Effect of CES on Parasympathetic Tone

Sponsor
Weill Medical College of Cornell University (Other)
Overall Status
Completed
CT.gov ID
NCT02163967
Collaborator
Fisher Wallace Laboratories (Industry)
21
1
6
2.1
10.1

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
  • Device: Cranial Electrical Stimulation Fisher-Wallace Stimulator (Model FW100)
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

Study Type:
Interventional
Actual Enrollment :
21 participants
Allocation:
Randomized
Intervention Model:
Crossover Assignment
Masking:
Double (Participant, 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.
Primary Purpose:
Basic Science
Official Title:
Effect of Cranial Electrical Stimulation (CES) on Autonomic Regulation
Actual Study Start Date :
Jan 11, 2013
Actual Primary Completion Date :
Mar 15, 2013
Actual Study Completion Date :
Mar 15, 2013

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:
  • Fisher-Wallace Stimulator (Model FW100)
  • 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:
  • Fisher-Wallace Stimulator (Model FW100)
  • 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:
  • Fisher-Wallace Stimulator (Model FW100)
  • 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:
  • Fisher-Wallace Stimulator (Model FW100)
  • 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:
  • Fisher-Wallace Stimulator (Model FW100)
  • 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:
  • Fisher-Wallace Stimulator (Model FW100)
  • Outcome Measures

    Primary Outcome Measures

    1. 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

    1. 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

    2. 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

    3. 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

    Ages Eligible for Study:
    18 Years to 65 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    Yes
    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.
    Responsible Party:
    Weill Medical College of Cornell University
    ClinicalTrials.gov Identifier:
    NCT02163967
    Other Study ID Numbers:
    • WCMC1209013001
    First Posted:
    Jun 16, 2014
    Last Update Posted:
    Oct 11, 2019
    Last Verified:
    Oct 1, 2019
    Studies a U.S. FDA-regulated Drug Product:
    No
    Studies a U.S. FDA-regulated Device Product:
    Yes
    Product Manufactured in and Exported from the U.S.:
    Yes
    Keywords provided by Weill Medical College of Cornell University

    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

    1. Primary Outcome
    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.
    2. Secondary Outcome
    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
    3. Secondary Outcome
    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.
    4. Secondary Outcome
    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

    [Not Specified]

    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
    Email maltemus@med.cornell.edu
    Responsible Party:
    Weill Medical College of Cornell University
    ClinicalTrials.gov Identifier:
    NCT02163967
    Other Study ID Numbers:
    • WCMC1209013001
    First Posted:
    Jun 16, 2014
    Last Update Posted:
    Oct 11, 2019
    Last Verified:
    Oct 1, 2019