Autonomic Nervous System Imbalance
Conditions
Keywords
cranial electrical stimulation, CES, heart rate variability, parasympathetic, Vagal
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.
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.
Interventions
DEVICECranial Electrical Stimulation Fisher-Wallace Stimulator (Model FW100)
low voltage alternating current transcranial electrical stimulation
Sponsors
Fisher Wallace Laboratories
Weill Medical College of Cornell University
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
DOUBLE (Subject, Outcomes Assessor)
Masking description
Individual calculating heart rate and heart rate variability from ECG recordings was blind to dose of stimulation. Individual collecting side effect information was not blind to dose of stimulation.
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
Yes
Inclusion criteria
* healthy volunteer
Exclusion criteria
* daily psychotropic medication, * use of beta blocker, * pacemaker, * other metal in body, * history of seizures
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| All Study Participants 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. | 18 |
| Total | 18 |
Baseline characteristics
| Characteristic | All Study Participants |
|---|---|
| Age, Continuous | 47 years STANDARD_DEVIATION 17 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 17 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 16 Participants |
| Sex: Female, Male Female | 14 Participants |
| Sex: Female, Male Male | 4 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 20 | 0 / 19 | 0 / 18 |
| other Total, other adverse events | 1 / 20 | 11 / 19 | 12 / 18 |
| serious Total, serious adverse events | 0 / 20 | 0 / 19 | 0 / 18 |
Outcome results
Primary
Change in High Frequency Heart Rate Variability
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
Population: 3 subjects who did not complete testing sessions at all 3 stimulation doses we not included in the final analysis
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Sham Stimulation | Change in High Frequency Heart Rate Variability | Stimulation | 5.12 Units on a Log Scale | Standard Error 0.25 |
| Sham Stimulation | Change in High Frequency Heart Rate Variability | Baseline | 5.10 Units on a Log Scale | Standard Error 0.4 |
| Sham Stimulation | Change in High Frequency Heart Rate Variability | Post Stimulation | 5.12 Units on a Log Scale | Standard Error 0.36 |
| Low Dose | Change in High Frequency Heart Rate Variability | Stimulation | 5.36 Units on a Log Scale | Standard Error 0.23 |
| Low Dose | Change in High Frequency Heart Rate Variability | Baseline | 5.14 Units on a Log Scale | Standard Error 0.36 |
| Low Dose | Change in High Frequency Heart Rate Variability | Post Stimulation | 5.40 Units on a Log Scale | Standard Error 0.34 |
| High Dose | Change in High Frequency Heart Rate Variability | Baseline | 5.00 Units on a Log Scale | Standard Error 0.43 |
| High Dose | Change in High Frequency Heart Rate Variability | Post Stimulation | 5.46 Units on a Log Scale | Standard Error 0.35 |
| High Dose | Change in High Frequency Heart Rate Variability | Stimulation | 5.44 Units on a Log Scale | Standard Error 0.27 |
Comparison: 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 stimulationp-value: <0.02Regression, Linear
Secondary
Change in Heart Rate
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
Population: 3 subjects who did not complete all 3 stimulation sessions were not included in the analysis
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Sham Stimulation | Change in Heart Rate | Stimulation | 69.4 beats per minute | Standard Error 1.3 |
| Sham Stimulation | Change in Heart Rate | Baseline | 70.4 beats per minute | Standard Error 1.4 |
| Sham Stimulation | Change in Heart Rate | Post Stimulation | 68.3 beats per minute | Standard Error 1.2 |
| Low Dose | Change in Heart Rate | Stimulation | 70.1 beats per minute | Standard Error 2 |
| Low Dose | Change in Heart Rate | Baseline | 71.8 beats per minute | Standard Error 2.1 |
| Low Dose | Change in Heart Rate | Post Stimulation | 69.1 beats per minute | Standard Error 1.8 |
| High Dose | Change in Heart Rate | Baseline | 73.6 beats per minute | Standard Error 1.8 |
| High Dose | Change in Heart Rate | Post Stimulation | 70.7 beats per minute | Standard Error 1.8 |
| High Dose | Change in Heart Rate | Stimulation | 71.4 beats per minute | Standard Error 2.1 |
p-value: 0.81Regression, Linear
Secondary
Change in Low Frequency Heart Rate Variability
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
Population: 3 enrolled subjects who did not complete all 3 stimulation sessions were not included in the analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Sham Stimulation | Change in Low Frequency Heart Rate Variability | Stimulation | 5.34 Units on a Log Scale | Standard Error 0.21 |
| Sham Stimulation | Change in Low Frequency Heart Rate Variability | Baseline | 5.21 Units on a Log Scale | Standard Error 0.21 |
| Sham Stimulation | Change in Low Frequency Heart Rate Variability | Post-stimulation | 5.56 Units on a Log Scale | Standard Error 0.21 |
| Low Dose | Change in Low Frequency Heart Rate Variability | Stimulation | 5.29 Units on a Log Scale | Standard Error 0.32 |
| Low Dose | Change in Low Frequency Heart Rate Variability | Baseline | 5.29 Units on a Log Scale | Standard Error 0.33 |
| Low Dose | Change in Low Frequency Heart Rate Variability | Post-stimulation | 5.43 Units on a Log Scale | Standard Error 0.3 |
| High Dose | Change in Low Frequency Heart Rate Variability | Baseline | 5.01 Units on a Log Scale | Standard Error 0.34 |
| High Dose | Change in Low Frequency Heart Rate Variability | Post-stimulation | 5.17 Units on a Log Scale | Standard Error 0.29 |
| High Dose | Change in Low Frequency Heart Rate Variability | Stimulation | 5.18 Units on a Log Scale | Standard Error 0.32 |
p-value: 0.47Regression, Linear
Secondary
Number of Subjects Reporting Light Flickering in Peripheral Vision Side Effect
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
Population: All 21 subjects who completed at least one of the stimulation study visits are included in this analysis
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Sham Stimulation | Number of Subjects Reporting Light Flickering in Peripheral Vision Side Effect | 0 participants |
| Low Dose | Number of Subjects Reporting Light Flickering in Peripheral Vision Side Effect | 8 participants |
| High Dose | Number of Subjects Reporting Light Flickering in Peripheral Vision Side Effect | 12 participants |
Comparison: 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.p-value: <0.001Chi-squared