Examining the Effectiveness of Deep TMS in Veterans With Alcohol Use Disorder
Primary Purpose
Alcohol Use Disorder (AUD), Transcranial Magnetic Stimulation
Status
Active
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
Deep Transcranial Magnetic Stimulation (dTMS) H7 coil
Sponsored by
About this trial
This is an interventional treatment trial for Alcohol Use Disorder (AUD) focused on measuring Veterans, Deep Transcranial Magnetic Stimulation (dTMS), Alcohol Use Disorder, Neuroimaging, Relapse
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.
Sites / Locations
- VA Palo Alto Health Care System
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Active dTMS
Arm Description
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.
Outcomes
Primary Outcome Measures
Relapse to alcohol 6months after treatment
Six months after completing the intervention, participants will be contacted to determine self-reported relapse status. Participants will complete brief standardized measures of alcohol and substance use, Alcohol Timeline Followback (TLFB) and the Brief Addiction Monitor (BAM) questionnaire.
Secondary Outcome Measures
Full Information
NCT ID
NCT04927364
First Posted
June 1, 2021
Last Updated
July 2, 2023
Sponsor
Stanford University
Collaborators
VA Palo Alto Health Care System
1. Study Identification
Unique Protocol Identification Number
NCT04927364
Brief Title
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
2. Study Status
Record Verification Date
July 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
September 6, 2022 (Actual)
Primary Completion Date
May 17, 2023 (Actual)
Study Completion Date
November 2023 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Stanford University
Collaborators
VA Palo Alto Health Care System
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Alcohol Use Disorder (AUD), Transcranial Magnetic Stimulation
Keywords
Veterans, Deep Transcranial Magnetic Stimulation (dTMS), Alcohol Use Disorder, Neuroimaging, Relapse
7. Study Design
Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
10 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Active dTMS
Arm Type
Experimental
Arm Description
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.
Intervention Type
Device
Intervention Name(s)
Deep Transcranial Magnetic Stimulation (dTMS) H7 coil
Intervention Description
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.
Primary Outcome Measure Information:
Title
Relapse to alcohol 6months after treatment
Description
Six months after completing the intervention, participants will be contacted to determine self-reported relapse status. Participants will complete brief standardized measures of alcohol and substance use, Alcohol Timeline Followback (TLFB) and the Brief Addiction Monitor (BAM) questionnaire.
Time Frame
6 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
21 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Claudia Padula, PhD
Organizational Affiliation
Stanford University
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Michelle Madore, PhD
Organizational Affiliation
Stanford University
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Timothy Durazzo, PhD
Organizational Affiliation
Stanford University
Official's Role
Principal Investigator
Facility Information:
Facility Name
VA Palo Alto Health Care System
City
Palo Alto
State/Province
California
ZIP/Postal Code
94304
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing Plan Description
Any data, specimens, forms, reports, and other records that leave the site will be identified only by a participant ID number to maintain confidentiality. The ID Number will have no relationship to any aspect of identifiable private information. Therefore, the data associated with each participant will be completely de-identified and there will be no mechanism by which users can re-identify participant data (e.g., name, address) with the subject code.
IPD Sharing Time Frame
Three to twelve months after publication.
IPD Sharing Access Criteria
Researchers who provide a methodologically sound proposal.
Citations:
PubMed Identifier
19710631
Citation
Koob GF, Volkow ND. Neurocircuitry of addiction. Neuropsychopharmacology. 2010 Jan;35(1):217-38. doi: 10.1038/npp.2009.110. Erratum In: Neuropsychopharmacology. 2010 Mar;35(4):1051.
Results Reference
background
PubMed Identifier
28082874
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.
Results Reference
background
PubMed Identifier
35067356
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.
Results Reference
background
Learn more about this trial
Examining the Effectiveness of Deep TMS in Veterans With Alcohol Use Disorder
We'll reach out to this number within 24 hrs