Stimulant Use Disorder, Substance-related Disorders
Conditions
Keywords
Magnetic resonance imaging, Transcranial magnetic stimulation, Dopamine, Reward processing
Brief summary
The purpose of this study is to establish a new treatment (repetitive transcranial stimulation (rTMS)) for Veterans with stimulant use disorder (SUD). Despite the large public health burden imposed by SUD, there is currently no FDA-approved or widely recognized effective somatic treatment. rTMS may be a promising treatment option for SUD. In this study, we will demonstrate the feasibility of applying rTMS to Veterans with SUD, examine the efficacy of rTMS in the treatment of SUD, and explore biomarkers that may guide patient selection for rTMS treatment and predict treatment response.
Interventions
DEVICERepetitive transcranial magnetic stimulation (rTMS)
rTMS is a non-invasive procedure in which administering a transient magnetic field induces electrical currents in specific, targeted brain regions. The intervention (active and sham) will be administered in 8 sessions across 2 weeks. The brain region targeted is the dorsolateral prefrontal cortex.
Sponsors
Stanford University
VA Office of Research and Development
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Intervention model description
Participants will be randomly assigned to one of two groups to receive active or sham rTMS.
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Structured Clinical Interview for DSM Disorders (SCID) confirmed diagnosis of SUD, severe * Last use of stimulants \>1 and \<6 weeks * Stable medication regimen (no change in dose or agents between 2 weeks prior to the start of and throughout the treatment phase of the study) * Stable social environment and housing to enable regular attendance at clinic visits. * Ability to undergo cognitive testing, functional magnetic resonance imaging (fMRI) scans, and rTMS (no contraindications) * Intelligence Quotient (IQ) \> 80 * Stable medical health * Veteran at Palo Alto VA's Addiction Treatment Services
Exclusion criteria
* Pregnant or lactating female * History of prior adverse reaction to TMS * On medications thought to significantly lower seizure threshold, e.g.: * clozapine * chlorpromazine * clomipramine * bupropion \> 400 mg/day * Use of direct dopaminergic antagonists or agonists * History of seizures or conditions known to substantially increase risk for seizures * Implants or medical devices incompatible with TMS * Acute or unstable chronic medical illness that would affect participation or compliance with study procedures, e.g. unstable angina * Unstable psychiatric symptoms that precludes consistent participation in the study, e.g.: * active current suicidal intent or plan * severe psychosis * Inability to undergo fMRI scan, e.g. claustrophobia, presence of ferromagnetic objects in subject's body * Other substance use disorder not in sustained remission * Chronic or recurring Axis I psychiatric condition preceding SUD other than PTSD
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Relapsed | 3 months after last rTMS treatment | Rate of stimulant use relapse compared between active vs. sham rTMS groups |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Reward Circuit Function and Signaling | Within 1 week before and after rTMS treatment | Before and after treatment, participants underwent functional magnetic resonance imaging (fMRI) imaging while completing the Monetary Incentive Delay Task, a validated probe of reward processing circuit function and dysfunction. Signaling in the substantia nigra measured in an individual-subject, native space region of interest approach as a marker of dopaminergic reward processing function, as well as in voxel-wise, whole-brain exploratory analyses. Changes in reward function and signaling compared between active vs. sham rTMS groups |
Countries
United States
Participant flow
Pre-assignment details
8 people did not enter intervention phase. Defining drop out as those who started the intervention and dropped out before completing intervention & outcome measures.
Participants by arm
| Arm | Count |
|---|---|
| Active rTMS Receive active rTMS
Repetitive transcranial magnetic stimulation (rTMS): rTMS is a non-invasive procedure which administers a transient magnetic field inducing electrical currents in specific, targeted brain regions. The intervention was administered in 8 sessions across 2 weeks. The brain region targeted is the dorsolateral prefrontal cortex. | 7 |
| Sham rTMS All subjects underwent the same procedure as the active rTMS group except that the inactive side of the coil was placed on the subject's scalp. The experience receiving sham rTMS was identical except that no electrical current was administered. | 11 |
| Total | 18 |
Baseline characteristics
| Characteristic | Sham rTMS | Total | Active rTMS |
|---|---|---|---|
| Age, Continuous | 45.0 Year STANDARD_DEVIATION 16.9 | 43.2 Year STANDARD_DEVIATION 15 | 40.4 Year STANDARD_DEVIATION 11.3 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants | 3 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 9 Participants | 15 Participants | 6 Participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 11 Participants | 18 Participants | 7 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 7 | 0 / 11 |
| other Total, other adverse events | 0 / 7 | 0 / 11 |
| serious Total, serious adverse events | 0 / 7 | 0 / 11 |
Outcome results
Primary
Number of Participants Relapsed
Rate of stimulant use relapse compared between active vs. sham rTMS groups
Time frame: 3 months after last rTMS treatment
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Active rTMS | Number of Participants Relapsed | 4 Participants |
| Sham TMS | Number of Participants Relapsed | 8 Participants |
Secondary
Reward Circuit Function and Signaling
Before and after treatment, participants underwent functional magnetic resonance imaging (fMRI) imaging while completing the Monetary Incentive Delay Task, a validated probe of reward processing circuit function and dysfunction. Signaling in the substantia nigra measured in an individual-subject, native space region of interest approach as a marker of dopaminergic reward processing function, as well as in voxel-wise, whole-brain exploratory analyses. Changes in reward function and signaling compared between active vs. sham rTMS groups
Time frame: Within 1 week before and after rTMS treatment
Population: Unable to conduct this portion of study due to COVID-19 pandemic related logistical challenges. Data will never be collected in the future.