PORT: Patient-oriented Randomized Pragmatic Feasibility Trial With rTMS in Depression and Anxiety

Sponsor

University of British Columbia (Other)

Overall Status

Recruiting

CT.gov ID

NCT05028738

Collaborator

(none)

100

Enrollment

Location

Arms

9.7

Anticipated Duration (Months)

10.4

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This trial compares intermittent theta-burst stimulation (iTBS) to low frequency repetitive transcranial magnetic stimulation (LFR) in regards to depression and anxiety outcomes in 100 patients with treatment resistant depression (TRD).

Condition or Disease	Intervention/Treatment	Phase
Major Depressive Episode Major Depressive Disorder	Device: Repetitive Transcranial Magnetic Stimulation	N/A

Detailed Description

The overarching goal of this trial is to evaluate whether a definite adaptive pragmatic trial would be feasible and establish clear go/no-go criteria as to whether proceeding to such definite trial is feasible. Specific aims include 1) testing the feasibility of recruiting a sample of TRD patients with less strict inclusion and exclusion criteria; 2) comparing different depression and anxiety scales (both clinician-rated and self-rated) and seek input from patients regarding their preferences; 3) seek input from patients with regards to the use of digital phenotyping as a tool to investigate biomarkers as well as engaging in the design of a potential implementation of such biomarker in a future definite trial.

Aim 1. To evaluate the feasibility of a future definite adaptive pragmatic RCT comparing left vs right DLPFC repetitive transcranial magnetic stimulation (rTMS) in TRD.

Hypothesis 1a: Enrollment will be 70% of the planned target over the 1-year recruitment period.

Hypothesis 1b: Retention rate of randomized participants will be ≥70% at the end of the intervention in both groups.

Aim 2. To evaluate patients' preferences regarding information about treatment options when there is no response to allocated treatment.

Hypothesis 2: Patients will prefer to modify treatment when there is no response.

Aim 3. To assess the feasibility of digital phenotyping as an tool to investigate biomarkers in TRD.

Hypothesis 3a: Survey uptake and participation in the study regarding the use of digital phenotyping will be 80% of randomized participants. Hypothesis 3b: Of those survey responders, 75% will indicate they would consent to digital phenotyping in a future definite RCT.

Aim 4. To develop a Bayesian statistical model that continuously updates personalized treatment effect estimates as the trial progresses, and identify the circumstances under which use of the model in a full-scale trial could inform treatment choice as the trial progresses.

Hypothesis 4: The modeling results will identify at least one subgroup for whom early stopping of the definitive trial in that subgroup may be warranted.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

100 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

Two-arm, randomized feasibility trialTwo-arm, randomized feasibility trial

Masking:

Double (Investigator, Outcomes Assessor)

Masking Description:

Single-masked (i.e. raters)

Primary Purpose:

Treatment

Official Title:

Patient-oriented Randomized Pragmatic Feasibility Trial With rTMS in Depression and Anxiety

Actual Study Start Date :

Oct 11, 2021

Anticipated Primary Completion Date :

Jul 1, 2022

Anticipated Study Completion Date :

Aug 1, 2022

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Intermittent Theta Burst Stimulation (iTBS) iTBS to the L-DLPFC	Device: Repetitive Transcranial Magnetic Stimulation rTMS will employ the MagPro X100 stimulator equipped with the cool-B70 coil (MagVenture, Farum, Denmark). The dose will be a 120% resting motor threshold (rMT) in accordance to our latest trial using iTBS. Localization of the right and left DLPFC will follow the well-established Beam F3 procedure. Subjects will then undergo 30 sessions of rTMS, once daily on weekdays for 6 weeks. FDA-approved iTBS protocol will consist of bursts of 3 pulses at 50 Hz, bursts repeated at 5 Hz for 600 pulses total, 2 s on, 8 s off, for 3 min 9 sec, at 120% rMT. LFR will consist of 1 Hz stimulation consisting of a single train of 10min duration for 600 pulses total at 120% rMT.
Active Comparator: Low Frequency Right (LFR) 1Hz stimulation to the R-DLPFC	Device: Repetitive Transcranial Magnetic Stimulation rTMS will employ the MagPro X100 stimulator equipped with the cool-B70 coil (MagVenture, Farum, Denmark). The dose will be a 120% resting motor threshold (rMT) in accordance to our latest trial using iTBS. Localization of the right and left DLPFC will follow the well-established Beam F3 procedure. Subjects will then undergo 30 sessions of rTMS, once daily on weekdays for 6 weeks. FDA-approved iTBS protocol will consist of bursts of 3 pulses at 50 Hz, bursts repeated at 5 Hz for 600 pulses total, 2 s on, 8 s off, for 3 min 9 sec, at 120% rMT. LFR will consist of 1 Hz stimulation consisting of a single train of 10min duration for 600 pulses total at 120% rMT.

Arm

Intervention/Treatment

Active Comparator: Intermittent Theta Burst Stimulation (iTBS)

iTBS to the L-DLPFC

Device: Repetitive Transcranial Magnetic Stimulation

rTMS will employ the MagPro X100 stimulator equipped with the cool-B70 coil (MagVenture, Farum, Denmark). The dose will be a 120% resting motor threshold (rMT) in accordance to our latest trial using iTBS. Localization of the right and left DLPFC will follow the well-established Beam F3 procedure. Subjects will then undergo 30 sessions of rTMS, once daily on weekdays for 6 weeks. FDA-approved iTBS protocol will consist of bursts of 3 pulses at 50 Hz, bursts repeated at 5 Hz for 600 pulses total, 2 s on, 8 s off, for 3 min 9 sec, at 120% rMT. LFR will consist of 1 Hz stimulation consisting of a single train of 10min duration for 600 pulses total at 120% rMT.

Active Comparator: Low Frequency Right (LFR)

1Hz stimulation to the R-DLPFC

Device: Repetitive Transcranial Magnetic Stimulation

Outcome Measures

Primary Outcome Measures

Depression severity [one week post treatment]
Inventory of Depressive Symptoms (IDS-30-SR); Minimum value per question: 0; Maximum value per question: 3; Total minimum value: 0; Total maximum value: 84; Higher score means worse outcome.

Secondary Outcome Measures

Suicidal ideation [one week post treatment]
Columbia-Suicide Severity Rating Scale (C-SSRS); This questionnaire has binary responses (Yes/No). More responses with "Yes" mean worse outcome.
Anxiety severity [one week post treatment]
Brief Symptom Inventory anxiety subscale (BSI-Anxiety); Minimum value per question: 0 (Not at all); Maximum value per question: 4 (Extremely); Total minimum value: 0; Total maximum value: 24; Higher score means worse outcome.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

are outpatients;
are voluntary and competent to consent to treatment;
are ≥ 18 years;
have a score ≥ 26 on the IDS-30-SR;
have had no increase or initiation of any psychotropic medication in the 4 weeks prior to screening;
able to adhere to the treatment schedule;
pass the TMS adult safety screening (TASS) questionnaire

Exclusion Criteria:

have active suicidal intent;
are pregnant;
have a lifetime diagnosis of schizophrenia, bipolar disorder type I, schizophreniform, schizoaffective disorder or presence of psychotic symptoms within last 3 months;
have a concomitant major unstable medical illness;
have any significant form of dementia or any history of epilepsy;
have any intracranial implant (e.g., aneurysm clips, shunts, stimulators, cochlear implants, or electrodes) or any other metal object within or near the head, excluding the mouth, that cannot be safely removed;
If participating in psychotherapy, must have been in stable treatment for at least 3 months prior to entry into the study, with no anticipation of change in the frequency of therapeutic sessions, or the therapeutic focus over the duration of the study;
If they are taking psychotropic medication, be on a stable dose for 4 weeks before starting treatment, and no initiation of new regular psychotropic medication;
have a clinically significant laboratory abnormality, in the opinion of the one of the principal investigators;
have a non-correctable clinically significant sensory impairment (i.e., cannot hear well enough to cooperate with interview).