Effect of CES on Parasympathetic Tone
Study Details
Study Description
Brief Summary
The hypothesis is that CES stimulation will dose dependently increase parasympathetic tone. Healthy subjects will have three 20 minute sessions of CES stimulation, at three different intensities of stimulation, with each session occurring on a separate day. Effect on parasympathetic tone will determined by measuring high frequency heart rate variability before, during and after the stimulation. The Fisher Wallace Stimulator (FW100) which delivers a low dose alternating current a varying frequencies will be used for the stimulation.
Condition or Disease | Intervention/Treatment | Phase |
---|---|---|
|
Phase 4 |
Detailed Description
Healthy subjects will have three 20 minute sessions of bitemporal CES stimulation, at three different intensities of stimulation (sham, 1 milli Amp, 2 milli Amp), with each session occurring on a separate day. The Fisher Wallace Stimulator (FW100) which delivers a low dose alternating current a varying pulsed frequencies (5 Hertz, 500 Hertz, and 25000 Hertzz) will be used for the stimulation. ECG will be recorded continuously for 15 minutes before stimulation, during 20 minute stimulation and for 15 minutes following stimulation. Effect on parasympathetic tone will determined by measuring high frequency heart rate variability before, during and after the stimulation. Effect of CES of heart rate and low frequency heart rate variability will also be examined. Subject side effects will also be assessed.
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
---|---|
Other: Dose sequence: Sham, Low, High Cranial Electrical Stimulation with Fisher-Wallace Stimulator (Model FW100) for 20 minutes on 3 separate days. Day 1- Sham stimulation; Day 2 -1 milliamp stimulation intensity, Day 3 - 2milliamp stimulation intensity |
Device: Cranial Electrical Stimulation Fisher-Wallace Stimulator (Model FW100)
low voltage alternating current transcranial electrical stimulation
Other Names:
|
Other: Dose sequence: Sham, High, Low Cranial Electrical Stimulation with Fisher-Wallace Stimulator (Model FW100) for 20 minutes on 3 separate days. Day 1- Sham stimulation; Day 2 -2 milliamp stimulation intensity, Day 3 - 1milliamp stimulation intensity |
Device: Cranial Electrical Stimulation Fisher-Wallace Stimulator (Model FW100)
low voltage alternating current transcranial electrical stimulation
Other Names:
|
Other: Dose sequence: Low, Sham, High Cranial Electrical Stimulation with Fisher-Wallace Stimulator (Model FW100) for 20 minutes on 3 separate days. Day 1- 1milliamp stimulation intensity; Day 2 -Sham stimulation; Day 3 - 2milliamp stimulation intensity |
Device: Cranial Electrical Stimulation Fisher-Wallace Stimulator (Model FW100)
low voltage alternating current transcranial electrical stimulation
Other Names:
|
Other: Dose sequence: Low, High, Sham Cranial Electrical Stimulation with Fisher-Wallace Stimulator (Model FW100) for 20 minutes on 3 separate days. Day 1- 1milliamp stimulation intensity; Day 2 - 2milliamp stimulation intensity; Day 3 - Sham stimulation |
Device: Cranial Electrical Stimulation Fisher-Wallace Stimulator (Model FW100)
low voltage alternating current transcranial electrical stimulation
Other Names:
|
Other: Dose sequence: High, Sham, Low Cranial Electrical Stimulation with Fisher-Wallace Stimulator (Model FW100) for 20 minutes on 3 separate days. Day 1- 2 milliamp stimulation intensity; Day 2 - Sham stimulation; Day 3 - 1 milliamp stimulation intensity |
Device: Cranial Electrical Stimulation Fisher-Wallace Stimulator (Model FW100)
low voltage alternating current transcranial electrical stimulation
Other Names:
|
Other: Dose sequence: High, Low, Sham Cranial Electrical Stimulation with Fisher-Wallace Stimulator (Model FW100) for 20 minutes on 3 separate days. Day 1- 2 milliamp stimulation intensity; Day 2 - 1 milliamp stimulation intensity; Day 3 - Sham stimulation |
Device: Cranial Electrical Stimulation Fisher-Wallace Stimulator (Model FW100)
low voltage alternating current transcranial electrical stimulation
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Change in High Frequency Heart Rate Variability [Mean HRV is calculated for the 15 minutes of baseline, for the 20 minutes of stimulation and for the 15 minutes post stimulation]
High frequency heart rate variability (HRV) will be calculated over successive 5 minute intervals from continuous ECG recordings and reported on a log scale with a minimum of 0 and a maximum of 10. Higher scores represent more heart rate variability.
Secondary Outcome Measures
- Number of Subjects Reporting Light Flickering in Peripheral Vision Side Effect [one hour]
Subjects were asked to report any side effects of the stimulation. Of all side effects reported by subjects, only light flickering in peripheral vision was endorsed by enough subjects to allow statistical analysis
- Change in Heart Rate [Mean heart rate is calculated for the 15 minutes of baseline, for the 20 minutes of stimulation and for the 15 minutes post stimulation]
Heart rate will be calculated over successive 5 minute intervals from continuous ECG recordings. Higher scores represent faster heart rate
- Change in Low Frequency Heart Rate Variability [Low frequency heart rate variability is calculated for the 15 minutes of baseline, for the 20 minutes of stimulation and for the 15 minutes post stimulation]
Low frequency heart rate variability will be calculated over successive 5 minute intervals from continuous ECG recordings and reported on a log scale with a minimum of 0 and a maximum of 10. Higher scores represent more heart rate variability.
Eligibility Criteria
Criteria
Inclusion Criteria:
- healthy volunteer
Exclusion Criteria:
-
daily psychotropic medication,
-
use of beta blocker,
-
pacemaker,
-
other metal in body,
-
history of seizures
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
---|---|---|---|---|---|
1 | Weill Cornell Medical College | New York | New York | United States | 10065 |
Sponsors and Collaborators
- Weill Medical College of Cornell University
- Fisher Wallace Laboratories
Investigators
- Principal Investigator: Margaret Altemus, MD, Weill Medical College, Cornell University
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- WCMC1209013001
Study Results
Participant Flow
Recruitment Details | |
---|---|
Pre-assignment Detail |
Arm/Group Title | Dose Sequence: Sham, Low, High | Dose Sequence: Sham, High, Low | Dose Sequence: Low, Sham, High | Dose Sequence; Low, High, Sham | Dose Sequence: High, Sham, Low | Dose Sequence: High, Low, Sham |
---|---|---|---|---|---|---|
Arm/Group Description | Cranial Electrical Stimulation Fisher-Wallace Stimulator (Model FW100): for 20 minutes on 3 separate days. Day 1 - Sham stimulation, Day 2 - 1milliamp stimulation intensity, Day 3 - 2 milliamp stimulation intensity | Cranial Electrical Stimulation Fisher-Wallace Stimulator (Model FW100): for 20 minutes on 3 separate days. Day 1 - Sham stimulation, Day 2 - 2 milliamp stimulation intensity, Day 3 - 1 milliamp stimulation intensity | Cranial Electrical Stimulation Fisher-Wallace Stimulator (Model FW100): for 20 minutes on 3 separate days. Day 1 - 1 milliamp stimulation intensity , Day 2 - Sham stimulation, Day 3 - 2 milliamp stimulation intensity | Cranial Electrical Stimulation Fisher-Wallace Stimulator (Model FW100): for 20 minutes on 3 separate days. Day 1 - 1 milliamp stimulation intensity , Day 2 - 2 milliamp stimulation intensity, Day 3 - Sham stimulation | Cranial Electrical Stimulation Fisher-Wallace Stimulator (Model FW100): for 20 minutes on 3 separate days. Day 1 - 2 milliamp stimulation intensity , Day 2 - Sham stimulation, Day 3 - 1 milliamp stimulation intensity | Cranial Electrical Stimulation Fisher-Wallace Stimulator (Model FW100): for 20 minutes on 3 separate days. Day 1 - 2 milliamp stimulation intensity , Day 2 - 1 milliamp stimulation intensity, Day 3 - Sham stimulation |
Period Title: First Intervention/ Day 1 | ||||||
STARTED | 4 | 4 | 3 | 4 | 3 | 3 |
COMPLETED | 4 | 4 | 3 | 4 | 3 | 3 |
NOT COMPLETED | 0 | 0 | 0 | 0 | 0 | 0 |
Period Title: First Intervention/ Day 1 | ||||||
STARTED | 3 | 4 | 2 | 4 | 3 | 3 |
COMPLETED | 3 | 4 | 2 | 4 | 3 | 3 |
NOT COMPLETED | 0 | 0 | 0 | 0 | 0 | 0 |
Period Title: First Intervention/ Day 1 | ||||||
STARTED | 3 | 3 | 2 | 4 | 3 | 3 |
COMPLETED | 3 | 3 | 2 | 4 | 3 | 3 |
NOT COMPLETED | 0 | 0 | 0 | 0 | 0 | 0 |
Baseline Characteristics
Arm/Group Title | All Study Participants |
---|---|
Arm/Group Description | Cranial Electrical Stimulation Fisher-Wallace Stimulator (Model FW100): low voltage alternating current transcranial electrical stimulation, stimulation for 20 minutes on 3 separate days. Subjects were randomized to order of stimulation dose on the 3 days. |
Overall Participants | 18 |
Age (years) [Mean (Standard Deviation) ] | |
Mean (Standard Deviation) [years] |
47
(17)
|
Sex: Female, Male (Count of Participants) | |
Female |
14
77.8%
|
Male |
4
22.2%
|
Ethnicity (NIH/OMB) (Count of Participants) | |
Hispanic or Latino |
1
5.6%
|
Not Hispanic or Latino |
17
94.4%
|
Unknown or Not Reported |
0
0%
|
Race (NIH/OMB) (Count of Participants) | |
American Indian or Alaska Native |
0
0%
|
Asian |
0
0%
|
Native Hawaiian or Other Pacific Islander |
0
0%
|
Black or African American |
2
11.1%
|
White |
16
88.9%
|
More than one race |
0
0%
|
Unknown or Not Reported |
0
0%
|
Outcome Measures
Title | Change in High Frequency Heart Rate Variability |
---|---|
Description | High frequency heart rate variability (HRV) will be calculated over successive 5 minute intervals from continuous ECG recordings and reported on a log scale with a minimum of 0 and a maximum of 10. Higher scores represent more heart rate variability. |
Time Frame | Mean HRV is calculated for the 15 minutes of baseline, for the 20 minutes of stimulation and for the 15 minutes post stimulation |
Outcome Measure Data
Analysis Population Description |
---|
3 subjects who did not complete testing sessions at all 3 stimulation doses we not included in the final analysis |
Arm/Group Title | Sham Stimulation | Low Dose | High Dose |
---|---|---|---|
Arm/Group Description | Cranial Electrical Stimulation Fisher-Wallace Stimulator (Model FW100): sham stimulation for 20 minutes | Cranial Electrical Stimulation Fisher-Wallace Stimulator (Model FW100): for 20 minutes at 1 milliamp stimulation dose | Cranial Electrical Stimulation Fisher-Wallace Stimulator (Model FW100): for 20 minutes at 2 milliamp stimulation dose |
Measure Participants | 18 | 18 | 18 |
Baseline |
5.10
(0.40)
|
5.14
(0.36)
|
5.00
(0.43)
|
Stimulation |
5.12
(.25)
|
5.36
(.23)
|
5.44
(.27)
|
Post Stimulation |
5.12
(.36)
|
5.40
(.34)
|
5.46
(.35)
|
Statistical Analysis 1
Statistical Analysis Overview | Comparison Group Selection | Sham Stimulation, Low Dose, High Dose |
---|---|---|
Comments | The null hypothesis is that there is no difference in High frequency HRV after 20 minutes of stimulation or 15 minutes after cessation of stimulation at the low (1mAmp) or high (2mAmp) dose compared to sham stimulation | |
Type of Statistical Test | Other | |
Comments | ||
Statistical Test of Hypothesis | p-Value | <.02 |
Comments | Mixed effects regression model, a nested (within subject) random intercept for dose, fixed effects for age, dose, time and dose x time interaction. Significance level p=.05, Bonferonni correction was used for post-hoc tests. | |
Method | Regression, Linear | |
Comments | Post-hoc comparisons using least-square means. Kenward-Roger adjustments to denominator degrees of freedom.Increase in HRV at 2Amp compared to sham. |
Title | Number of Subjects Reporting Light Flickering in Peripheral Vision Side Effect |
---|---|
Description | Subjects were asked to report any side effects of the stimulation. Of all side effects reported by subjects, only light flickering in peripheral vision was endorsed by enough subjects to allow statistical analysis |
Time Frame | one hour |
Outcome Measure Data
Analysis Population Description |
---|
All 21 subjects who completed at least one of the stimulation study visits are included in this analysis |
Arm/Group Title | Sham | Low Dose | High Dose |
---|---|---|---|
Arm/Group Description | Cranial Electrical Stimulation Fisher-Wallace Stimulator (Model FW100) sham stimulation for 20 minutes, once Cranial Electrical Stimulation Fisher-Wallace Stimulator (Model FW100): low voltage alternating current transcranial electrical stimulation | Cranial Electrical Stimulation Fisher-Wallace Stimulator (Model FW100) 1mAmp stimulation for 20 minutes, once Cranial Electrical Stimulation Fisher-Wallace Stimulator (Model FW100): low voltage alternating current transcranial electrical stimulation | Cranial Electrical Stimulation Fisher-Wallace Stimulator (Model FW100) 2mAmp stimulation for 20 minutes, once Cranial Electrical Stimulation Fisher-Wallace Stimulator (Model FW100): low voltage alternating current transcranial electrical stimulation |
Measure Participants | 20 | 19 | 18 |
Number [participants] |
0
0%
|
8
NaN
|
12
NaN
|
Statistical Analysis 1
Statistical Analysis Overview | Comparison Group Selection | Sham Stimulation, Low Dose, High Dose |
---|---|---|
Comments | The null hypothesis is that there will be no difference in the number of side effects reported during either dose of stimulation compared to sham stimulation. Statistical differences were examined for light flickering in peripheral vision . Other side effects were reported by too few subjects to be analyzed statistically. | |
Type of Statistical Test | Other | |
Comments | ||
Statistical Test of Hypothesis | p-Value | <.001 |
Comments | ||
Method | Chi-squared | |
Comments |
Title | Change in Heart Rate |
---|---|
Description | Heart rate will be calculated over successive 5 minute intervals from continuous ECG recordings. Higher scores represent faster heart rate |
Time Frame | Mean heart rate is calculated for the 15 minutes of baseline, for the 20 minutes of stimulation and for the 15 minutes post stimulation |
Outcome Measure Data
Analysis Population Description |
---|
3 subjects who did not complete all 3 stimulation sessions were not included in the analysis |
Arm/Group Title | Sham | Low Dose | High Dose |
---|---|---|---|
Arm/Group Description | Cranial Electrical Stimulation Fisher-Wallace Stimulator (Model FW100) sham stimulation for 20 minutes, once Cranial Electrical Stimulation Fisher-Wallace Stimulator (Model FW100): low voltage alternating current transcranial electrical stimulation | Cranial Electrical Stimulation Fisher-Wallace Stimulator (Model FW100) 1mAmp stimulation for 20 minutes, once Cranial Electrical Stimulation Fisher-Wallace Stimulator (Model FW100): low voltage alternating current transcranial electrical stimulation | Cranial Electrical Stimulation Fisher-Wallace Stimulator (Model FW100) 2mAmp stimulation for 20 minutes, once Cranial Electrical Stimulation Fisher-Wallace Stimulator (Model FW100): low voltage alternating current transcranial electrical stimulation |
Measure Participants | 18 | 18 | 18 |
Baseline |
70.4
(1.4)
|
71.8
(2.1)
|
73.6
(1.8)
|
Stimulation |
69.4
(1.3)
|
70.1
(2.0)
|
71.4
(2.1)
|
Post Stimulation |
68.3
(1.2)
|
69.1
(1.8)
|
70.7
(1.8)
|
Statistical Analysis 1
Statistical Analysis Overview | Comparison Group Selection | Sham Stimulation, Low Dose, High Dose |
---|---|---|
Comments | ||
Type of Statistical Test | Other | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.81 |
Comments | Mixed effects regression model, a nested (within subject) random intercept for dose, fixed effects for age, dose, time and dose x time interaction. Significance level p=.05, Bonferonni correction was used for post-hoc tests. | |
Method | Regression, Linear | |
Comments | Post-hoc comparisons were made using least-square means. Kenward-Roger adjustments to denominator degrees of freedom. |
Title | Change in Low Frequency Heart Rate Variability |
---|---|
Description | Low frequency heart rate variability will be calculated over successive 5 minute intervals from continuous ECG recordings and reported on a log scale with a minimum of 0 and a maximum of 10. Higher scores represent more heart rate variability. |
Time Frame | Low frequency heart rate variability is calculated for the 15 minutes of baseline, for the 20 minutes of stimulation and for the 15 minutes post stimulation |
Outcome Measure Data
Analysis Population Description |
---|
3 enrolled subjects who did not complete all 3 stimulation sessions were not included in the analysis. |
Arm/Group Title | Sham | Low Dose | High Dose |
---|---|---|---|
Arm/Group Description | Cranial Electrical Stimulation Fisher-Wallace Stimulator (Model FW100) sham stimulation for 20 minutes, once Cranial Electrical Stimulation Fisher-Wallace Stimulator (Model FW100): low voltage alternating current transcranial electrical stimulation | Cranial Electrical Stimulation Fisher-Wallace Stimulator (Model FW100) 1mAmp stimulation for 20 minutes, once Cranial Electrical Stimulation Fisher-Wallace Stimulator (Model FW100): low voltage alternating current transcranial electrical stimulation | Cranial Electrical Stimulation Fisher-Wallace Stimulator (Model FW100) 2mAmp stimulation for 20 minutes, once Cranial Electrical Stimulation Fisher-Wallace Stimulator (Model FW100): low voltage alternating current transcranial electrical stimulation |
Measure Participants | 18 | 18 | 18 |
Baseline |
5.21
(0.21)
|
5.29
(0.33)
|
5.01
(0.34)
|
Stimulation |
5.34
(0.21)
|
5.29
(0.32)
|
5.18
(0.32)
|
Post-stimulation |
5.56
(0.21)
|
5.43
(0.30)
|
5.17
(0.29)
|
Statistical Analysis 1
Statistical Analysis Overview | Comparison Group Selection | Sham Stimulation, Low Dose, High Dose |
---|---|---|
Comments | ||
Type of Statistical Test | Other | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.47 |
Comments | Mixed effects regression model, a nested (within subject) random intercept for dose, fixed effects for age, dose, time and dose x time interaction. Significance level p=.05, Bonferonni correction was used for post-hoc tests. | |
Method | Regression, Linear | |
Comments | Post-hoc comparisons were made using least-square means. Kenward-Roger adjustments to denominator degrees of freedom. |
Adverse Events
Time Frame | 1 hour | |||||
---|---|---|---|---|---|---|
Adverse Event Reporting Description | Of the 21 subjects enrolled, 20 participated in the sham stimulation session, 19 participated in the low dose stimulation session and 18 participated in the high dose stimulation session. | |||||
Arm/Group Title | Sham | Low Dose | High Dose | |||
Arm/Group Description | Cranial Electrical Stimulation Fisher-Wallace Stimulator (Model FW100) sham stimulation for 20 minutes, once Cranial Electrical Stimulation Fisher-Wallace Stimulator (Model FW100): low voltage alternating current transcranial electrical stimulation | Cranial Electrical Stimulation Fisher-Wallace Stimulator (Model FW100) 1mAmp stimulation for 20 mintues, once Cranial Electrical Stimulation Fisher-Wallace Stimulator (Model FW100): low voltage alternating current transcranial electrical stimulation | Cranial Electrical Stimulation Fisher-Wallace Stimulator (Model FW100) 2mAmp stimulation for 20 minutes, once Cranial Electrical Stimulation Fisher-Wallace Stimulator (Model FW100): low voltage alternating current transcranial electrical stimulation | |||
All Cause Mortality |
||||||
Sham | Low Dose | High Dose | ||||
Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
Total | 0/20 (0%) | 0/19 (0%) | 0/18 (0%) | |||
Serious Adverse Events |
||||||
Sham | Low Dose | High Dose | ||||
Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
Total | 0/20 (0%) | 0/19 (0%) | 0/18 (0%) | |||
Other (Not Including Serious) Adverse Events |
||||||
Sham | Low Dose | High Dose | ||||
Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
Total | 1/20 (5%) | 11/19 (57.9%) | 12/18 (66.7%) | |||
Nervous system disorders | ||||||
light flickering | 0/20 (0%) | 0 | 8/19 (42.1%) | 8 | 12/18 (66.7%) | 12 |
itching or tingling of scalp | 1/20 (5%) | 1 | 5/19 (26.3%) | 5 | 3/18 (16.7%) | 3 |
Limitations/Caveats
More Information
Certain Agreements
All Principal Investigators ARE 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 | Margaret Altemus |
---|---|
Organization | Weill Cornell Medical College |
Phone | 646-209-6277 |
maltemus@med.cornell.edu |
- WCMC1209013001