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Recruitment difficulties due to Covid-19 pandemic
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The purpose of this study is to evaluate the efficacy of intermittent theta burst repetitive transcranial magnetic stimulation (iTBS) as a treatment for Veterans with an alcohol use disorder (AUD) to decrease the exceedingly high rate of relapse associated with this condition. iTBS has demonstrated equivalent efficacy and safety to repetitive transcranial magnetic stimulation employing 10Hz stimulation protocols in treatment of depressive disorders. The advantage of iTBS is that it can be delivered in approximately 5 minutes where conventional 10Hz repetitive transcranial magnetic stimulation (rTMS) protocols are typically 20-25 minutes. It is hypothesized that Veterans with AUD who receive active iTBS applied to the left dorsolateral prefrontal cortex (DLPFC), compared to controls (i.e., Veterans with AUD who receive sham iTBS), will show significant decreases alcohol craving, depressive symptomatology and cigarette consumptions, as well as improved neurocognition, a longer period of abstinence, and a lower overall rate of relapse over 6 months following standard psychosocial treatment for AUD at VA substance treatment clinics. In exploratory analyses, it is also predicted that magnetic resonance measures of left DLPFC glutamate concentration, volume of anterior frontal cortical brain regions, and performance on fMRI tasks interrogating the function of the salience/reward circuits will serve as biomarkers of iTBS treatment response. The goal of this proposal is to implement treatment that effectively promotes sustained abstinence in Veterans with AUD, given long-term abstinence is related to optimal neurobiological, neuropsychological and psychosocial recovery and functioning.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Active iTBS | Active Comparator | Participants will be randomized to active or sham iTBS. |
|
| Sham iTBS | Sham Comparator | Participants will be randomized to active or sham iTBS. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Intermittent theta burst transcranial magnetic stimulation | Device | 20 iTBS sessions (active or sham) administered over the course of 2 weeks |
|
| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants Who Were Abstinent Through Month 6 | Number of particiants in active vs. sham who maintained completed abstinence from alcohol/substance over 6 months post final rTMS session. | 6 months |
| Measure | Description | Time Frame |
|---|---|---|
| Left Dorsolateral Prefrontal Region Glutamate/Creatine Ratio | Left dorsolateral prefrontal region glutamate/creatine ratio pre and post active/sham iTBS. Data were recorded in international units (IU) and converted to Z scores based on the entire sample (unit normal distribution, mean of 0, standard deviation of 1). Higher Z scores (standard deviation above the mean) indicate a greater metabolite concentration ratio and better functioning. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Timothy C Durazzo, PhD | Stanford University | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Palo Alto VA Health Care System | Palo Alto | California | 94304 | United States | ||
| Stanford University |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 37897693 | Derived | Durazzo TC, Humphreys K, LaRocca MA. Leadership Styles Experienced During Military Service Predict Later Anhedonic Depressive Symptoms and Self-Efficacy in Veterans With Alcohol Use Disorder. Mil Med. 2024 May 18;189(5-6):e1064-e1071. doi: 10.1093/milmed/usad405. | |
| 37146499 | Derived | Durazzo TC, McNerney MW, Hansen AM, Gu M, Sacchet MD, Padula CB. BDNF rs6265 Met carriers with alcohol use disorder show greater age-related decline of N-acetylaspartate in left dorsolateral prefrontal cortex. Drug Alcohol Depend. 2023 Jul 1;248:109901. doi: 10.1016/j.drugalcdep.2023.109901. Epub 2023 Apr 28. |
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From 20MAR20-31AUG21 no participants were recruited due the mandatory hiatus of recruitment of human participants (forced by the COVID-19 pandemic) and the Principal Investigator's mobilization to active military service. The PI discussed the recruitment issues with the Stanford NeuroChoice Initiative funding agency, and it was decided to discontinue recruitment in JUL21.
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| ID | Title | Description |
|---|---|---|
| FG000 | Active iTBS | Intermittent theta burst transcranial magnetic stimulation: Participants will be randomized to active or sham iTBS conditions, and receive 20 iTBS sessions over the course of 2 weeks |
| FG001 | Sham iTBS | Intermittent theta burst transcranial magnetic stimulation: Participants will be randomized to active or sham iTBS conditions, and receive 20 iTBS sessions over the course of 2 weeks |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Active iTBS | Intermittent theta burst transcranial magnetic stimulation: Participants will be randomized to active or sham iTBS conditions, and receive 20 iTBS sessions over the course of 2 weeks |
| BG001 | Sham iTBS |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Number of Participants Who Were Abstinent Through Month 6 | Number of particiants in active vs. sham who maintained completed abstinence from alcohol/substance over 6 months post final rTMS session. | Posted | Count of Participants | Participants | 6 months |
|
Baseline through 6 months after conclusion of treatment
Participants were systematically screened for any biomedical, psychiatric or other physical condition that was associated with serious adverse events or adverse events.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Active iTBS | Intermittent theta burst transcranial magnetic stimulation: Participants will be randomized to active or sham iTBS conditions, and receive 20 iTBS sessions over the course of 2 weeks |
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The study was terminated early before enrolling the planned number of participants, therefore the data analysis is underpowered.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Timothy C. Durazzo/Project PI | Stanford University School of Medicine, Department of Psychiatry and Behavioral Sciences | 650-493-5000 | 62982 | tdurazzo@stanford.edu |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Aug 1, 2017 | Feb 15, 2023 | Prot_SAP_000.pdf |
| ICF | No | No | Yes | Informed Consent Form | Nov 29, 2021 | Feb 15, 2023 | ICF_001.pdf |
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| ID | Term |
|---|---|
| D000437 | Alcoholism |
| D003866 | Depressive Disorder |
| D000073865 | Cigarette Smoking |
| ID | Term |
|---|---|
| D019973 | Alcohol-Related Disorders |
| D019966 | Substance-Related Disorders |
| D064419 | Chemically-Induced Disorders |
| D001523 | Mental Disorders |
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| baseline and follow-up (approximately 2 weeks) |
| Left Dorsolateral Prefrontal Cortex Thickness | Left dorsolateral prefrontal cortex thickness pre and post active/sham iTBS; hypothesized that increased thickness corresponds to improved cytoarchitectural integrity of the left dorsolateral prefrontal cortex. | baseline and follow-up (approximately 2 weeks) |
| General Depressive Symptoms | Beck Depression Inventory-II score pre and post active/sham iTBS (score range, 0 to 63, higher scores indicate more severe symptoms). | baseline and follow-up (approximately 2 weeks) |
| Anhedonic Depressive Symptoms | Anhedonic depressive symptoms from Mood and Anxiety Symptom Questionnaire (MASQ, 30-item version; score range: 10 to 50, high scores correspond to more severe symptoms). | baseline and follow-up (approximately 2 weeks) |
| Stanford |
| California |
| 94305 |
| United States |
| Residential treatment team requested participant withdraw due to multiple conflicting appointments. |
|
Intermittent theta burst transcranial magnetic stimulation: Participants will be randomized to active or sham iTBS conditions, and receive 20 iTBS sessions over the course of 2 weeks
| BG002 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Count of Participants | Participants |
|
| Education | Mean | Standard Deviation | years |
|
|
|
|
| Secondary | Left Dorsolateral Prefrontal Region Glutamate/Creatine Ratio | Left dorsolateral prefrontal region glutamate/creatine ratio pre and post active/sham iTBS. Data were recorded in international units (IU) and converted to Z scores based on the entire sample (unit normal distribution, mean of 0, standard deviation of 1). Higher Z scores (standard deviation above the mean) indicate a greater metabolite concentration ratio and better functioning. | Participants with available data are included in the analysis. | Posted | Mean | Standard Error | z-score | baseline and follow-up (approximately 2 weeks) |
|
|
|
|
| Secondary | Left Dorsolateral Prefrontal Cortex Thickness | Left dorsolateral prefrontal cortex thickness pre and post active/sham iTBS; hypothesized that increased thickness corresponds to improved cytoarchitectural integrity of the left dorsolateral prefrontal cortex. | Participants with data available at each respective assessment point. | Posted | Mean | Standard Deviation | mm | baseline and follow-up (approximately 2 weeks) |
|
|
|
|
| Secondary | General Depressive Symptoms | Beck Depression Inventory-II score pre and post active/sham iTBS (score range, 0 to 63, higher scores indicate more severe symptoms). | Participants with available data are included in the analysis. | Posted | Mean | Standard Error | score on a scale | baseline and follow-up (approximately 2 weeks) |
|
|
|
|
| Secondary | Anhedonic Depressive Symptoms | Anhedonic depressive symptoms from Mood and Anxiety Symptom Questionnaire (MASQ, 30-item version; score range: 10 to 50, high scores correspond to more severe symptoms). | Participants with available data are included in the analysis. | Posted | Mean | Standard Error | score on a scale | baseline and follow-up (approximately 2 weeks) |
|
|
|
|
| 0 |
| 8 |
| 0 |
| 8 |
| 0 |
| 8 |
| EG001 | Sham iTBS | Intermittent theta burst transcranial magnetic stimulation: Participants will be randomized to active or sham iTBS conditions, and receive 20 iTBS sessions over the course of 2 weeks | 0 | 9 | 0 | 9 | 0 | 9 |
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| D019964 | Mood Disorders |
| D000073869 | Tobacco Smoking |
| D012907 | Smoking |
| D001519 | Behavior |
| D064424 | Tobacco Use |
| Follow-up |
|
|