An interventional study of Intermittent theta burst transcranial magnetic stimulation in Alcohol Use Disorder, Depressive Disorder and Cigarette Smoking, sponsored by Stanford University. Terminated at 2 sites in United States. Open to participants aged 21 Years to 65 Years. Per ClinicalTrials.gov, last updated 2023-10-16.
Sponsored by Stanford University · Not applicable, Interventional, and Treatment
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.
Exclusion Criteria:
Participants will be randomized to active or sham iTBS.
Device: Intermittent theta burst transcranial magnetic stimulation
Participants will be randomized to active or sham iTBS.
Device: Intermittent theta burst transcranial magnetic stimulation
20 iTBS sessions (active or sham) administered over the course of 2 weeks
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.
Time frame: 6 months
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.
Time frame: 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.
Time frame: 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).
Time frame: 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).
Time frame: baseline and follow-up (approximately 2 weeks)
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.
| Milestone | Active iTBS | Sham iTBS |
|---|---|---|
| Started | 8 | 9 |
| Completed | 5 | 7 |
| Not completed | 3 | 2 |
| Withdrew: Protocol violation | 2 | 1 |
| Withdrew: Participant self-discharged against medical advice from treatment program during active study phase | 1 | 0 |
| Withdrew: Residential treatment team requested participant withdraw due to multiple conflicting appointments. | 0 | 1 |
Number of particiants in active vs. sham who maintained completed abstinence from alcohol/substance over 6 months post final rTMS session.
| Participants | Active iTBS | Sham iTBS |
|---|---|---|
| Number of Participants Who Were Abstinent Through Month 6 | 5 | 7 |
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.
| z-score | Active iTBS | Sham iTBS |
|---|---|---|
| baseline | 0.31 ± 0.29 | 0.02 ± 0.30 |
| week 2 | 0.25 ± 0.29 | 0.29 ± 0.22 |
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.
| mm | Active iTBS | Sham iTBS |
|---|---|---|
| Baseline | 2.34 ± 0.14 | 2.36 ± 0.15 |
| Follow-up | 2.39 ± 0.17 | 2.37 ± 0.19 |
Beck Depression Inventory-II score pre and post active/sham iTBS (score range, 0 to 63, higher scores indicate more severe symptoms).
| score on a scale | Active iTBS | Sham iTBS |
|---|---|---|
| Baseline | 18.4 ± 3.4 | 18.0 ± 3.1 |
| Follow-up | 10.0 ± 4.0 | 11.9 ± 2.9 |
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).
| score on a scale | Active iTBS | Sham iTBS |
|---|---|---|
| baseline | 29.1 ± 2.8 | 32.7 ± 2.6 |
| Follow-up | 22.5 ± 3.3 | 30.5 ± 2.4 |
Collected over Baseline through 6 months after conclusion of treatment. Non-serious events are listed at a 0% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Active iTBS | 0/8 (0%) | 0/8 (0%) | 0/8 (0%) |
| Sham iTBS | 0/9 (0%) | 0/9 (0%) | 0/9 (0%) |
| Age, Continuous(years) | Active iTBS | Sham iTBS | Total |
|---|---|---|---|
| Mean | 32.0 ± 9.8 | 48.5 ± 12.4 | 42.3 ± 11.1 |
| Sex: Female, Male(Participants) | Active iTBS | Sham iTBS | Total |
|---|---|---|---|
| Female | 0 | 1 | 1 |
| Male | 8 | 8 | 16 |
| Ethnicity (NIH/OMB)(Participants) | Active iTBS | Sham iTBS | Total |
|---|---|---|---|
| Hispanic or Latino | 2 | 2 | 4 |
| Not Hispanic or Latino | 6 | 7 | 13 |
| Unknown or Not Reported | 0 | 0 | 0 |
| Race (NIH/OMB)(Participants) | Active iTBS | Sham iTBS | Total |
|---|---|---|---|
| American Indian or Alaska Native | 2 | 1 | 3 |
| Asian | 0 | 0 | 0 |
| Native Hawaiian or Other Pacific Islander | 0 | 0 | 0 |
| Black or African American | 1 | 2 | 3 |
| White | 5 | 6 | 11 |
| More than one race | 0 | 0 | 0 |
| Unknown or Not Reported | 0 | 0 | 0 |
| Region of Enrollment(Participants) | Active iTBS | Sham iTBS | Total |
|---|---|---|---|
| United States | 8 | 9 | 17 |
| Education(years) | Active iTBS | Sham iTBS | Total |
|---|---|---|---|
| Mean | 13.5 ± 1.5 | 13.3 ± 1.8 | 13.4 ± 1.7 |
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