Clinical trial NCT04927364: Examining the Effectiveness of Deep TMS in Veterans With Alcohol Use Disorder
Official title: Examining the Effectiveness of Deep TMS in Veterans With Alcohol Use Disorder
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: NA
Conditions: Alcohol Use Disorder (AUD)
Transcranial Magnetic Stimulation
Keywords: Veterans
Deep Transcranial Magnetic Stimulation (dTMS)
Alcohol Use Disorder
Neuroimaging
Relapse
Lead sponsor: Stanford University
Sponsor class: OTHER
Collaborators: name: VA Palo Alto Health Care System
First posted: 2021-06-16
Enrollment: 8
Sex: ALL
Minimum age (years): 21
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Number of Participants With Relapse to Alcohol 6 Months After Treatment
timeFrame: 6 months
measure: Percentage of Days Abstinent
timeFrame: 6 months
measure: Percentage of Days of Heavy Drinking
timeFrame: 6 months
Secondary outcomes:
Other outcomes:
Locations:
city: Palo Alto
country: United States
facility: VA Palo Alto Health Care System
state: California
Study officials:
affiliation: Stanford University
name: Claudia Padula, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Stanford University
name: Michelle Madore, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Stanford University
name: Timothy Durazzo, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Koob GF, Volkow ND. Neurocircuitry of addiction. Neuropsychopharmacology. 2010 Jan;35(1):217-38. doi: 10.1038/npp.2009.110.
citation: Peters SK, Dunlop K, Downar J. Cortico-Striatal-Thalamic Loop Circuits of the Salience Network: A Central Pathway in Psychiatric Disease and Treatment. Front Syst Neurosci. 2016 Dec 27;10:104. doi: 10.3389/fnsys.2016.00104. eCollection 2016.
citation: Harel M, Perini I, Kampe R, Alyagon U, Shalev H, Besser I, Sommer WH, Heilig M, Zangen A. Repetitive Transcranial Magnetic Stimulation in Alcohol Dependence: A Randomized, Double-Blind, Sham-Controlled Proof-of-Concept Trial Targeting the Medial Prefrontal and Anterior Cingulate Cortices. Biol Psychiatry. 2022 Jun 15;91(12):1061-1069. doi: 10.1016/j.biopsych.2021.11.020. Epub 2021 Dec 6.