Clinical trial NCT03191266: Transcranial Magnetic Stimulation for the Treatment of Veterans With Alcohol Use Disorders
Official title: Transcranial Magnetic Stimulation for the Treatment of Veterans With Alcohol Use Disorders
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Alcohol Use Disorder
Keywords: repetitive transcranial magnetic stimulation
alcohol use disorder
neuroimaging
relapse
Veterans
Lead sponsor: VA Office of Research and Development
Sponsor class: FED
First posted: 2017-06-19
Enrollment: 49
Sex: ALL
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: A double-blind randomized clinical trial with two groups: Active rTMS Treatment Group (Active rTMS) - will receive four to five treatments (two treatments per day) each week for 2 weeks. Sham Control Treatment group (i.e., identical rTMS experimental procedure, but no active stimulation) will receive the same frequency and duration of rTMS sessions. The proposed rTMS protocol is consistent with the FDA approved treatment regimen employed for major depressive disorders.
Primary purpose: TREATMENT

Brief summary: At least 60% of Veterans with an alcohol use disorder will relapse within 6 months of treatment, irrespective of the type of treatment they receive. This indicates that currently available interventions for treating AUD in Veterans are not effective in helping them achieve long-term sobriety. Repetitive transcranial magnetic stimulation (rTMS) is a brain stimulation method that is at the forefront of innovative, non-invasive, and safe treatments for AUD. However, there have been no studies that specifically determined the effectiveness of rTMS treatment for Veterans with AUD. This project will evaluate the effectiveness of rTMS treatment in promoting long-term abstinence in Veterans suffering from AUD. Assisting Veterans in achieving long-term and sustained sobriety is critical because it is associated with the best medical, cognitive, psychiatric, and psychosocial recovery from AUD.

Detailed description: Due to COVID-19 restrictions, active recruiting was suspended 31MAR20. Recruitment resumed 1SEP21

The purpose of this study is to evaluate the efficacy of intermittent theta burst repetitive transcranial magnetic stimulation (rTMS) as a treatment for Veterans with an alcohol use disorder (AUD) to decrease the exceedingly high rate of relapse associated with this condition.

At least 60% of those with AUD will experience a major relapse period within 6 months of treatment, irrespective of the intervention (psychosocial and/or pharmacological) employed. Consequently, the high prevalence of AUD and relapse following treatment in Veterans is associated with substantial resource allocation and costs for the DVA Health Care System. Current pharmacological and psychosocial interventions demonstrate only a moderate level of efficacy, which is reflected in the high rate of relapse in AUD.

rTMS is a neurostimulation method that is at the forefront of innovative, non-invasive, and safe treatments for AUD, and the disorders that commonly co-occur with AUD. To reduce the high rate of relapse in Veterans with AUD, it is necessary for interventions to more effectively address the associated neurobiological dysfunction and salient co-occurring conditions. Accordingly, additional rigorously controlled studies are required to determine if intermittent theta burst rTMS is an effective treatment for Veterans with AUD.

Participants will be recruited from VA Palo Alto Health Care System (VAPAHCS) residential substance abuse treatment clinics A double-blind randomized clinical trial with two groups: Active rTMS Treatment Group (Active rTMS) - will receive five treatments (two treatments per day) per week for 2 weeks. Sham Control Treatment group (i.e., identical rTMS experimental procedure, but no active stimulation) will receive the same frequency and duration of rTMS sessions. The proposed rTMS protocol is consistent with the FDA approved treatment regimen employed for major depressive disorders at the VAPAHCS MIRECC. Magnetic resonance imaging (MR) will be completed pre and post rTMS treatment and used to localize the left DLPFC in each participant to optimize rTMS for this region. Active and Sham rTMS groups will complete predictive measures \[i.e., MR measures of anterior frontal glutamate level, blood flow, and tissue volume, diffusion tensor imaging, functional connectivity, task-based fMRI\] and other outcome measures (i.e., measures of craving, mood, anxiety, neurocognition) immediately pre- and post-completion of the 2 weeks of rTMS sessions. Genetic markers (i.e., brain derived neurotrophic factor plasma levels and polymorphisms) will also be collected. Neuroimaging and genetic measures are necessary to establish potential biomarkers for prediction of rTMS treatment response, which is requisite for therapeutic optimization. For the 6 months following completion of active or sham rTMS treatment, participants will be contacted monthly, via telephone or in person, to complete a brief standardized measure of alcohol and substance use, craving, and psychiatric symptomatology to assess for changes in these variables over the previous 30 days.

This project will deliver completely novel data on the efficacy of intermittent theta burst rTMS for Veterans with AUD during the first 6 months following treatment. Monitoring over the entire first 6 months following treatment is crucial, given relapse within the first 6 months of treatment is robustly related to poor psychosocial functioning over the ensuing 1-3 years. The ultimate goal of this proposal is provide treatment that more effectively promotes sustained abstinence in the Veteran with AUD, as extended abstinence is robustly associated with optimum biomedical, neuropsychological, psychiatric, and psychosocial recovery and functioning.

Eligibility criteria: Inclusion Criteria:

* The study will be open to male and females, regardless of race and ethnic origin, who are in active treatment for an alcohol use disorder (AUD).
* Meet Diagnostic and Statistical Manual of Mental Disorders, 5th Edition criteria for AUD, and alcohol is self-identified as primary substance of misuse.
* Actively in treatment at VA Palo Alto HCS Addiction Treatment Service, and able to read, verbalize understanding, and voluntarily sign the Informed Consent Form prior to participation in study procedures.
* Participants will be accepted if taking medications specifically for the treatment of MDD, cigarette smoking, or for other psychiatric conditions.

  * as long as the medications are not documented to lower seizure threshold
  * must be stable on any psychotropic medication for at least 1 month prior to enrollment
  * it would be clinically contraindicated to require participants to discontinue such medications for research.
* Participants will be abstinent from alcohol and non-prescribed substances for at least 7 consecutive days prior to active or sham rTMS and no participant demonstrates active acute withdrawal symptoms.

Exclusion Criteria:

Psychiatric:

* History of Schizophrenia Spectrum Disorders
* Bipolar Disorders
* A current substance use disorder that exceeds the severity of the AUD

  * based on DSM-5 diagnostic criteria
* Current use of an FDA approved medication for treatment of AUD, i.e.:

  * disulfiram
  * acamprosate
  * naltrexone
* Active current suicidal intent or plan

  * patients with a previous clinical flag for risk for suicide will be required to have an established safety plan involving their primary psychiatrist and the treatment team before entering the clinical trial
* Any form of previous rTMS or electroconvulsive treatment

Biomedical:

* Including but not limited to uncontrolled thyroid disease
* Unstable congestive heart failure
* Angina
* Other severe cardiac illness as defined by treatment regimen changes in the prior 3 months
* Cerebrovascular accident
* Cancer if \< 1 year since end of treatment
* Unstable diabetes
* COPD requiring oxygen supplementation
* Alzheimer's disease
* Parkinson's disease
* Any biomedical implants with ferromagnetic content
* Neurostimulation devices
* Cardiac pacemakers or any magnetic resonance contraindications
* Traumatic brain injury with self-reported or observed loss of consciousness \> 30 minutes
* Any primary or traumatically induced seizure disorder

General:

* Lack of fluency in English
* Wechsler Adult Reading Test below the 7th percentile, i.e.:

  * moderate or greater impairment in estimated general intelligence
* Females who are pregnant or actively attempting pregnancy

  * conservative exclusion for magnetic resonance research
* Current use of any medication or substance that is documented to lower seizure threshold or has been identified as a contraindication for rTMS treatment

Primary outcomes:
measure: Frequency of abstinence from alcohol and other substances
timeFrame: 6 months
Secondary outcomes:
measure: Glutamate concentration in the left dorsolateral prefrontal cortex (as measured with single voxel spectroscopy)
timeFrame: Baseline
measure: Volume in anterior frontal cortical regions (as measured with FreeSurfer)
timeFrame: Baseline
measure: Functional connectivity (as measured with resting state fMRI)
timeFrame: Baseline
measure: BDNF polymorphisms (as measured with TaqMan genotyping assays or similar assays)
timeFrame: Baseline
Other outcomes:
Locations:
city: Palo Alto
country: United States
facility: VA Palo Alto Health Care System, Palo Alto, CA
state: California
Study officials:
affiliation: VA Palo Alto Health Care System, Palo Alto, CA
name: Timothy C. Durazzo, PhD
role: PRINCIPAL_INVESTIGATOR
References: