Alcohol Use Disorder
Conditions
Keywords
alcohol use disorder, neuromodulation, neuroimaging, withdrawal, anxiety, autonomic nervous system
Brief summary
Alcohol use disorder (AUD) is a major health concern amongst Veterans as it causes functional impairments and decreased quality of life. Current AUD treatments show limited effectiveness in reducing withdrawal-related psychological and physical distress, which drives the urge to drink to relieve these symptoms. The investigators propose the vagus nerve, which is the primary nerve of the "rest and digest" branch of the autonomic nervous system via its bidirectional connections between the brain and the body, as a novel treatment target for AUD. The goal of this study is to assess treatment efficacy and mechanism of action. Noninvasive neuromodulation technologies offer the possibility for innovative, low risk treatments to support the rehabilitation and community reintegration of Veterans with AUD.
Detailed description
Alcohol use disorder (AUD) is a serious mental health disorder that affects more than 40% of US military Veterans, presenting a major burden to this population and to the VA Healthcare System. 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 different treatment targets. Long-term excessive drinking results in homeostatic dysregulation due to changes in the central and autonomic nervous system, which manifests in psychological and physical distress during abstinence and results in the urge to drink to relieve these symptoms. These symptoms, which can be equated to withdrawal, lead to continued harmful drinking and relapse, and are associated with significant functional impairment and reduced quality of life. Current AUD treatments do not effectively mitigate this homeostatic dysregulation and have risks and side effects as well as other limitations. The investigators propose the vagus nerve, which is the main nerve of the parasympathetic branch of the autonomic nervous system and plays an important role in maintaining and restoring physiological homeostasis, as a novel treatment target for AUD. Noninvasive stimulation of the vagus nerve (nVNS) has been shown to alleviate anxiety, depression, and pain. The investigators hypothesize that nVNS can restore homeostasis and reduce withdrawal-related distress and craving, and consequently improve functional outcomes and quality of life in Veterans with AUD. The goal of this study is to assess treatment efficacy and mechanism of action. The proposed study will include 80 Veterans with current AUD, who will be randomized to receive nVNS or sham stimulation prior to performing a well-validated heat pain task designed to assess neural and physiological correlates of distress. 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 psychological and physiological distress, craving, and functional outcomes will be administered at baseline and post-treatment, as well as at a 1-month follow-up visit.
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 devices look identical to active devices and participants will undergo identical training for self-administration on upper anterior cervical area (overlying carotid artery). Sham devices do 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
Devices will be masked to ensure both the research team involved in data collection and participants are blinded (double-blind study design). An unblinded member of the research team, 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
Participants will be randomly assigned to receive either active or placebo stimulation, and will receive identical instructions on use of the device. Participants will remain in the same condition assigned at baseline and will be instructed to self-administer nVNS/sham at home for 7 days (2 mins bilaterally, 2x per day) and return for a follow-up visit. Stimulation will be administered by the examiner during a functional MRI scan during the baseline and the follow-up visit.
Eligibility
Sex/Gender
ALL
Age
21 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
1. Veterans between 21 and 65 years, any race or ethnicity. 2. Meet current DSM-5 diagnosis of moderate or severe AUD (Structured Clinical Interview for DMS-5 (SCID) interview) with at least one functional disability due to alcohol use, current alcohol craving, and current heavy drinking (\>= 5 drinks (men) / \>= 4 drinks (women) on the same occasion, on 5 or more days in the past month) as defined by the Substance Abuse and Mental Health Services Administration (SAMHSA), and mild to moderate withdrawal symptoms during abstinence. 3. Able to forgo consumption of alcohol for 12-24 hours without any serious discomfort or complications. 4. Capable of complying with study schedule, procedures, and speaks English. 5. Able to provide voluntary written informed consent prior to initiation of visit 1. 6. Able and willing to self-administer nVNS/sham stimulation as instructed for the duration of the study, and willing to commit to the return visit at the end of the study.
Exclusion criteria
1. Clinical Institute Withdrawal Assessment of Alcohol Scale (CIWA-Ar) score \>10 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). 2. Recent history past 6 months) of severe complications due to alcohol withdrawal (alcohol withdrawal seizures, hallucinations/illusions, delirium tremens). 3. Currently or recently (within last 90 days) enrolled in abstinence-based treatment program. 4. Evidence of a maladaptive pattern of substance use or abuse other than alcohol one month prior to screening visit. 5. Uncontrolled severe psychiatric disorder with psychotic symptoms or cognitive impairment. We will not exclude for PTSD. 6. At risk for suicide requiring urgent higher-level care or homicide (based on the Columbia-Suicide Severity Rating Scale and follow-up clinical interview). 7. History of neurological disorder that might be associated with cognitive dysfunction. 8. History of head trauma involving loss of consciousness \>24 hours 9. Clinically significant uncontrolled/unstable medical illness or clinically significant surgery within 1 month of the screening visit. 10. MRI-related
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Hamilton Anxiety Rating Scale (HAM-A) | Baseline to week 1 and 1 month post baseline of 2x daily intervention | The HAM-A is a 14-item scale that assesses the presence and severity of psychological distress and negative emotional states. Completion takes 10 minutes. This instrument is widely used in clinical trials and alcohol studies and is sensitive to both nVNS and AUD treatment. Items are rated on a scale ranging from 0 (not present) to 4 (very severe). |
| Clinical Institute Withdrawal Assessment of Alcohol Scale, Revised (CIWA-Ar) | Baseline to week 1 and 1 month post baseline of 2x daily intervention | The Clinical Institute Withdrawal Assessment of Alcohol Scale, Revised (CIWA-Ar) is a short form (5 min.) to assess symptoms of acute alcohol withdrawal and physical discomfort. The CIWA-Ar includes 8 items, 7 of which are rated from 1 to 7 (higher score indicating higher severity) and 1 of which is rated from 0 to 4 (higher score indication less orientation to place/or person) |
| Alcohol Urge Questionnaire (AUQ) | Baseline to week 1 and 1 month post baseline 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. Higher scores reflect greater craving. |
| WHO Quality of Life assessment (WHOQOL-BREF) | Baseline to week 1 and 1 month post baseline of 2x daily intervention | The WHOQOL-BREF assesses quality of life across four domains (physical health, psychological, social relationships, and environment) with a total of 26 questions. The WHOQOL-BREF is a widely used instrument with strong psychometric properties. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Neural response to heat pain fMRI task | Baseline to week 1 of 2x daily intervention | During this task, participants receive brief thermal stimuli (experienced temperature ranging from warm to hot) applied to the leg via a thermode. Neural activation will be measured using percent signal change with higher scores indicating greater activation. |
Countries
United States
Contacts
CONTACTRuth Klaming, PhD
PRINCIPAL_INVESTIGATORRuth Klaming, PhD
VA San Diego Healthcare System, San Diego, CA
Outcome results
None listed