Alcohol Use Disorder
Conditions
Keywords
alcohol use, neuromodulation, neuroimaging, withdrawal, anxiety, quality of life
Brief summary
Alcohol use disorder (AUD) is a major health concern amongst Veterans as it causes poor health, lost days at work, impaired psychosocial functioning, and decreased quality of life. Current treatment options for AUD show limited effectiveness, which is exemplified by high relapse rates. Chronic heavy drinking results in psychological and physical distress during abstinence, including anxiety, irritability, and general discomfort, which increases the urge to drink to relieve these symptoms. The hypothesis of this study is that noninvasive vagal nerve stimulation (nVNS) can modify the perception of such inner bodily sensations of distress, and consequently reduces the drive to drink for relief. The aim of this study is to establish feasibility and acceptability of applying nVNS as a rehabilitative treatment for AUD in Veterans. The study will also evaluate the effect of nVNS on functional outcomes, quality of life, distress, and craving, and if nVNS alters neural activation patterns in brain regions involved in the perception and awareness of distress and pain.
Detailed description
AUD is a serious mental health disorder that affects more than 40% of US military Veterans, presenting a major burden to this population. Relapse rates of AUD are extremely high; over half of Veterans who complete treatment, relapse within 6 months, highlighting the need for improved treatments or differing treatment targets. Chronic, heavy drinking leads to an imbalance in homeostasis resulting in psychological and physical distress during periods of abstinence, and the urge to drink to relieve these symptoms to restore homeostasis. nVNS is a low-risk form of neuromodulation that has been shown to alleviate anxiety and chronic pain, and to reduce drug and alcohol relapse in animal models. The investigators hypothesize that nVNS attenuates distress-related craving in AUD in humans by modifying the autonomic nervous system and changing the perception of inner bodily sensations of physiological and affective distress. The investigators also hypothesize that nVNS improves functional outcomes and quality of life in Veterans with AUD. The proposed research will include 16 Veterans who meet for a diagnosis of AUD. Subjects will be randomly assigned to receive nVNS or sham stimulation prior to performing a well-validated functional Magnetic Resonance Imaging task designed to assess neural correlates of physical distress (via a heat stimulus). Subjects will then self-administer nVNS/sham at home twice a day for 7 days and return for a follow-up visit, during which all study components will be repeated. Behavioral assessments of functional disability, quality of life, psychological and physiological distress, and craving will be administered at baseline, after stimulation, and at follow-up. The aim of the proposed study is to establish feasibility and acceptability of applying nVNS as a rehabilitative treatment for AUD. In addition, the study will evaluate the preliminary effectiveness of nVNS in improving functional outcomes and quality of life, in reducing distress and craving, and in altering neural activation patterns in brain regions involved in the perception and awareness of distress and pain. The proposed work has the potential to lead to innovative, low-risk treatment options with high promise to significantly improve the care and lives of Veterans as there is a need for alternative treatments for AUD. As such, this novel AUD treatment could be particularly beneficial for Veterans who do not tolerate pharmacotherapy, and who have access or cognitive limitations or stigma concerns that act as barriers to psychotherapy.
Interventions
Active nVNS produces low-voltage electrical signal that generates sensations on the skin on upper anterior cervical area (overlying carotid artery) and that stimulates the vagus nerve.
Sham nVNS produces low-voltage electrical signal that generates sensations on the skin on upper anterior cervical area (overlying carotid artery) and that does not stimulate the vagus nerve.
Sponsors
VA Office of Research and Development
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Masking description
Both the research team involved in data collection and subjects will be blinded (double-blind study design). Subjects will be randomly assigned to receive either active or sham stimulation. Devices will be marked with an identification number to mask treatment condition. An unblinded Co-Investigator, not involved in data collection and subject contact, will assign randomization, provide device identification number, and keep the key linking condition to identification numbers.
Intervention model description
Devices include a sham and an active noninvasive vagal nerve stimulator (nVNS). Devices are identical in appearance, and both produce reliable sensation on the skin when applied to the neck area (transcutaneous cervical stimulation). Stimulation duration is approximately 120 seconds for both sham and active devices. Subjects receive the same instructions to self-administer stimulation twice a day for 120 minutes on each side (right and left).
Eligibility
Sex/Gender
MALE
Age
21 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Veteran * Male subjects between 21 and 65 years of age * Current DSM-5 diagnosis of AUD with at least one functional disability due to alcohol use, current alcohol craving, and current heavy drinking (\>4 drinks on any day or \>14 drinks per week) * Able to forgo consumption of alcohol for 24 hours without any serious discomfort including nausea/vomiting, visual/auditory/tactile hallucinations, or non-essential tremor
Exclusion criteria
* Clinical Institute Withdrawal Assessment of Alcohol Scale (CiWA) score \>=9 on the day of the scan (symptoms judged to be due to co-existing anxiety or headache disorders will not be counted toward the total). * Currently or recently (within last 90 days) enrolled in abstinence-based treatment program. * Evidence of a maladaptive pattern of substance use or abuse other than alcohol one month prior to screening visit. * Severe mental illness, e.g., psychosis or bipolar disorder * At risk for suicide or homicide * History of neurological disorder that might be associated with cognitive dysfunction. * History of head trauma involving loss of consciousness \>24 hours * Clinically significant uncontrolled/unstable medical illness or clinically significant surgery within 1 month of the screening visit. * MRI-related
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Measurement of Feasibility - Serious Adverse Side Effects | Baseline to week 1 of 2x daily intervention | Treatment feasibility will be evaluated by no occurrence of serious adverse side effects (as documented in checklist/daily log, interview at study completion, or otherwise reported by the participant). |
| Treatment Acceptability Questionnaire (TAQ) | Measure administered at study completion (i.e., 1 week after baseline) | The Treatment Acceptability Questionnaire (TAQ) is a self-rating questionnaire used to assess acceptability of a treatment. The TAQ uses a 7-point rating scale ranging from 1 to 7, with lower scores reflecting lower acceptability and a midpoint of 4 indicating neutral acceptability. A rating above the midpoint of the TAQ (i.e., score between 5 and 7) is the established criterion for acceptable to highly acceptable. |
| Measurement of Feasibility - Recruitment Goal (Data Reflects the Number of Participants Who Were Successfully Enrolled in the Study) | Baseline | Treatment feasibility will be evaluated by meeting the proposed recruitment goal of 16 Veterans within 12 months. This aim was measured as the number of study participants who signed the study consent form, completed at least the baseline study visit, and were included in the study analyses. |
| Measurement of Feasibility - Treatment Adherence (Number of Times Subjects Self-administered nVNS/Sham Stimulation for 7 Days as Instructed) | Baseline to week 1 of 2x daily intervention | Treatment adherence will be assessed via a daily treatment completion log, and calculated by dividing the total number of times subjects were instructed to self-administer the nVNS/sham stimulation (2x/day for 7 days = 14 times) by the number of times the subjects actually self-administered the stimulation. Treatment feasibility will be evaluated by meeting \>75% treatment adherence during the 1-week interval. |
| Measurement of Feasibility - Subject Retention (Number/Percentage of Subjects Who Return for a Follow-up Visit) | Baseline to post treatment, up to 21 days post baseline | Treatment feasibility will be evaluated by meeting \>75% subject retention at follow-up as measured by the number/percentage of subjects who return for a follow-up visit and complete primary outcome measures and return the device to the study team. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Alcohol Urge Questionnaire (AUQ) | Baseline to week 1 of 2x daily intervention | The Alcohol Urge Questionnaire (AUQ) is 8-item scale that measures cognitive preoccupation with alcohol on a 7-point rating scale ranging from strongly disagree to strongly agree. Two items are reverse scored. Minimum score is 8 and maximum is 56. Higher scores reflect greater craving. |
| Substance Use Recovery Evaluator (SURE) | Baseline to week 1 of 2x daily intervention | The Substance Use Recovery Evaluator (SURE) assesses the following domains of AUD-related functional outcomes: self-care (mental and physical health), relationships, material resources (stability of housing and occupational resources), and outlook of life. The SURE has been developed for use in substance use disorder populations. The SURE is comprised of 21 items, rated on a 3-point scale, but scored using a 3-point scale. Scores range from 21-63. A higher score indicates better functional outcomes. |
| WHO Quality of Life Assessment (WHOQOL-BREF) - Psychological Domain | Baseline to week 1 of 2x daily intervention | The WHO Quality of Life assessment (WHOQOL-BREF) assesses quality of life across four domains (physical health, psychological, social relationships, and environment) with a total of 26 questions. The rating scale ranges from 1 to 5 and minimum and maximum values varies between domains (physical health: 7-35, psychological: 6-30, social relationships: 3-15, environment: 8-40). Higher scores denote higher quality of life. Reported here are results from the psychological domain. |
| Beck Anxiety Inventory (BAI) | Baseline to week 1 of 2x daily intervention | The Beck Anxiety Inventory (BAI) is a self-report instrument to measure the severity of anxiety and emotional distress. The BAI is a 21-item questionnaire with a 4-point rating scale (0-3), with a higher score reflecting greater anxiety. Total scores range from 0 to 63 with higher scores indicating higher anxiety. |
| PROMIS Pain Interference | Baseline to week 1 of 2x daily intervention | The PROMIS Pain Interference measures self-reported consequences of pain on relevant aspects of one's life, i.e., the extent to which pain hinders engagement with social, cognitive, emotional, physical, and recreational activities. This questionnaire has 8 items with ratings ranging from not at all to very much. Total score minimum is 8 and the maximum is 40. Higher scores reflect higher interference of pain with level of functioning. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Neural Response to Heat Pain Stimuli (Measured as Sum of BOLD Beta Coefficients Over Time in Arbitrary Units) | Baseline to week 1 of 2x daily intervention | Participants receive brief thermal stimuli (experienced temperature ranging from warm to hot) applied to the leg via a contact thermode during a functional magnetic resonance imaging scan. Neural activation will be measured using the general linear model (GLM) to estimate beta coefficients for the BOLD (blood-oxygen-level-dependent) signal in response to thermal stimulation. Activation in the brain region insula will be summarized by calculating the area under the beta response curve (arbitrary units) over the stimulus duration (i.e., time), reflecting the total magnitude of neural activation. BOLD signal and beta coefficients used to model neural response are in arbitrary units. The area under the curve is the cumulative scaled beta (i.e., cumulative percent signal change) that is most reflective of the activation attributable to the stimulus. Higher numbers indicate more neural activation in the insula in response to painful heat stimuli. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Active Cervical Transcutaneous Vagus Nerve Stimulation Participants will be assigned to active transcutaneous vagus nerve stimulation, received once during each of the study visits and self-administered twice a day for a week.
Cervical transcutaneous vagus nerve stimulation (active comparator): Active nVNS produces low-voltage electrical signal that generates sensations on the skin on upper anterior cervical area (overlying carotid artery) and that stimulates the vagus nerve. | 9 |
| Sham Cervical Transcutaneous Vagus Nerve Stimulation Participants will be assigned to sham transcutaneous vagus nerve stimulation, received once during each of the study visits and self-administered twice a day for a week.
Cervical transcutaneous vagus nerve stimulation (sham comparator): Sham nVNS produces low-voltage electrical signal that generates sensations on the skin on upper anterior cervical area (overlying carotid artery) and that does not stimulate the vagus nerve. | 10 |
| Total | 19 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 0 | 1 |
| Overall Study | Not treatment adherent | 0 | 2 |
Baseline characteristics
| Characteristic | Sham Cervical Transcutaneous Vagus Nerve Stimulation | Total | Active Cervical Transcutaneous Vagus Nerve Stimulation |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 10 Participants | 19 Participants | 9 Participants |
| Age, Continuous | 39.6 years STANDARD_DEVIATION 7.2 | 38.6 years STANDARD_DEVIATION 7.8 | 37.4 years STANDARD_DEVIATION 8.6 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 2 Participants | 3 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 3 Participants | 2 Participants |
| Race (NIH/OMB) More than one race | 2 Participants | 2 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 4 Participants | 10 Participants | 6 Participants |
| Region of Enrollment United States | 10 Participants | 19 Participants | 9 Participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 10 Participants | 19 Participants | 9 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 9 | 0 / 10 |
| other Total, other adverse events | 4 / 9 | 1 / 10 |
| serious Total, serious adverse events | 0 / 9 | 0 / 10 |
Outcome results
Primary
Measurement of Feasibility - Recruitment Goal (Data Reflects the Number of Participants Who Were Successfully Enrolled in the Study)
Treatment feasibility will be evaluated by meeting the proposed recruitment goal of 16 Veterans within 12 months. This aim was measured as the number of study participants who signed the study consent form, completed at least the baseline study visit, and were included in the study analyses.
Time frame: Baseline
Population: More (19 subjects) than the initially proposed number of participants (16 subjects) were enrolled in the study.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Active Cervical Transcutaneous Vagus Nerve Stimulation | Measurement of Feasibility - Recruitment Goal (Data Reflects the Number of Participants Who Were Successfully Enrolled in the Study) | 9 Participants |
| Sham Cervical Transcutaneous Vagus Nerve Stimulation | Measurement of Feasibility - Recruitment Goal (Data Reflects the Number of Participants Who Were Successfully Enrolled in the Study) | 10 Participants |
Primary
Measurement of Feasibility - Serious Adverse Side Effects
Treatment feasibility will be evaluated by no occurrence of serious adverse side effects (as documented in checklist/daily log, interview at study completion, or otherwise reported by the participant).
Time frame: Baseline to week 1 of 2x daily intervention
Population: Number of serious adverse events
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Active Cervical Transcutaneous Vagus Nerve Stimulation | Measurement of Feasibility - Serious Adverse Side Effects | 0 Number of serious adverse events |
| Sham Cervical Transcutaneous Vagus Nerve Stimulation | Measurement of Feasibility - Serious Adverse Side Effects | 0 Number of serious adverse events |
Primary
Measurement of Feasibility - Subject Retention (Number/Percentage of Subjects Who Return for a Follow-up Visit)
Treatment feasibility will be evaluated by meeting \>75% subject retention at follow-up as measured by the number/percentage of subjects who return for a follow-up visit and complete primary outcome measures and return the device to the study team.
Time frame: Baseline to post treatment, up to 21 days post baseline
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Active Cervical Transcutaneous Vagus Nerve Stimulation | Measurement of Feasibility - Subject Retention (Number/Percentage of Subjects Who Return for a Follow-up Visit) | 9 Participants |
| Sham Cervical Transcutaneous Vagus Nerve Stimulation | Measurement of Feasibility - Subject Retention (Number/Percentage of Subjects Who Return for a Follow-up Visit) | 9 Participants |
Primary
Measurement of Feasibility - Treatment Adherence (Number of Times Subjects Self-administered nVNS/Sham Stimulation for 7 Days as Instructed)
Treatment adherence will be assessed via a daily treatment completion log, and calculated by dividing the total number of times subjects were instructed to self-administer the nVNS/sham stimulation (2x/day for 7 days = 14 times) by the number of times the subjects actually self-administered the stimulation. Treatment feasibility will be evaluated by meeting \>75% treatment adherence during the 1-week interval.
Time frame: Baseline to week 1 of 2x daily intervention
Population: 1 subject lost to FU
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Active Cervical Transcutaneous Vagus Nerve Stimulation | Measurement of Feasibility - Treatment Adherence (Number of Times Subjects Self-administered nVNS/Sham Stimulation for 7 Days as Instructed) | 94.4 percentage of treatment administrations | Standard Deviation 7.8 |
| Sham Cervical Transcutaneous Vagus Nerve Stimulation | Measurement of Feasibility - Treatment Adherence (Number of Times Subjects Self-administered nVNS/Sham Stimulation for 7 Days as Instructed) | 79.76 percentage of treatment administrations | Standard Deviation 26.4 |
Primary
Treatment Acceptability Questionnaire (TAQ)
The Treatment Acceptability Questionnaire (TAQ) is a self-rating questionnaire used to assess acceptability of a treatment. The TAQ uses a 7-point rating scale ranging from 1 to 7, with lower scores reflecting lower acceptability and a midpoint of 4 indicating neutral acceptability. A rating above the midpoint of the TAQ (i.e., score between 5 and 7) is the established criterion for acceptable to highly acceptable.
Time frame: Measure administered at study completion (i.e., 1 week after baseline)
Population: TAQ ratings for two subjects (both in the sham group) were not included in the analyses because they were not treatment adherent (i.e., did not self-administer nVNS/sham as instructed). One subject was lost to follow-up.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Active Cervical Transcutaneous Vagus Nerve Stimulation | Treatment Acceptability Questionnaire (TAQ) | 5.7 score on a scale | Standard Deviation 1 |
| Sham Cervical Transcutaneous Vagus Nerve Stimulation | Treatment Acceptability Questionnaire (TAQ) | 6.4 score on a scale | Standard Deviation 0.8 |
Secondary
Alcohol Urge Questionnaire (AUQ)
The Alcohol Urge Questionnaire (AUQ) is 8-item scale that measures cognitive preoccupation with alcohol on a 7-point rating scale ranging from strongly disagree to strongly agree. Two items are reverse scored. Minimum score is 8 and maximum is 56. Higher scores reflect greater craving.
Time frame: Baseline to week 1 of 2x daily intervention
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Active Cervical Transcutaneous Vagus Nerve Stimulation | Alcohol Urge Questionnaire (AUQ) | Baseline | 25.6 score on a scale | Standard Deviation 11.3 |
| Active Cervical Transcutaneous Vagus Nerve Stimulation | Alcohol Urge Questionnaire (AUQ) | Follow-up | 18.4 score on a scale | Standard Deviation 9.8 |
| Sham Cervical Transcutaneous Vagus Nerve Stimulation | Alcohol Urge Questionnaire (AUQ) | Baseline | 25.7 score on a scale | Standard Deviation 10.8 |
| Sham Cervical Transcutaneous Vagus Nerve Stimulation | Alcohol Urge Questionnaire (AUQ) | Follow-up | 21.2 score on a scale | Standard Deviation 8.3 |
Secondary
Beck Anxiety Inventory (BAI)
The Beck Anxiety Inventory (BAI) is a self-report instrument to measure the severity of anxiety and emotional distress. The BAI is a 21-item questionnaire with a 4-point rating scale (0-3), with a higher score reflecting greater anxiety. Total scores range from 0 to 63 with higher scores indicating higher anxiety.
Time frame: Baseline to week 1 of 2x daily intervention
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Active Cervical Transcutaneous Vagus Nerve Stimulation | Beck Anxiety Inventory (BAI) | Baseline | 16.8 score on a scale | Standard Deviation 9.2 |
| Active Cervical Transcutaneous Vagus Nerve Stimulation | Beck Anxiety Inventory (BAI) | Follow-up | 12.5 score on a scale | Standard Deviation 10 |
| Sham Cervical Transcutaneous Vagus Nerve Stimulation | Beck Anxiety Inventory (BAI) | Baseline | 17.0 score on a scale | Standard Deviation 11.6 |
| Sham Cervical Transcutaneous Vagus Nerve Stimulation | Beck Anxiety Inventory (BAI) | Follow-up | 17.6 score on a scale | Standard Deviation 17.8 |
Secondary
PROMIS Pain Interference
The PROMIS Pain Interference measures self-reported consequences of pain on relevant aspects of one's life, i.e., the extent to which pain hinders engagement with social, cognitive, emotional, physical, and recreational activities. This questionnaire has 8 items with ratings ranging from not at all to very much. Total score minimum is 8 and the maximum is 40. Higher scores reflect higher interference of pain with level of functioning.
Time frame: Baseline to week 1 of 2x daily intervention
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Active Cervical Transcutaneous Vagus Nerve Stimulation | PROMIS Pain Interference | Baseline | 22.4 score on a scale | Standard Deviation 8.3 |
| Active Cervical Transcutaneous Vagus Nerve Stimulation | PROMIS Pain Interference | Follow-up | 20.9 score on a scale | Standard Deviation 8.2 |
| Sham Cervical Transcutaneous Vagus Nerve Stimulation | PROMIS Pain Interference | Baseline | 23.6 score on a scale | Standard Deviation 9.7 |
| Sham Cervical Transcutaneous Vagus Nerve Stimulation | PROMIS Pain Interference | Follow-up | 21.8 score on a scale | Standard Deviation 11 |
Secondary
Substance Use Recovery Evaluator (SURE)
The Substance Use Recovery Evaluator (SURE) assesses the following domains of AUD-related functional outcomes: self-care (mental and physical health), relationships, material resources (stability of housing and occupational resources), and outlook of life. The SURE has been developed for use in substance use disorder populations. The SURE is comprised of 21 items, rated on a 3-point scale, but scored using a 3-point scale. Scores range from 21-63. A higher score indicates better functional outcomes.
Time frame: Baseline to week 1 of 2x daily intervention
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Active Cervical Transcutaneous Vagus Nerve Stimulation | Substance Use Recovery Evaluator (SURE) | Baseline | 44.7 score on a scale | Standard Deviation 7.8 |
| Active Cervical Transcutaneous Vagus Nerve Stimulation | Substance Use Recovery Evaluator (SURE) | Follow-up | 50.6 score on a scale | Standard Deviation 10.5 |
| Sham Cervical Transcutaneous Vagus Nerve Stimulation | Substance Use Recovery Evaluator (SURE) | Baseline | 44.0 score on a scale | Standard Deviation 5.7 |
| Sham Cervical Transcutaneous Vagus Nerve Stimulation | Substance Use Recovery Evaluator (SURE) | Follow-up | 44.9 score on a scale | Standard Deviation 8.8 |
Secondary
WHO Quality of Life Assessment (WHOQOL-BREF) - Psychological Domain
The WHO Quality of Life assessment (WHOQOL-BREF) assesses quality of life across four domains (physical health, psychological, social relationships, and environment) with a total of 26 questions. The rating scale ranges from 1 to 5 and minimum and maximum values varies between domains (physical health: 7-35, psychological: 6-30, social relationships: 3-15, environment: 8-40). Higher scores denote higher quality of life. Reported here are results from the psychological domain.
Time frame: Baseline to week 1 of 2x daily intervention
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Active Cervical Transcutaneous Vagus Nerve Stimulation | WHO Quality of Life Assessment (WHOQOL-BREF) - Psychological Domain | Baseline | 14.2 score on a scale | Standard Deviation 4.1 |
| Active Cervical Transcutaneous Vagus Nerve Stimulation | WHO Quality of Life Assessment (WHOQOL-BREF) - Psychological Domain | Follow-up | 16.8 score on a scale | Standard Deviation 4.4 |
| Sham Cervical Transcutaneous Vagus Nerve Stimulation | WHO Quality of Life Assessment (WHOQOL-BREF) - Psychological Domain | Baseline | 17.8 score on a scale | Standard Deviation 4 |
| Sham Cervical Transcutaneous Vagus Nerve Stimulation | WHO Quality of Life Assessment (WHOQOL-BREF) - Psychological Domain | Follow-up | 17.4 score on a scale | Standard Deviation 4.3 |
Other Pre-specified
Neural Response to Heat Pain Stimuli (Measured as Sum of BOLD Beta Coefficients Over Time in Arbitrary Units)
Participants receive brief thermal stimuli (experienced temperature ranging from warm to hot) applied to the leg via a contact thermode during a functional magnetic resonance imaging scan. Neural activation will be measured using the general linear model (GLM) to estimate beta coefficients for the BOLD (blood-oxygen-level-dependent) signal in response to thermal stimulation. Activation in the brain region insula will be summarized by calculating the area under the beta response curve (arbitrary units) over the stimulus duration (i.e., time), reflecting the total magnitude of neural activation. BOLD signal and beta coefficients used to model neural response are in arbitrary units. The area under the curve is the cumulative scaled beta (i.e., cumulative percent signal change) that is most reflective of the activation attributable to the stimulus. Higher numbers indicate more neural activation in the insula in response to painful heat stimuli.
Time frame: Baseline to week 1 of 2x daily intervention
Population: Two subjects did not participate in neuroimaging scans due to claustrophobia.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Active Cervical Transcutaneous Vagus Nerve Stimulation | Neural Response to Heat Pain Stimuli (Measured as Sum of BOLD Beta Coefficients Over Time in Arbitrary Units) | Baseline | -0.48 Arbitrary units | Standard Deviation 0.25 |
| Active Cervical Transcutaneous Vagus Nerve Stimulation | Neural Response to Heat Pain Stimuli (Measured as Sum of BOLD Beta Coefficients Over Time in Arbitrary Units) | Follow-up | -0.38 Arbitrary units | Standard Deviation 0.24 |
| Sham Cervical Transcutaneous Vagus Nerve Stimulation | Neural Response to Heat Pain Stimuli (Measured as Sum of BOLD Beta Coefficients Over Time in Arbitrary Units) | Follow-up | 1.00 Arbitrary units | Standard Deviation 1.21 |
| Sham Cervical Transcutaneous Vagus Nerve Stimulation | Neural Response to Heat Pain Stimuli (Measured as Sum of BOLD Beta Coefficients Over Time in Arbitrary Units) | Baseline | -0.37 Arbitrary units | Standard Deviation 0.27 |