Clinical trial NCT05226130: Non-invasive Vagal Nerve Stimulation in Alcohol Use Disorder
Official title: Non-invasive Vagal Nerve Stimulation to Improve Functional Outcomes in Veterans With Alcohol Use Disorder
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Alcohol Use Disorder
Keywords: alcohol use
neuromodulation
neuroimaging
withdrawal
anxiety
quality of life
Lead sponsor: VA Office of Research and Development
Sponsor class: FED
First posted: 2022-02-07
Enrollment: 19
Sex: MALE
Minimum age (years): 21
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
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).
Primary purpose: TREATMENT

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.

Eligibility criteria: 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 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.

Primary outcomes:
measure: Treatment Acceptability Questionnaire (TAQ)
timeFrame: Baseline to week 1 of 2x daily intervention (measure only administered at at study completion, i.e., 1 week after baseline)
measure: Measurement of feasibility - Recruitment goal
timeFrame: Baseline to week 1 of 2x daily intervention
measure: Measurement of feasibility - Treatment adherence
timeFrame: Baseline to week 1 of 2x daily intervention
measure: Measurement of feasibility - Subject retention
timeFrame: Baseline to week 1 of 2x daily intervention
measure: Measurement of feasibility - Adverse side effects
timeFrame: Baseline to week 1 of 2x daily intervention
Secondary outcomes:
measure: Substance Use Recovery Evaluator (SURE)
timeFrame: Baseline to week 1 of 2x daily intervention
measure: WHO Quality of Life assessment (WHOQOL-BREF)
timeFrame: Baseline to week 1 of 2x daily intervention
measure: Beck Anxiety Inventory (BAI)
timeFrame: Baseline to week 1 of 2x daily intervention
measure: PROMIS Pain Interference
timeFrame: Baseline to week 1 of 2x daily intervention
measure: Alcohol Urge Questionnaire (AUQ)
timeFrame: Baseline to week 1 of 2x daily intervention
Other outcomes:
measure: Heat pain fMRI task
timeFrame: Baseline to week 1 of 2x daily intervention
Locations:
city: San Diego
country: United States
facility: VA San Diego Healthcare System, San Diego, CA
state: California
Study officials:
affiliation: VA San Diego Healthcare System, San Diego, CA
name: Ruth Klaming, PhD
role: PRINCIPAL_INVESTIGATOR
References: