Cocaine-Related Disorders
Conditions
Brief summary
The overarching goal of this project is to examine the effect of combining theta burst stimulation (TBS) and N-acetylcysteine (NAC) on cocaine craving and brain response to cocaine-related images.
Interventions
DRUGN-acetylcysteine
N-acetylcysteine (NAC) is a medication that is used to treat paracetamol (acetaminophen) overdose, and to loosen thick mucus in individuals with cystic fibrosis or chronic obstructive pulmonary disease. It has a long-established safety record in adults and children, with FDA approval since 1963. The side effects most commonly noted in people who take NAC by mouth include diarrhea, nausea, vomiting, and headache. These side effects are usually mild and go away even with continued use of NAC by mouth. There is also a risk of a skin reaction, such as flushing, itching, or rash. A meta-analysis of studies evaluating long-term oral treatment with NAC for prevention of chronic bronchitis found that NAC was well tolerated, with generally mild, most commonly gastrointestinal adverse effects that did not require treatment interruption.
Theta-burst stimulation (TBS), a form of repetitive transcranial magnetic stimulation (rTMS), affects brain areas stimulated directly underneath the scalp and brain areas that are functionally connected.
Sponsors
National Institute on Drug Abuse (NIDA)
Medical University of South Carolina
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
Yes
Inclusion criteria
1\. Age 18-65 2. English fluency 4. Meet criteria for cocaine use disorder (CUD), as determined by DSM-V criteria, using the Structured Clinical Interview for DSM-V. 5\. Enrolled in an intensive outpatient treatment program (MUSC Center for Drug and Alcohol Programs Intensive Outpatient Program (CDAP-IOP) or currently engaged in treatment for substance related problems. 6\. Able to read and understand questionnaires and informed consent 7. Lives within 50 miles of the study site. 8. Is not at elevated risk of seizure (i.e., does not have a history of seizures, is not currently prescribed medications known to lower seizure threshold) 9. Does not have metal objects in the head/neck. 10. Does not have a history of traumatic brain injury, including a head injury that resulted in hospitalization, loss of consciousness for more than 10 minutes, or having ever been informed that they have an epidural, subdural, or subarachnoid hemorrhage. 11\. Does not have a history of claustrophobia leading to significant clinical anxiety symptoms.
Exclusion criteria
1. Past head injury or primary neurological disorder associated with MRI abnormalities, including dementia, MCI, brain tumors, epilepsy, Parkinson's disease, or demyelinating diseases 2. Any physical or intellectual disability affecting completion of assessments 3. Any contraindication to MRI 4. Current or past psychosis 5. ECT in last 6 months 6. Among females, pregnancy at screening will be exclusionary. Females of child bearing potential must agree to undergo a pregnancy test 72 hours prior to the fMRI scanning session and regularly before and during the medication trial. They must further agree to notify the study physician or PA if they become pregnant during the study. 7. Clinical Institute Withdrawal Assessment (CIWA-Ar) scale will be used to assess alcohol withdrawal. Individuals with CIWA \> 8 will be excluded. 8. Individuals with unstable medical illness (e.g., hypertension, diabetes, myocardial infarction) 9. Has current suicidal ideation or homicidal ideation. 10. Has the need for maintenance or acute treatment with any psychoactive medication including anti-seizure medications and medications for ADHD 11. Suffers from chronic migraines 12. Any physical or intellectual disability affecting completion of assessments
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Orbitofrontal Cortex (OFC) BOLD Signal During Cocaine Cue Reactivity Task (Pre- vs. Post-TBS) | From baseline to immediately post-TBS | Measured using fMRI during cocaine cue reactivity task. Percent BOLD signal change in OFC from baseline (Visit 2) to post-TBS (Visit 3). Measured using functional MRI during a cocaine cue reactivity task. The outcome reflects the change in raw BOLD signal in the orbitofrontal cortex (OFC) between baseline and post-TBS sessions. Signal change was calculated by comparing activation during cocaine-related image blocks versus neutral image blocks. Values are reported as raw BOLD signal units (not percentages). |
| Change in POMS Score From Baseline to Post-TBS | From baseline to immediately post-TBS | Total POMS score measured before and after TBS. Higher scores indicate worse mood. |
| Change in Cocaine Craving Rating From Baseline to Post-TBS | From baseline to immediately post-TBS | Self-reported craving measured using NRS (1-10) before and after TBS. Higher scores indicate greater craving. |
Countries
United States
Participant flow
Pre-assignment details
Only 32 were randomized and started treatment.
Participants by arm
| Arm | Count |
|---|---|
| Active Theta Burst Stimulation Two trains of 120-second active cTBS consisted of 3-pulse bursts delivered at 5 Hz. | 16 |
| Sham Theta Burst Stimulation Two trains of 120-second sham cTBS consisted of 3-pulse bursts delivered at 5 Hz. | 16 |
| Total | 32 |
Baseline characteristics
| Characteristic | Sham Theta Burst Stimulation | Total | Active Theta Burst Stimulation |
|---|---|---|---|
| Age, Continuous | 53.8 year STANDARD_DEVIATION 10.9 | 51.1 year STANDARD_DEVIATION 10.9 | 48.3 year STANDARD_DEVIATION 10.5 |
| Cocaine Craving Rating | 4.45 score on a scale STANDARD_DEVIATION 1.98 | 4.42 score on a scale STANDARD_DEVIATION 1.98 | 4.39 score on a scale STANDARD_DEVIATION 2.04 |
| OFC brain activity | -0.0012 Percent BOLD signal change STANDARD_DEVIATION 0.0102 | 0.0018 Percent BOLD signal change STANDARD_DEVIATION 0.0102 | 0.0049 Percent BOLD signal change STANDARD_DEVIATION 0.0096 |
| Profile of Mood States (POMS) | 18.75 POMS score STANDARD_DEVIATION 30.95 | 21.13 POMS score STANDARD_DEVIATION 32.52 | 23.50 POMS score STANDARD_DEVIATION 34.86 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 2 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 11 Participants | 19 Participants | 8 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 | 4 Participants | 11 Participants | 7 Participants |
| Sex: Female, Male Female | 2 Participants | 7 Participants | 5 Participants |
| Sex: Female, Male Male | 14 Participants | 25 Participants | 11 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 16 | 0 / 16 |
| other Total, other adverse events | 0 / 16 | 0 / 16 |
| serious Total, serious adverse events | 0 / 16 | 0 / 16 |
Outcome results
Primary
Change in Cocaine Craving Rating From Baseline to Post-TBS
Self-reported craving measured using NRS (1-10) before and after TBS. Higher scores indicate greater craving.
Time frame: From baseline to immediately post-TBS
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Active Theta Burst Stimulation | Change in Cocaine Craving Rating From Baseline to Post-TBS | 3.31 score on a scale | Standard Deviation 2.32 |
| Sham Theta Burst Stimulation | Change in Cocaine Craving Rating From Baseline to Post-TBS | 3.99 score on a scale | Standard Deviation 2.43 |
Primary
Change in Orbitofrontal Cortex (OFC) BOLD Signal During Cocaine Cue Reactivity Task (Pre- vs. Post-TBS)
Measured using fMRI during cocaine cue reactivity task. Percent BOLD signal change in OFC from baseline (Visit 2) to post-TBS (Visit 3). Measured using functional MRI during a cocaine cue reactivity task. The outcome reflects the change in raw BOLD signal in the orbitofrontal cortex (OFC) between baseline and post-TBS sessions. Signal change was calculated by comparing activation during cocaine-related image blocks versus neutral image blocks. Values are reported as raw BOLD signal units (not percentages).
Time frame: From baseline to immediately post-TBS
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Active Theta Burst Stimulation | Change in Orbitofrontal Cortex (OFC) BOLD Signal During Cocaine Cue Reactivity Task (Pre- vs. Post-TBS) | -0.0026 BOLD signal | Standard Deviation 0.008 |
| Sham Theta Burst Stimulation | Change in Orbitofrontal Cortex (OFC) BOLD Signal During Cocaine Cue Reactivity Task (Pre- vs. Post-TBS) | 0.0007 BOLD signal | Standard Deviation 0.0105 |
Primary
Change in POMS Score From Baseline to Post-TBS
Total POMS score measured before and after TBS. Higher scores indicate worse mood.
Time frame: From baseline to immediately post-TBS
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Active Theta Burst Stimulation | Change in POMS Score From Baseline to Post-TBS | 5.53 POMS score | Standard Deviation 27.58 |
| Sham Theta Burst Stimulation | Change in POMS Score From Baseline to Post-TBS | 14.63 POMS score | Standard Deviation 23.32 |