Non-invasive Vagal Nerve Stimulation to Improve Functional Outcomes in Veterans With Alcohol Use Disorder
Overview
- Phase
- Phase 1
- Intervention
- Not specified
- Conditions
- Alcohol Use Disorder
- Sponsor
- VA Office of Research and Development
- Enrollment
- 19
- Locations
- 1
- Primary Endpoint
- Measurement of Feasibility - Subject Retention (Number/Percentage of Subjects Who Return for a Follow-up Visit)
- Status
- Completed
- Last Updated
- 10 months ago
Overview
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.
Investigators
Eligibility Criteria
Inclusion Criteria
- •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 exclusion criteria: cardiac pacemaker, metal fragments in eyes/skin/body, aortic/aneurysm clips, heart-valve replacement, copper intrauterine device, shunt (ventricular or spinal), neuro/bio-stimulators
- •Vagus nerve stimulation related criteria: history of carotid endarterectomy, severe carotid artery disease (e.g., history of transient ischemic attack (TIA) or stroke\], congestive heart failure, cardiac arrhythmia, known severe coronary artery disease or recent myocardial infarction (within 5 years), history of seizure or syncope (within past year), prior neck surgery.
Outcomes
Primary Outcomes
Measurement of Feasibility - Subject Retention (Number/Percentage of Subjects Who Return for a Follow-up Visit)
Time Frame: 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.
Measurement of Feasibility - Serious Adverse Side Effects
Time Frame: 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).
Measurement of Feasibility - Recruitment Goal (Data Reflects the Number of Participants Who Were Successfully Enrolled in the Study)
Time Frame: 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.
Treatment Acceptability Questionnaire (TAQ)
Time Frame: 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 - Treatment Adherence (Number of Times Subjects Self-administered nVNS/Sham Stimulation for 7 Days as Instructed)
Time Frame: 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.
Secondary Outcomes
- Alcohol Urge Questionnaire (AUQ)(Baseline to week 1 of 2x daily intervention)
- Substance Use Recovery Evaluator (SURE)(Baseline to week 1 of 2x daily intervention)
- WHO Quality of Life Assessment (WHOQOL-BREF) - Psychological Domain(Baseline to week 1 of 2x daily intervention)
- Beck Anxiety Inventory (BAI)(Baseline to week 1 of 2x daily intervention)
- PROMIS Pain Interference(Baseline to week 1 of 2x daily intervention)