Trial Outcomes & Findings for Transcranial Magnetic Stimulation for the Treatment of Veterans With Alcohol Use Disorders (NCT NCT03191266)

NCT ID: NCT03191266

Last Updated: 2026-01-28

Results Overview

For the 6 months following completion of active or sham rTMS treatment, participants were contacted monthly, via telephone or in person, to complete a brief standardized measure of alcohol and substance use, and psychiatric symptoms to assess for changes in these variables over the previous 30 days.

Recruitment status

COMPLETED

Study phase

NA

Target enrollment

49 participants

Primary outcome timeframe

6 months following last TMS session

Results posted on

2026-01-28

Participant Flow

Eighty-eight Veterans with alcohol use disorder, from a residential treatment program at the VA Palo Alto Health Care System, completed an in-person screen for study eligibility.Thirty-four individuals were not eligible for participation; the most common reasons for exclusion were a history of bipolar or schizophrenia spectrum disorders or moderate or greater severity traumatic brain injury. Five other participants were eligible, but declined to complete the 2-week study procedure.

Eighty-eight Veterans with alcohol use disorder, completed an in-person screen for study eligibility. Thirty-four individuals were not eligible for participation. Five other participants were eligible, but three declined, not wishing to complete neuroimaging procedures, and two did not wish to complete the approximately 2-week iTBS procedure. The final participant group consisted of 49 individuals.

Participant milestones

Participant milestones
Measure
Active rTMS
Active rTMS will receive an intermittent rTMS stimulation protocol.
Sham rTMS
Sham rTMS will receive all conditions except the actual intermittent theta burst rTMS stimulation.
Overall Study
STARTED
25
24
Overall Study
COMPLETED
22
22
Overall Study
NOT COMPLETED
3
2

Reasons for withdrawal

Reasons for withdrawal
Measure
Active rTMS
Active rTMS will receive an intermittent rTMS stimulation protocol.
Sham rTMS
Sham rTMS will receive all conditions except the actual intermittent theta burst rTMS stimulation.
Overall Study
Space occupying lesion on MRI; PI removed participant after randomization, but before TMS initiation
0
1
Overall Study
Withdrawal by Subject
3
1

Baseline Characteristics

Transcranial Magnetic Stimulation for the Treatment of Veterans With Alcohol Use Disorders

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure
Active rTMS
n=25 Participants
Active rTMS will receive an intermittent rTMS stimulation protocol.
Sham rTMS
n=24 Participants
Sham rTMS will receive all conditions except the actual intermittent theta burst rTMS stimulation.
Total
n=49 Participants
Total of all reporting groups
Ethnicity (NIH/OMB)
Hispanic or Latino
6 Participants
n=158 Participants
5 Participants
n=157 Participants
11 Participants
n=315 Participants
Ethnicity (NIH/OMB)
Not Hispanic or Latino
19 Participants
n=158 Participants
19 Participants
n=157 Participants
38 Participants
n=315 Participants
Age, Continuous
50.6 years
STANDARD_DEVIATION 13.8 • n=158 Participants
51.3 years
STANDARD_DEVIATION 13.8 • n=157 Participants
51.0 years
STANDARD_DEVIATION 13.7 • n=315 Participants
Sex: Female, Male
Female
0 Participants
n=158 Participants
1 Participants
n=157 Participants
1 Participants
n=315 Participants
Sex: Female, Male
Male
25 Participants
n=158 Participants
23 Participants
n=157 Participants
48 Participants
n=315 Participants
Ethnicity (NIH/OMB)
Unknown or Not Reported
0 Participants
n=158 Participants
0 Participants
n=157 Participants
0 Participants
n=315 Participants
Race (NIH/OMB)
American Indian or Alaska Native
3 Participants
n=158 Participants
0 Participants
n=157 Participants
3 Participants
n=315 Participants
Race (NIH/OMB)
Asian
1 Participants
n=158 Participants
1 Participants
n=157 Participants
2 Participants
n=315 Participants
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
0 Participants
n=158 Participants
1 Participants
n=157 Participants
1 Participants
n=315 Participants
Race (NIH/OMB)
Black or African American
3 Participants
n=158 Participants
5 Participants
n=157 Participants
8 Participants
n=315 Participants
Race (NIH/OMB)
White
18 Participants
n=158 Participants
17 Participants
n=157 Participants
35 Participants
n=315 Participants
Race (NIH/OMB)
More than one race
0 Participants
n=158 Participants
0 Participants
n=157 Participants
0 Participants
n=315 Participants
Race (NIH/OMB)
Unknown or Not Reported
0 Participants
n=158 Participants
0 Participants
n=157 Participants
0 Participants
n=315 Participants
Formal education
14.3 years
STANDARD_DEVIATION 2.4 • n=158 Participants
14.0 years
STANDARD_DEVIATION 1.6 • n=157 Participants
14.2 years
STANDARD_DEVIATION 2.0 • n=315 Participants

PRIMARY outcome

Timeframe: 6 months following last TMS session

For the 6 months following completion of active or sham rTMS treatment, participants were contacted monthly, via telephone or in person, to complete a brief standardized measure of alcohol and substance use, and psychiatric symptoms to assess for changes in these variables over the previous 30 days.

Outcome measures

Outcome measures
Measure
Active rTMS
n=22 Participants
Active rTMS will receive an intermittent rTMS stimulation protocol.
Sham rTMS
n=22 Participants
Sham rTMS will receive all conditions except the actual intermittent theta burst rTMS stimulation.
Number of Participants Who Abstained From Alcohol
13 Participants
9 Participants

SECONDARY outcome

Timeframe: Baseline

Population: This grouping within the active rTMS arm (Abstinent or Resumed alcohol consumption during the 6 month follow-up period) was conducted to determine if baseline glutamate level can serve as a biomarker to differential those participants, in the active rTMS group who main continuous abstinence versus those who resumed alcohol consumption. The investigators did not hypothesize that baseline glutamate would predict outcome (abstinent vs. resumed) in the sham rTMS group.

Determine if baseline glutamate level can serve as a biomarker to differential those participant, in the active rTMS group who main continuous abstinence versus those who resumed alcohol consumption.

Outcome measures

Outcome measures
Measure
Active rTMS
n=8 Participants
Active rTMS will receive an intermittent rTMS stimulation protocol.
Sham rTMS
n=6 Participants
Sham rTMS will receive all conditions except the actual intermittent theta burst rTMS stimulation.
Glutamate Concentration in the Left Dorsolateral Prefrontal Cortex (as Measured With Single Voxel Spectroscopy)
26.2 mmol/L
Standard Deviation 2.6
19.7 mmol/L
Standard Deviation 3.0

SECONDARY outcome

Timeframe: Baseline

Population: This grouping within the active rTMS arm (Abstinent or Resumed alcohol consumption during the 6 month follow-up period) was conducted to determine if baseline left caudal and rostral middle frontal and left superior frontal gyri could gyrus serve as a biomarker to differential those participants, in the active rTMS group, who main continuous abstinence versus those who resumed consumption. We did not hypothesize baseline volumes would predict outcome (abstinent vs. resumed) in the sham group.

Determine if volume in anterior frontal cortical regions can serve as biomarkers to predict rTMS treatment response in Veterans with AUD who receive active TMS. Specific regions of interest were the left caudal and rostral middle frontal gyrus and left superior frontal gyrus because these regions correspond to the rTMS anatomical target.

Outcome measures

Outcome measures
Measure
Active rTMS
n=9 Participants
Active rTMS will receive an intermittent rTMS stimulation protocol.
Sham rTMS
n=8 Participants
Sham rTMS will receive all conditions except the actual intermittent theta burst rTMS stimulation.
Volume in Anterior Frontal Cortical Regions (as Measured With FreeSurfer)
left superior frontal gyrus
23503 Volume in cubic millimeters
Standard Deviation 2693
21086 Volume in cubic millimeters
Standard Deviation 2729
Volume in Anterior Frontal Cortical Regions (as Measured With FreeSurfer)
left caudal middle frontal gyrus
6587 Volume in cubic millimeters
Standard Deviation 1029
6236 Volume in cubic millimeters
Standard Deviation 933
Volume in Anterior Frontal Cortical Regions (as Measured With FreeSurfer)
left rostral middle gyrus frontal gyrus
14778 Volume in cubic millimeters
Standard Deviation 1963
14071 Volume in cubic millimeters
Standard Deviation 2549

SECONDARY outcome

Timeframe: Baseline

Population: Analysis was conducted to determine if BDNF polymorphisms (rs6265) can serve as biomarkers to predict rTMS treatment response in Veterans with AUD. Analysis focused on comparing Val homozygote frequency, in active rTMS arm participants, who maintained continuous abstinence (Abstinent) versus those who resumed alcohol consumption (Resumed) over the 6-month follow-up period. We did not have specific hypotheses about BDNF polymorphism rs6265 for abstinence or resumption of alcohol in sham arm.

Determine if BDNF polymorphisms (rs6265) can serve as biomarkers to predict rTMS treatment response in Veterans with AUD. Analysis focused on comparing Val homozygote frequency, in active rTMS arm participants, who maintained continuous abstinence (Abstinent) versus those who resumed alcohol consumption (Resumed) over the 6-month follow-up period. There were a limited number of participants who completed the genotyping procedure; therefore, results are likely not generalizable.

Outcome measures

Outcome measures
Measure
Active rTMS
n=7 Participants
Active rTMS will receive an intermittent rTMS stimulation protocol.
Sham rTMS
n=4 Participants
Sham rTMS will receive all conditions except the actual intermittent theta burst rTMS stimulation.
BDNF Polymorphisms (as Measured With TaqMan Genotyping Assays or Similar Assays)
5 Participants
4 Participants

Adverse Events

Active rTMS

Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths

Sham rTMS

Serious events: 1 serious events
Other events: 0 other events
Deaths: 1 deaths

Serious adverse events

Serious adverse events
Measure
Active rTMS
n=22 participants at risk
Active rTMS will receive an intermittent rTMS stimulation protocol.
Sham rTMS
n=22 participants at risk
Sham rTMS will receive all conditions except the actual intermittent theta burst rTMS stimulation.
Psychiatric disorders
suicide
0.00%
0/22 • 1 year post study completion for each participant.
Participant was the under the care of VA clinicians at the time of death and was formally screened for suicidal ideation/intent by different VA clinicians on 9 and 3 days prior to death and denied any suicidal ideation.
4.5%
1/22 • Number of events 1 • 1 year post study completion for each participant.
Participant was the under the care of VA clinicians at the time of death and was formally screened for suicidal ideation/intent by different VA clinicians on 9 and 3 days prior to death and denied any suicidal ideation.

Other adverse events

Adverse event data not reported

Additional Information

Dr. Timothy C. Durazzo

VA Palo Alto Health Care System

Phone: 650-493-5000

Results disclosure agreements

  • Principal investigator is a sponsor employee
  • Publication restrictions are in place