS. For sham therapy, the device will be on; however, no magnetic field stimulation will be delivered. | LFMS 60 minutes.Low field magnetic stimulation (1 kilohertz oscillating magnetic field) will be administered using a portable tabletop device capable of generating time-varying electromagnetic fields of LFMS. LFMS: Low field magnetic stimulation (1 kHz oscillating magnetic field) will be administered using a portable tabletop device capable of generating time-varying electromagnetic fields of LFMS. For sham therapy, the device will be on; however, no magnetic field stimulation will be delivered. | Week 2 subjects may be re-randomized to receive LFMS 120 minutes. Low field magnetic stimulation (1 kilohertz oscillating magnetic field) will be administered using a portable tabletop device capable of generating time-varying electromagnetic fields of LFMS. LFMS: Low field magnetic stimulation (1 kHz oscillating magnetic field) will be administered using a portable tabletop device capable of generating time-varying electromagnetic fields of LFMS. For sham therapy, the device will be on; however, no magnetic field stimulation will be delivered. | Total of all reporting groups |
| Overall Participants | 41 | 40 | 41 | 0 | 122 |
| Age (Count of Participants) | |||||
| <=18 years |
0
0%
|
0
0%
|
0
0%
|
0
NaN
|
0
0%
|
| Between 18 and 65 years |
37
90.2%
|
35
87.5%
|
37
90.2%
|
0
NaN
|
109
89.3%
|
| >=65 years |
4
9.8%
|
5
12.5%
|
4
9.8%
|
0
NaN
|
13
10.7%
|
| Sex: Female, Male (Count of Participants) | |||||
| Female |
23
56.1%
|
23
57.5%
|
26
63.4%
|
0
NaN
|
72
59%
|
| Male |
18
43.9%
|
17
42.5%
|
15
36.6%
|
0
NaN
|
50
41%
|
| Race/Ethnicity, Customized (Count of Participants) | |||||
| White |
31
75.6%
|
28
70%
|
27
65.9%
|
0
NaN
|
86
70.5%
|
| Black or African American |
9
22%
|
9
22.5%
|
11
26.8%
|
0
NaN
|
29
23.8%
|
| Asian |
1
2.4%
|
3
7.5%
|
2
4.9%
|
0
NaN
|
6
4.9%
|
| Other |
0
0%
|
0
0%
|
1
2.4%
|
0
NaN
|
1
0.8%
|
Outcome Measures
| Title | Change From Baseline to ( Day 4) in the 6-item Hamilton Rating Scale for Depression (HAM-D6) Total Score. |
|---|---|
| Description | Hamilton Rating Scales for Depression were designed to measure the severity of depressive symptoms in subjects with primary depressive illness. HAM-D6 is a subset of the HAM-D17 that assesses 6 items associated with major depression. The scale uses HAM-D17 items 1, 2, 7, 8, 10 and 13. Item 13 is scored 0 to 2 and all others are scored 0 to 4. Total score ranges from 0 to 22; higher score indicates more depression. Change from baseline: mean score at Week 1 Day 4 minus mean score at baseline". Week 1 Day 4 : Change from baseline to the end of the efficacy period ( Day 4) in the 6-item Hamilton Rating Scale for Depression (HAM-D6) total score .Responders at Day 4 will be defined as those subjects who achieve a decrease in HAM-D6 total score of 50% or more compared to baseline (Day 1, Week 1). All other subjects will be deemed to be non-responders at Day 4. Each patient's total score is his/her own reference for determining a decrease of 50% or more. |
| Time Frame | Week 1 Day 4 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Subjects in the All Randomized set who completed at least one treatment session and had at least one post baseline primary efficacy assessment. |
| Arm/Group Title | LFMS Sham | LFMS 20 Minutes | LFMS 60 Minutes |
|---|---|---|---|
| Arm/Group Description | For sham therapy, the device will be on; however, no magnetic field stimulation will be delivered. Low field magnetic stimulation (no magnetic field for sham) will be administered using a portable tabletop device capable of generating time-varying electromagnetic fields of LFMS. LFMS: Low field magnetic stimulation (1 kHz oscillating magnetic field) will be administered using a portable tabletop device capable of generating time-varying electromagnetic fields of LFMS. For sham therapy, the device will be on; however, no magnetic field stimulation will be delivered. | LFMS 20 minutes + Sham 40 min.Low field magnetic stimulation (1 kilohertz oscillating magnetic field) will be administered using a portable tabletop device capable of generating time-varying electromagnetic fields of LFMS. LFMS: Low field magnetic stimulation (1 kHz oscillating magnetic field) will be administered using a portable tabletop device capable of generating time-varying electromagnetic fields of LFMS. For sham therapy, the device will be on; however, no magnetic field stimulation will be delivered. | LFMS 60 minutes.Low field magnetic stimulation (1 kilohertz oscillating magnetic field) will be administered using a portable tabletop device capable of generating time-varying electromagnetic fields of LFMS. LFMS: Low field magnetic stimulation (1 kHz oscillating magnetic field) will be administered using a portable tabletop device capable of generating time-varying electromagnetic fields of LFMS. For sham therapy, the device will be on; however, no magnetic field stimulation will be delivered. |
| Measure Participants | 41 | 40 | 41 |
| Least Squares Mean (95% Confidence Interval) [units on a scale] |
-4.0
|
-4.2
|
-4.9
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | LFMS Sham, LFMS 60 Minutes |
|---|---|---|
| Comments | Comparisons of 60 min LFMS vs. sham, LSMean diff with 95% Confidence Interval (CI) reported. Hypothesis 1: no difference between 60 min. LFMS and sham therapy in mean change from baseline (Day 1) to end of Tx Day 4 in HAM-D6 total score. If hypothesis is rejected at significance level of 0.05, then second hypothesis will be tested. Hypothesis 2:no difference between 20 min. LFMS & sham therapy in mean change from baseline (Day 1) to the end of Tx. Day 4 in HAM-D6 total score. | |
| Type of Statistical Test | Superiority | |
| Comments | To control for multiple comparisons in the primary endpoint analysis, a hierarchical approach was taken. First LFMS 60min. was compared to LFMS sham. If p<0.05 for this comparison, then LFMS 20min. was formally compared to LFMS sham for statistical significance. | |
| Statistical Test of Hypothesis | p-Value | 0.307 |
| Comments | P-value displayed for 60min. Mixed Model Repeated Measures (MMRM) model. | |
| Method | Mixed Models Analysis | |
| Comments | Week 1 baseline HAM-D6 total score, treatment,visit treatment*visit age, & gender included in model. Visit was the repeated measure within subjects. | |
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | LFMS Sham, LFMS 20 Minutes |
|---|---|---|
| Comments | Comparisons of 20 min LFMS vs. sham, LSMean diff with 95% Confidence Interval (CI) reported. Hypothesis 1: no difference between 60 min. LFMS and sham therapy in mean change from baseline (Day 1) to end of Tx Day 4 in HAM-D6 total score. If hypothesis is rejected at significance level of 0.05, then second hypothesis will be tested. Hypothesis 2:no difference between 20 min. LFMS & sham therapy in mean change from baseline (Day 1) to the end of Tx. Day 4 in HAM-D6 total score. | |
| Type of Statistical Test | Superiority | |
| Comments | To control for multiple comparisons in the primary endpoint analysis, a hierarchical approach was taken. First LFMS 60min. was compared to LFMS sham. If p<0.05 for this comparison, then LFMS 20min. was formally compared to LFMS sham for statistical significance. | |
| Statistical Test of Hypothesis | p-Value | 0.859 |
| Comments | P-value displayed for 20min. Mixed Model Repeated Measures (MMRM) model. | |
| Method | Mixed Models Analysis | |
| Comments | Week 1 baseline HAM-D6 total score, treatment,visit treatment*visit age, & gender included in model. Visit was the repeated measure within subjects. | |
| Title | Change From Day 4 in HAM-D6 Total Score at Day 11 for Week 1 Non-responders: Response to 120 Minutes LFMS |
|---|---|
| Description | Hamilton Rating Scales for Depression were designed to measure the severity of depressive symptoms in subjects with primary depressive illness. HAM-D6 is a subset of the HAM-D17 that assesses 6 items associated with major depression. The scale uses HAM-D17 items 1, 2, 7, 8, 10 and 13. Item 13 is scored 0 to 2 and all others are scored 0 to 4. Total score ranges from 0 to 22; higher score indicates more depression. Change from Day 11: mean score at Week 2 Day 11 minus mean score at Day 4". To determine if subjects with TRD who are non-responders to 0, 20 or 60 minutes of LFMS on Day 4 may respond to 120 minutes of LFMS at the end of Day 11. Responders will be defined as those subjects who achieve a decrease in HAM-D6 total score of 50% or more compared to baseline (Day 1, Week 1). All other subjects will be deemed to be non-responders. Each patient's total score is his/her own reference for determining a decrease of 50% or more. |
| Time Frame | Day 11 (Week 2) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Only non-responders at end of Day 4 comprise this Wk 2 analysis . (Non-responders were defined as those who didn't reach a decrease in 6-item Hamilton Rating Scale for Depression (HAM-D6) total score of 50% compared to baseline Day 1, Week 1). 41 subjects entered Week 2: 1 subject withdrew consent on Day 8 and was not part of the Full Analysis Set. |
| Arm/Group Title | LFMS Sham | LFMS 120 Min |
|---|---|---|
| Arm/Group Description | For sham therapy, the device will be on; however, no magnetic field stimulation will be delivered. Low field magnetic stimulation (no magnetic field for sham) will be administered using a portable tabletop device capable of generating time-varying electromagnetic fields of LFMS. LFMS: Low field magnetic stimulation (1 kHz oscillating magnetic field) will be administered using a portable tabletop device capable of generating time-varying electromagnetic fields of LFMS. For sham therapy, the device will be on; however, no magnetic field stimulation will be delivered. | Week 2 subjects may be re-randomized to receive LFMS 120 minutes. Low field magnetic stimulation (1 kilohertz oscillating magnetic field) will be administered using a portable tabletop device capable of generating time-varying electromagnetic fields of LFMS. LFMS: Low field magnetic stimulation (1 kHz oscillating magnetic field) will be administered using a portable tabletop device capable of generating time-varying electromagnetic fields of LFMS. For sham therapy, the device will be on; however, no magnetic field stimulation will be delivered. |
| Measure Participants | 38 | 40 |
| Least Squares Mean (95% Confidence Interval) [units on a scale] |
-2.6
|
-2.6
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | LFMS Sham, LFMS 20 Minutes |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.966 |
| Comments | P-value is not adjusted for multiple comparisons. P-value was estimated from Mixed Model Repeated Measures (MMRM) model. | |
| Method | Mixed Models Analysis | |
| Comments | Week 2 baseline HAM-D6 total score, treatment, visit, treatment*visit, age, & gender included in model. Visit was the repeated measure within subject. | |
| Title | Day 4 Responders: Persistence of Effect Based on Pre-specified HAM-D6 Total Score |
|---|---|
| Description | To determine the persistence of response to LFMS therapy during a four-week follow-up period in subjects who were responders at Day 4. Persistence of response was achieved if during Week 2 post baseline visits and follow-up visits subjects' 6-item Hamilton Rating Scale for Depression (HAM-D6) total scores were lower than or equal to 50% of the baseline ( Day1 Week1) scores. Non-responder imputation method was used where missing post-baseline dichotomous ("yes or no") were imputed as non-responder. Logistic regression model used to compare treatment groups for each visit, where the model considers the treatment, age and gender as covariates. |
| Time Frame | Day 42 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Subjects who were HAM-D6 Day 4 responders, defined as those subjects who achieved a 50% or greater decrease in their HAM-D6 total score compared to Baseline ( Day1, Wk 1). |
| Arm/Group Title | LFMS 20 Minutes | LFMS 60 Minutes | LFMS Sham |
|---|---|---|---|
| Arm/Group Description | LFMS 20 minutes + Sham 40 min.Low field magnetic stimulation (1 kilohertz oscillating magnetic field) will be administered using a portable tabletop device capable of generating time-varying electromagnetic fields of LFMS. LFMS: Low field magnetic stimulation (1 kHz oscillating magnetic field) will be administered using a portable tabletop device capable of generating time-varying electromagnetic fields of LFMS. For sham therapy, the device will be on; however, no magnetic field stimulation will be delivered. | LFMS 60 minutes.Low field magnetic stimulation (1 kilohertz oscillating magnetic field) will be administered using a portable tabletop device capable of generating time-varying electromagnetic fields of LFMS. LFMS: Low field magnetic stimulation (1 kHz oscillating magnetic field) will be administered using a portable tabletop device capable of generating time-varying electromagnetic fields of LFMS. For sham therapy, the device will be on; however, no magnetic field stimulation will be delivered. | For sham therapy, the device will be on; however, no magnetic field stimulation will be delivered. Low field magnetic stimulation (no magnetic field for sham) will be administered using a portable tabletop device capable of generating time-varying electromagnetic fields of LFMS. LFMS: Low field magnetic stimulation (1 kHz oscillating magnetic field) will be administered using a portable tabletop device capable of generating time-varying electromagnetic fields of LFMS. For sham therapy, the device will be on; however, no magnetic field stimulation will be delivered. |
| Measure Participants | 13 | 14 | 14 |
| Number [percentage of LFMS responders] |
53.8
|
57.1
|
78.6
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | LFMS 20 Minutes, LFMS 60 Minutes |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | The persistence rate calculated based on Week 1 treatment group: 20 minutes LFMS, 60 minutes LFMS and sham therapy. | |
| Statistical Test of Hypothesis | p-Value | 0.294 |
| Comments | For 60 min LFMS, P-value not adjusted for multiple comparisons. P-value estimated using LR model including Wk2 baseline HAM-D6 total score, treatment, age & gender as covariates. | |
| Method | Regression, Logistic | |
| Comments | Non-responder imputation (NRI) for missing data, where missing post-baseline results were considered non-response | |
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | LFMS Sham, LFMS 60 Minutes |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | The persistence rate calculated based on Week 1 treatment group: 20 minutes LFMS, 60 minutes LFMS and sham therapy. | |
| Statistical Test of Hypothesis | p-Value | 0.232 |
| Comments | For 20min. LFMS, P-value not adjusted for multiple comparisons. P-value estimated using Logistic Regression model including Wk2 baseline HAM-D6 total score, treatment, age & gender as covariates. | |
| Method | Regression, Logistic | |
| Comments | Non-responder imputation (NRI) for missing data, where missing post-baseline results were considered non-response | |
| Title | Montgomery-Asberg Depression Rating Scale (MADRS): Change From Week 1 Baseline (Day 1) to End of Week 1 (Day 4) |
|---|---|
| Description | The MADRS is a 10-item checklist designed to measure the overall severity of depressive symptoms in subjects with Major Depressive Disorder (MDD). Individual items are rated on a scale of 0 to 6 in which a score of 6 represents the most severe symptoms for each item assessed. The total score ranges from 0 to 60. Remission of depression based on the MADRS is defined as a subject with a MADRS total score of ≤11 at endpoint. A responder on the MADRS is defined as a 50% or greater reduction from baseline in total MADRS score |
| Time Frame | Day 4 Week 1 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full Analysis Set, Week1 |
| Arm/Group Title | LFMS Sham | LFMS 20 Minutes | LFMS 60 Minutes |
|---|---|---|---|
| Arm/Group Description | For sham therapy, the device will be on; however, no magnetic field stimulation will be delivered. Low field magnetic stimulation (no magnetic field for sham) will be administered using a portable tabletop device capable of generating time-varying electromagnetic fields of LFMS. LFMS: Low field magnetic stimulation (1 kHz oscillating magnetic field) will be administered using a portable tabletop device capable of generating time-varying electromagnetic fields of LFMS. For sham therapy, the device will be on; however, no magnetic field stimulation will be delivered. | LFMS 20 minutes + Sham 40 min.Low field magnetic stimulation (1 kilohertz oscillating magnetic field) will be administered using a portable tabletop device capable of generating time-varying electromagnetic fields of LFMS. LFMS: Low field magnetic stimulation (1 kHz oscillating magnetic field) will be administered using a portable tabletop device capable of generating time-varying electromagnetic fields of LFMS. For sham therapy, the device will be on; however, no magnetic field stimulation will be delivered. | LFMS 60 minutes.Low field magnetic stimulation (1 kilohertz oscillating magnetic field) will be administered using a portable tabletop device capable of generating time-varying electromagnetic fields of LFMS. LFMS: Low field magnetic stimulation (1 kHz oscillating magnetic field) will be administered using a portable tabletop device capable of generating time-varying electromagnetic fields of LFMS. For sham therapy, the device will be on; however, no magnetic field stimulation will be delivered. |
| Measure Participants | 41 | 40 | 41 |
| Least Squares Mean (95% Confidence Interval) [units on a scale] |
-7.58
|
-8.09
|
-10.32
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | LFMS Sham, LFMS 60 Minutes |
|---|---|---|
| Comments | Estimates for LS Means, confidence intervals, difference in LS means and p-value are from an ANCOVA model with treatment, age, sex as factors and baseline negative MADRS score as a covariate. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0932 |
| Comments | P-value is not adjusted for multiple comparisons. | |
| Method | ANCOVA | |
| Comments | P-value was estimated using ANCOVA model with treatment, age, & gender as factors and baseline negative MADRS score as a covariate. | |
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | LFMS Sham, LFMS 20 Minutes |
|---|---|---|
| Comments | Estimates for LS Means, confidence intervals, difference in LS means and p-value are from an ANCOVA model with treatment, age, sex as factors and baseline negative MADRS score as a covariate. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.7509 |
| Comments | The p-value is not adjusted for multiple comparisons. | |
| Method | ANCOVA | |
| Comments | P-value was estimated using ANCOVA model with treatment, age, & gender as factors and baseline negative MADRS score as a covariate. | |
| Title | Positive and Negative Affect Schedule (PANAS): Change From Baseline at Day 4 in Positive Score |
|---|---|
| Description | The PANAS comprises two mood scales, one that measures positive affect and the other that measures negative affect. Used as a psychometric scale, the PANAS can show relationships between positive and negative affect with personality stats and traits. Descriptors are used to define their meanings. Subjects completing the PANAS are required to respond to a 20-item test using 5-point scale that ranges from very slightly or not at all (1) to extremely (5).To calculate the positive affect score, added scores on items 1, 3, 5, 9, 10, 12, 14, 16, 17, and 19. Scores can range from 10-50, which higher scores representing higher levels of positive affect, or the extent to which the individual feels enthusiastic, active and alert. |
| Time Frame | Day 4 Week 1 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full Analysis Set (Week 1). |
| Arm/Group Title | LFMS Sham | LFMS 20 Minutes | LFMS 60 Minutes |
|---|---|---|---|
| Arm/Group Description | For sham therapy, the device will be on; however, no magnetic field stimulation will be delivered. Low field magnetic stimulation (no magnetic field for sham) will be administered using a portable tabletop device capable of generating time-varying electromagnetic fields of LFMS. LFMS: Low field magnetic stimulation (1 kHz oscillating magnetic field) will be administered using a portable tabletop device capable of generating time-varying electromagnetic fields of LFMS. For sham therapy, the device will be on; however, no magnetic field stimulation will be delivered. | LFMS 20 minutes + Sham 40 min.Low field magnetic stimulation (1 kilohertz oscillating magnetic field) will be administered using a portable tabletop device capable of generating time-varying electromagnetic fields of LFMS. LFMS: Low field magnetic stimulation (1 kHz oscillating magnetic field) will be administered using a portable tabletop device capable of generating time-varying electromagnetic fields of LFMS. For sham therapy, the device will be on; however, no magnetic field stimulation will be delivered. | LFMS 60 minutes.Low field magnetic stimulation (1 kilohertz oscillating magnetic field) will be administered using a portable tabletop device capable of generating time-varying electromagnetic fields of LFMS. LFMS: Low field magnetic stimulation (1 kHz oscillating magnetic field) will be administered using a portable tabletop device capable of generating time-varying electromagnetic fields of LFMS. For sham therapy, the device will be on; however, no magnetic field stimulation will be delivered. |
| Measure Participants | 41 | 40 | 41 |
| Least Squares Mean (95% Confidence Interval) [units on a scale] |
1.67
|
3.62
|
3.24
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | LFMS Sham, LFMS 60 Minutes |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | Positive score is the sum of 10 items: 1,3,5,9,10,12,14,16,17,19. | |
| Statistical Test of Hypothesis | p-Value | 0.2672 |
| Comments | P-value not adjusted for multiple comparisons. | |
| Method | ANCOVA | |
| Comments | P-value estimated using ANCOVA model with treatment,age,& gender as factors & baseline positive PANAS score as a covariate. | |
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | LFMS Sham, LFMS 20 Minutes |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | Positive score is the sum of 10 items: 1,3,5,9,10,12,14,16,17,19. | |
| Statistical Test of Hypothesis | p-Value | 0.1660 |
| Comments | P-value not adjusted for multiple comparisons. | |
| Method | ANCOVA | |
| Comments | P-value estimated using ANCOVA model with treatment,age,& gender as factors & baseline positive PANAS score as a covariate. | |
| Title | Positive and Negative Affect Schedule (PANAS) Change From Baseline in Negative Score at Day 4 |
|---|---|
| Description | The PANAS comprises two mood scales, one that measures positive affect and the other that measures negative affect. Subjects completing the PANAS are required to respond to a 20-item test using 5-point scale that ranges from very slightly or not at all (1) to extremely (5).Negative affect scores can be obtained by adding up scores for items 2, 4, 6, 7, 8, 11, 13, 15, 18 and 20. The negative affect score can range from 10 to 50, with lower scores representing lower level of negative affect, or the extent to which the individual feels aversive mood states and general distress. This analysis outcome treated Item #2 as random missing data. |
| Time Frame | Day 4, Week 1 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full analysis set, Week 1.Item #2 was incorrectly listed as "Disinterested" instead of "Distressed".resulting in incorrect data for this item for the first 16 subjects. The PANAS data for the first 16 randomized subjects and in total 72 data points was identified and removed from the database. See stats analysis for further details. |
| Arm/Group Title | LFMS Sham | LFMS 20 Minutes | LFMS 60 Minutes |
|---|---|---|---|
| Arm/Group Description | For sham therapy, the device will be on; however, no magnetic field stimulation will be delivered. Low field magnetic stimulation (no magnetic field for sham) will be administered using a portable tabletop device capable of generating time-varying electromagnetic fields of LFMS. LFMS: Low field magnetic stimulation (1 kHz oscillating magnetic field) will be administered using a portable tabletop device capable of generating time-varying electromagnetic fields of LFMS. For sham therapy, the device will be on; however, no magnetic field stimulation will be delivered. | LFMS 20 minutes + Sham 40 min.Low field magnetic stimulation (1 kilohertz oscillating magnetic field) will be administered using a portable tabletop device capable of generating time-varying electromagnetic fields of LFMS. LFMS: Low field magnetic stimulation (1 kHz oscillating magnetic field) will be administered using a portable tabletop device capable of generating time-varying electromagnetic fields of LFMS. For sham therapy, the device will be on; however, no magnetic field stimulation will be delivered. | LFMS 60 minutes.Low field magnetic stimulation (1 kilohertz oscillating magnetic field) will be administered using a portable tabletop device capable of generating time-varying electromagnetic fields of LFMS. LFMS: Low field magnetic stimulation (1 kHz oscillating magnetic field) will be administered using a portable tabletop device capable of generating time-varying electromagnetic fields of LFMS. For sham therapy, the device will be on; however, no magnetic field stimulation will be delivered. |
| Measure Participants | 41 | 40 | 41 |
| Least Squares Mean (95% Confidence Interval) [units on a scale] |
-2.27
|
-3.57
|
-5.32
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | LFMS Sham, LFMS 60 Minutes |
|---|---|---|
| Comments | Due to item #2 error, analyses were done in the following manner to check robustness: All missing values including these 72 data points in item #2 were considered as random missing data (values posted in outcome measures). The 72 data points were removed & the negative score for affected subjects & visits were not calculated. The 72 data points were imputed using worst value imputation algorithm (using score =5 as extremely) while other random missing values imputed by average. | |
| Type of Statistical Test | Superiority | |
| Comments | Negative score is sum of 10 items: 2,4,6,7,8,11,13,15,18,20. | |
| Statistical Test of Hypothesis | p-Value | 0.0307 |
| Comments | P-value not adjusted for multiple comparisons. All missing values including the 72 data points in Item#2 were considered as random missing data. | |
| Method | ANCOVA | |
| Comments | P-value estimated using ANCOVA model with treatment, age, & gender as factors & baseline negative PANAS score as a covariate. | |
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | LFMS Sham, LFMS 20 Minutes |
|---|---|---|
| Comments | Due to item #2 error, analyses were done in the following manner to check robustness: All missing values including these 72 data points in item #2 were considered as random missing data (values posted in outcome measures). The 72 data points were removed & the negative score for affected subjects & visits were not calculated. The 72 data points were imputed using worst value imputation algorithm (using score =5 as extremely) while other random missing values imputed by average. | |
| Type of Statistical Test | Superiority | |
| Comments | Negative score is sum of 10 items: 2,4,6,7,8,11,13,15,18,20. | |
| Statistical Test of Hypothesis | p-Value | 0.3537 |
| Comments | P-value not adjusted for multiple comparisons. All missing values including the 72 data points in Item#2 were considered as random missing data. . | |
| Method | ANCOVA | |
| Comments | P-value estimated using ANCOVA model with treatment, age, & gender as factors & baseline negative PANAS score as a covariate. | |
| Title | Positive and Negative Affect Schedule (PANAS) Change From Baseline in Negative Score at Day 4 |
|---|---|
| Description | The PANAS comprises two mood scales, one that measures positive affect and the other that measures negative affect. Subjects completing the PANAS are required to respond to a 20-item test using 5-point scale that ranges from very slightly or not at all (1) to extremely (5).Negative affect scores can be obtained by adding up scores for items 2, 4, 6, 7, 8, 11, 13, 15, 18 and 20. The negative affect score can range from 10 to 50, with lower scores representing lower level of negative affect, or the extent to which the individual feels aversive mood states and general distress. This analysis outcome treated Incorrect Item #2 where Item #2 data was removed. |
| Time Frame | Day 4 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full analysis set, Week 1.Item #2 was incorrectly listed as "Disinterested" instead of "Distressed".resulting in incorrect data for this item for the first 16 subjects. The PANAS data for the first 16 randomized subjects and in total 72 data points was identified and removed from the database. See stats analysis for further details. |
| Arm/Group Title | LFMS Sham | LFMS 20 Minutes | LFMS 60 Minutes |
|---|---|---|---|
| Arm/Group Description | For sham therapy, the device will be on; however, no magnetic field stimulation will be delivered. Low field magnetic stimulation (no magnetic field for sham) will be administered using a portable tabletop device capable of generating time-varying electromagnetic fields of LFMS. LFMS: Low field magnetic stimulation (1 kHz oscillating magnetic field) will be administered using a portable tabletop device capable of generating time-varying electromagnetic fields of LFMS. For sham therapy, the device will be on; however, no magnetic field stimulation will be delivered. | LFMS 20 minutes + Sham 40 min.Low field magnetic stimulation (1 kilohertz oscillating magnetic field) will be administered using a portable tabletop device capable of generating time-varying electromagnetic fields of LFMS. LFMS: Low field magnetic stimulation (1 kHz oscillating magnetic field) will be administered using a portable tabletop device capable of generating time-varying electromagnetic fields of LFMS. For sham therapy, the device will be on; however, no magnetic field stimulation will be delivered. | LFMS 60 minutes.Low field magnetic stimulation (1 kilohertz oscillating magnetic field) will be administered using a portable tabletop device capable of generating time-varying electromagnetic fields of LFMS. LFMS: Low field magnetic stimulation (1 kHz oscillating magnetic field) will be administered using a portable tabletop device capable of generating time-varying electromagnetic fields of LFMS. For sham therapy, the device will be on; however, no magnetic field stimulation will be delivered. |
| Measure Participants | 41 | 40 | 41 |
| Least Squares Mean (95% Confidence Interval) [units on a scale] |
-2.95
|
-3.78
|
-5.58
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | LFMS Sham, LFMS 60 Minutes |
|---|---|---|
| Comments | Due to item #2 error, analyses were done in the following manner to check robustness: All missing values including these 72 data points in item #2 were considered as random missing data (values posted in outcome measures). The 72 data points were removed & the negative score for affected subjects & visits were not calculated. The 72 data points were imputed using worst value imputation algorithm (using score =5 as extremely) while other random missing values imputed by average. | |
| Type of Statistical Test | Superiority | |
| Comments | Negative score is sum of 10 items: 2,4,6,7,8,11,13,15,18,20. | |
| Statistical Test of Hypothesis | p-Value | 0.0848 |
| Comments | P-value not adjusted for multiple comparisons. All missing values including the 72 data points in Item#2 were treated where incorrect Item #2 data was removed. | |
| Method | ANCOVA | |
| Comments | P-value estimated using ANCOVA model with treatment, age, & gender as factors & baseline negative PANAS score as a covariate. | |
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | LFMS Sham, LFMS 20 Minutes |
|---|---|---|
| Comments | Due to item #2 error, analyses were done in the following manner to check robustness: All missing values including these 72 data points in item #2 were considered as random missing data (values posted in outcome measures). The 72 data points were removed & the negative score for affected subjects & visits were not calculated. The 72 data points were imputed using worst value imputation algorithm (using score =5 as extremely) while other random missing values imputed by average. | |
| Type of Statistical Test | Superiority | |
| Comments | Negative score is sum of 10 items: 2,4,6,7,8,11,13,15,18,20. | |
| Statistical Test of Hypothesis | p-Value | 0.5930 |
| Comments | P-value not adjusted for multiple comparisons. All missing values including the 72 data points in Item#2 were treated where Incorrect Item #2 data was removed. | |
| Method | ANCOVA | |
| Comments | P-value estimated using ANCOVA model with treatment, age, & gender as factors & baseline negative PANAS score as a covariate. | |
| Title | Positive and Negative Affect Schedule (PANAS) Change From Baseline in Negative Score at End of Week 1, Day 4 |
|---|---|
| Description | The PANAS comprises two mood scales, one that measures positive affect and the other that measures negative affect. Subjects completing the PANAS are required to respond to a 20-item test using 5-point scale that ranges from very slightly or not at all (1) to extremely (5).Negative affect scores can be obtained by adding up scores for items 2, 4, 6, 7, 8, 11, 13, 15, 18 and 20. The negative affect score can range from 10 to 50, with lower scores representing lower level of negative affect, or the extent to which the individual feels aversive mood states and general distress. This analysis outcome approach took Incorrect Item #2 and imputed using worst possible value. |
| Time Frame | Day 4, Week 1 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full analysis set, Week 1.Item #2 was incorrectly listed as "Disinterested" instead of "Distressed".resulting in incorrect data for this item for the first 16 subjects. The PANAS data for the first 16 randomized subjects and in total 72 data points was identified and removed from the database. See stats analysis for further details. |
| Arm/Group Title | LFMS Sham | LFMS 20 Minutes | LFMS 60 Minutes |
|---|---|---|---|
| Arm/Group Description | For sham therapy, the device will be on; however, no magnetic field stimulation will be delivered. Low field magnetic stimulation (no magnetic field for sham) will be administered using a portable tabletop device capable of generating time-varying electromagnetic fields of LFMS. LFMS: Low field magnetic stimulation (1 kHz oscillating magnetic field) will be administered using a portable tabletop device capable of generating time-varying electromagnetic fields of LFMS. For sham therapy, the device will be on; however, no magnetic field stimulation will be delivered. | LFMS 20 minutes + Sham 40 min.Low field magnetic stimulation (1 kilohertz oscillating magnetic field) will be administered using a portable tabletop device capable of generating time-varying electromagnetic fields of LFMS. LFMS: Low field magnetic stimulation (1 kHz oscillating magnetic field) will be administered using a portable tabletop device capable of generating time-varying electromagnetic fields of LFMS. For sham therapy, the device will be on; however, no magnetic field stimulation will be delivered. | LFMS 60 minutes.Low field magnetic stimulation (1 kilohertz oscillating magnetic field) will be administered using a portable tabletop device capable of generating time-varying electromagnetic fields of LFMS. LFMS: Low field magnetic stimulation (1 kHz oscillating magnetic field) will be administered using a portable tabletop device capable of generating time-varying electromagnetic fields of LFMS. For sham therapy, the device will be on; however, no magnetic field stimulation will be delivered. |
| Measure Participants | 41 | 40 | 41 |
| Least Squares Mean (95% Confidence Interval) [units on a scale] |
-2.29
|
-3.50
|
-5.36
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | LFMS Sham, LFMS 60 Minutes |
|---|---|---|
| Comments | Due to item #2 error, analyses were done in the following manner to check robustness: All missing values including these 72 data points in item #2 were considered as random missing data (values posted in outcome measures). The 72 data points were removed & the negative score for affected subjects & visits were not calculated. The 72 data points were imputed using worst value imputation algorithm (using score =5 as extremely) while other random missing values imputed by average. | |
| Type of Statistical Test | Superiority | |
| Comments | Negative score is sum of 10 items: 2,4,6,7,8,11,13,15,18,20. | |
| Statistical Test of Hypothesis | p-Value | 0.0307 |
| Comments | P-value not adjusted for multiple comparisons. All missing values including the 72 data points in Item#2 were treated where incorrect Item #2 data was imputed using worst possible value. | |
| Method | ANCOVA | |
| Comments | P-value estimated using ANCOVA model with treatment, age, & gender as factors & baseline negative PANAS score as a covariate. | |
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | LFMS Sham, LFMS 20 Minutes |
|---|---|---|
| Comments | Due to item #2 error, analyses were done in the following manner to check robustness: All missing values including these 72 data points in item #2 were considered as random missing data (values posted in outcome measures). The 72 data points were removed & the negative score for affected subjects & visits were not calculated. The 72 data points were imputed using worst value imputation algorithm (using score =5 as extremely) while other random missing values imputed by average. | |
| Type of Statistical Test | Superiority | |
| Comments | Negative score is sum of 10 items: 2,4,6,7,8,11,13,15,18,20. | |
| Statistical Test of Hypothesis | p-Value | 0.3907 |
| Comments | P-value not adjusted for multiple comparisons. All missing values including the 72 data points in Item#2 were treated where incorrect Item #2 data was imputed using worst possible value. | |
| Method | ANCOVA | |
| Comments | P-value estimated using ANCOVA model with treatment, age, & gender as factors & baseline negative PANAS score as a covariate. | |
Adverse Events
| Time Frame | Day 1- Day 42. Treatment-emergent events for Week 1 was defined as any Adverse Event (AE) that began on or after Day 1 treatment until the end of Day 7. Treatment-emergent AEs for Week 2 was defined as any AE that began on or after the Day 8 treatment until the end of Day 15 (not including the follow-up phase). | |||||||
|---|---|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | "# affected" for each tx group is the incidence count for each event occurring from Day 1-42. Day 8 Re-randomization per response to Wk 1 tx & original tx assignment creates a higher exposure to LFMS Sham in Week 2. The "# at risk" for each tx group is total number of unique subjects who received at least one dose of tx being summarized during either Wk 1 or Wk 2. | |||||||
| Arm/Group Title | LFMS Sham | LFMS 20 Minutes | LFMS 60 Minutes | LFMS 120 Min - Week 2 | ||||
| Arm/Group Description | For sham therapy, the device will be on; however, no magnetic field stimulation will be delivered. Low field magnetic stimulation (no magnetic field for sham) will be administered using a portable tabletop device capable of generating time-varying electromagnetic fields of LFMS. LFMS: Low field magnetic stimulation (1 kHz oscillating magnetic field) will be administered using a portable tabletop device capable of generating time-varying electromagnetic fields of LFMS. For sham therapy, the device will be on; however, no magnetic field stimulation will be delivered. | LFMS 20 minutes + Sham 40 min.Low field magnetic stimulation (1 kilohertz oscillating magnetic field) will be administered using a portable tabletop device capable of generating time-varying electromagnetic fields of LFMS. LFMS: Low field magnetic stimulation (1 kHz oscillating magnetic field) will be administered using a portable tabletop device capable of generating time-varying electromagnetic fields of LFMS. For sham therapy, the device will be on; however, no magnetic field stimulation will be delivered. | LFMS 60 minutes.Low field magnetic stimulation (1 kilohertz oscillating magnetic field) will be administered using a portable tabletop device capable of generating time-varying electromagnetic fields of LFMS. LFMS: Low field magnetic stimulation (1 kHz oscillating magnetic field) will be administered using a portable tabletop device capable of generating time-varying electromagnetic fields of LFMS. For sham therapy, the device will be on; however, no magnetic field stimulation will be delivered. | Week 2 subjects may be re-randomized to receive LFMS 120 minutes. Low field magnetic stimulation (1 kilohertz oscillating magnetic field) will be administered using a portable tabletop device capable of generating time-varying electromagnetic fields of LFMS. LFMS: Low field magnetic stimulation (1 kHz oscillating magnetic field) will be administered using a portable tabletop device capable of generating time-varying electromagnetic fields of LFMS. For sham therapy, the device will be on; however, no magnetic field stimulation will be delivered. | ||||
All Cause Mortality |
||||||||
| LFMS Sham | LFMS 20 Minutes | LFMS 60 Minutes | LFMS 120 Min - Week 2 | |||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/79 (0%) | 0/40 (0%) | 0/41 (0%) | 0/41 (0%) | ||||
Serious Adverse Events |
||||||||
| LFMS Sham | LFMS 20 Minutes | LFMS 60 Minutes | LFMS 120 Min - Week 2 | |||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/79 (0%) | 0/40 (0%) | 0/41 (0%) | 0/41 (0%) | ||||
Other (Not Including Serious) Adverse Events |
||||||||
| LFMS Sham | LFMS 20 Minutes | LFMS 60 Minutes | LFMS 120 Min - Week 2 | |||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 20/79 (25.3%) | 14/40 (35%) | 13/41 (31.7%) | 10/41 (24.4%) | ||||
| Ear and labyrinth disorders | ||||||||
| Tinnitus | 0/79 (0%) | 0 | 1/40 (2.5%) | 1 | 0/41 (0%) | 0 | 0/41 (0%) | 0 |
| Eye disorders | ||||||||
| Lacrimation increased | 0/79 (0%) | 0 | 0/40 (0%) | 0 | 1/41 (2.4%) | 1 | 0/41 (0%) | 0 |
| Gastrointestinal disorders | ||||||||
| Nausea | 1/79 (1.3%) | 1 | 1/40 (2.5%) | 1 | 1/41 (2.4%) | 1 | 0/41 (0%) | 0 |
| Abdominal pain | 1/79 (1.3%) | 1 | 0/40 (0%) | 0 | 0/41 (0%) | 0 | 0/41 (0%) | 0 |
| Diarrhoea | 3/79 (3.8%) | 3 | 0/40 (0%) | 0 | 0/41 (0%) | 0 | 0/41 (0%) | 0 |
| General disorders | ||||||||
| Fatigue | 1/79 (1.3%) | 1 | 2/40 (5%) | 2 | 1/41 (2.4%) | 1 | 1/41 (2.4%) | 1 |
| Pyrexia | 2/79 (2.5%) | 2 | 0/40 (0%) | 0 | 0/41 (0%) | 0 | 0/41 (0%) | 0 |
| Infections and infestations | ||||||||
| Gasrtoenteritis | 0/79 (0%) | 0 | 0/40 (0%) | 0 | 1/41 (2.4%) | 1 | 0/41 (0%) | 0 |
| Gasrtoenteritis viral | 0/79 (0%) | 0 | 0/40 (0%) | 0 | 1/41 (2.4%) | 1 | 0/41 (0%) | 0 |
| Nasopharyngitis | 2/79 (2.5%) | 2 | 0/40 (0%) | 0 | 0/41 (0%) | 0 | 0/41 (0%) | 0 |
| Upper respiratory tract infecrion | 1/79 (1.3%) | 1 | 0/40 (0%) | 0 | 1/41 (2.4%) | 1 | 1/41 (2.4%) | 1 |
| Cellulitis | 1/79 (1.3%) | 1 | 0/40 (0%) | 0 | 0/41 (0%) | 0 | 0/41 (0%) | 0 |
| Ear infection viral | 0/79 (0%) | 0 | 1/40 (2.5%) | 1 | 0/41 (0%) | 0 | 0/41 (0%) | 0 |
| Nasopharyngitis | 0/79 (0%) | 0 | 1/40 (2.5%) | 1 | 0/41 (0%) | 0 | 1/41 (2.4%) | 1 |
| Sinusitis | 0/79 (0%) | 0 | 1/40 (2.5%) | 1 | 0/41 (0%) | 0 | 0/41 (0%) | 0 |
| Injury, poisoning and procedural complications | ||||||||
| Contusion | 0/79 (0%) | 0 | 0/40 (0%) | 0 | 0/41 (0%) | 0 | 1/41 (2.4%) | 1 |
| Ligament sprain | 0/79 (0%) | 0 | 1/40 (2.5%) | 1 | 0/41 (0%) | 0 | 0/41 (0%) | 0 |
| Procedural headache | 0/79 (0%) | 0 | 1/40 (2.5%) | 2 | 0/41 (0%) | 0 | 0/41 (0%) | 0 |
| Procedural pain | 1/79 (1.3%) | 1 | 0/40 (0%) | 0 | 0/41 (0%) | 0 | 0/41 (0%) | 0 |
| Eye contusion | 0/79 (0%) | 0 | 0/40 (0%) | 0 | 0/41 (0%) | 0 | 1/41 (2.4%) | 1 |
| Traumatic arthropathy | 0/79 (0%) | 0 | 0/40 (0%) | 0 | 0/41 (0%) | 0 | 1/41 (2.4%) | 1 |
| Investigations | ||||||||
| Blood creatinine increased | 1/79 (1.3%) | 1 | 0/40 (0%) | 0 | 0/41 (0%) | 0 | 0/41 (0%) | 0 |
| Metabolism and nutrition disorders | ||||||||
| Vitamin B12 deficiency | 1/79 (1.3%) | 1 | 0/40 (0%) | 0 | 0/41 (0%) | 0 | 0/41 (0%) | 0 |
| Musculoskeletal and connective tissue disorders | ||||||||
| Neck pain | 0/79 (0%) | 0 | 1/40 (2.5%) | 1 | 0/41 (0%) | 0 | 0/41 (0%) | 0 |
| Pain in extremity | 0/79 (0%) | 0 | 1/40 (2.5%) | 1 | 0/41 (0%) | 0 | 0/41 (0%) | 0 |
| Musculoskeletal chest pain | 0/79 (0%) | 0 | 0/40 (0%) | 0 | 0/41 (0%) | 0 | 1/41 (2.4%) | 1 |
| Musculoskeletal pain | 0/79 (0%) | 0 | 0/40 (0%) | 0 | 0/41 (0%) | 0 | 1/41 (2.4%) | 1 |
| Muscle spasm | 0/79 (0%) | 0 | 0/40 (0%) | 0 | 0/41 (0%) | 0 | 1/41 (2.4%) | 1 |
| Nervous system disorders | ||||||||
| Headche | 7/79 (8.9%) | 10 | 6/40 (15%) | 7 | 4/41 (9.8%) | 4 | 4/41 (9.8%) | 6 |
| Somnolence | 0/79 (0%) | 0 | 1/40 (2.5%) | 1 | 0/41 (0%) | 0 | 0/41 (0%) | 0 |
| Head Discomfort | 0/79 (0%) | 0 | 0/40 (0%) | 0 | 0/41 (0%) | 0 | 1/41 (2.4%) | 1 |
| Dizziness | 1/79 (1.3%) | 1 | 1/40 (2.5%) | 1 | 3/41 (7.3%) | 3 | 1/41 (2.4%) | 2 |
| Psychiatric disorders | ||||||||
| Insomnia | 2/79 (2.5%) | 2 | 0/40 (0%) | 0 | 2/41 (4.9%) | 3 | 1/41 (2.4%) | 1 |
| Abnormal dreams | 0/79 (0%) | 0 | 0/40 (0%) | 0 | 0/41 (0%) | 0 | 1/41 (2.4%) | 1 |
| Agitation | 0/79 (0%) | 0 | 0/40 (0%) | 0 | 0/41 (0%) | 0 | 1/41 (2.4%) | 1 |
| Anxiety | 0/79 (0%) | 0 | 0/40 (0%) | 0 | 0/41 (0%) | 0 | 1/41 (2.4%) | 1 |
| Depression | 1/79 (1.3%) | 1 | 0/40 (0%) | 0 | 0/41 (0%) | 0 | 0/41 (0%) | 0 |
| Respiratory, thoracic and mediastinal disorders | ||||||||
| Oropharyngeal pain | 1/79 (1.3%) | 1 | 0/40 (0%) | 0 | 0/41 (0%) | 0 | 0/41 (0%) | 0 |
| Sinus congestion | 1/79 (1.3%) | 2 | 0/40 (0%) | 0 | 0/41 (0%) | 0 | 0/41 (0%) | 0 |
| Skin and subcutaneous tissue disorders | ||||||||
| Hair disorder | 0/79 (0%) | 0 | 0/40 (0%) | 0 | 1/41 (2.4%) | 1 | 0/41 (0%) | 0 |
| Pruritis | 0/79 (0%) | 0 | 0/40 (0%) | 0 | 1/41 (2.4%) | 1 | 0/41 (0%) | 0 |
| Vascular disorders | ||||||||
| Hypertension | 0/79 (0%) | 0 | 0/40 (0%) | 0 | 1/41 (2.4%) | 1 | 0/41 (0%) | 0 |
Limitations/Caveats
The study was not powered for secondary measures. Statistical significance for group-wise comparisons wasn't expected.
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
| Name/Title | Dr. Atul Pande, MD, Chief Medical Officer |
|---|---|
| Organization | Tal Medical |
| Phone | |
| apande@talmedical.com |
Responsible Party:
Tal Medical, Inc.
ClinicalTrials.gov Identifier:
NCT02452892
Other Study ID Numbers:
- TAL-02-007
First Posted:
May 25, 2015
Last Update Posted:
Dec 5, 2017
Last Verified:
Sep 1, 2017