Alcohol Use Disorder (AUD), Transcranial Magnetic Stimulation
Conditions
Keywords
Veterans, Deep Transcranial Magnetic Stimulation (dTMS), Alcohol Use Disorder, Neuroimaging, Relapse
Brief summary
This study aims to evaluate the efficacy of deep transcranial magnetic stimulation (dTMS) as a treatment for Veterans with an alcohol use disorder (AUD).
Detailed description
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 VA 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. TMS is a neurostimulation method that is at the forefront of innovative, non-invasive, and safe treatments for AUD, and other psychiatric disorders. To reduce the high rate of relapse in Veterans with AUD, it is necessary for interventions to more effectively address the associated neurobiological dysfunction. Non-invasive neuromodulation techniques are showing promise toward the aim of modifying specific and selective neural targets related to AUD and relapse. However, device-based interventions to date for AUD have focused on cortical stimulation. In contrast, preclinical and clinical studies, including our research team's preliminary data, suggest that subcortical nodes within the salience network could be promising novel neuromodulation targets. The dorsal anterior cingulate cortex (dACC) is a core node of the salience network, and hence the target of this proposal. Deep repetitive transcranial magnetic stimulation (dTMS) is one type of neuromodulation technique, and utilizing an H7 coil design can reach the dACC. Monitoring periodically throughout the 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 to 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.
Interventions
DEVICEDeep Transcranial Magnetic Stimulation (dTMS) H7 coil
The study will utilize the H7 coil to administer Deep Transcranial Magnetic Stimulation (dTMS) to the dorsal anterior cingulate cortex (dACC), a core salience network node.
Sponsors
VA Palo Alto Health Care System
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
21 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
* The study will be open to male and females, regardless of race and ethnic origin, 21-70 years of age, who are in active treatment for an AUD at the VAPAHCS, Foundations of Recovery. * Participants must meet Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5) criteria for AUD, and alcohol is self-identified as the primary substance of misuse. * Able to read, verbalize understanding, and voluntarily sign the Informed Consent Form prior to participation in study procedures in English. * Participants will be accepted if taking medications specifically for the treatment of major depressive disorders, cigarette smoking, or for other psychiatric conditions as long as the medications are not documented to lower seizure threshold - it would be clinically contraindicated to require participants to discontinue such medications for research. rTMS is safely administered to individuals who are taking psychotropic medications that do not lower seizure threshold. * Participants will be abstinent from alcohol and non-prescribed substances for at least 7 consecutive days prior to rTMS to ensure no participant is experiencing active acute withdrawal.
Exclusion criteria
Psychiatric: * Current diagnosis of Schizophrenia Spectrum Disorders and Bipolar Disorders; * Current moderate-severe substance use disorder other than alcohol, tobacco, or marijuana, based on DSM-5 diagnostic criteria; * 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, and alcohol-related seizure(s) in the past 30 days. 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Relapse to Alcohol 6 Months After Treatment | 6 months | Six months after completing the intervention, participants will be contacted to determine self-reported relapse status. To determine relapse status, participants complete brief standardized measures of alcohol and substance use, Alcohol Timeline Followback (TLFB) and the Brief Addiction Monitor (BAM) questionnaire. |
| Percentage of Days Abstinent | 6 months | Abstinence defined as no drinks consumed. |
| Percentage of Days of Heavy Drinking | 6 months | Heavy drinking is defined as consuming (in a 24 hour period) 3 or more drinks for women, or 4 or more drinks for men. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Active dTMS Participants will receive 30 dTMS treatments, administered 3 times per day over 10 consecutive business days, Each treatment visit will last approximately 30 minutes in total. | 6 |
| Total | 6 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Unable to complete preassessment MRI | 1 |
| Overall Study | Withdrawal by Subject | 3 |
Baseline characteristics
| Characteristic | Active dTMS |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 6 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 4 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 2 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 3 Participants |
| Race (NIH/OMB) White | 3 Participants |
| Region of Enrollment United States | 6 Participants |
| Sex: Female, Male Female | 2 Participants |
| Sex: Female, Male Male | 4 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 8 |
| other Total, other adverse events | 0 / 8 |
| serious Total, serious adverse events | 0 / 8 |
Outcome results
Primary
Number of Participants With Relapse to Alcohol 6 Months After Treatment
Six months after completing the intervention, participants will be contacted to determine self-reported relapse status. To determine relapse status, participants complete brief standardized measures of alcohol and substance use, Alcohol Timeline Followback (TLFB) and the Brief Addiction Monitor (BAM) questionnaire.
Time frame: 6 months
Population: Participants who completed at least half of the treatment sessions.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Active dTMS | Number of Participants With Relapse to Alcohol 6 Months After Treatment | 3 Participants |
Primary
Percentage of Days Abstinent
Abstinence defined as no drinks consumed.
Time frame: 6 months
Population: Participants who completed at least half of the treatment sessions.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Active dTMS | Percentage of Days Abstinent | 85.1 percentage of days | Standard Deviation 32.06 |
Primary
Percentage of Days of Heavy Drinking
Heavy drinking is defined as consuming (in a 24 hour period) 3 or more drinks for women, or 4 or more drinks for men.
Time frame: 6 months
Population: Participants who completed at least half of the treatment sessions.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Active dTMS | Percentage of Days of Heavy Drinking | 2.7 percentage of days | Standard Deviation 5.37 |