Neurocircuit Strategy to Decrease Cocaine Cue Reactivity

NCT04155632 | Completed Phase 2 Results FDA Drug FDA Device

• 2 other identifiers: 000919815P50DA046373-04
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 1

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.

Conditions

Cocaine-Related Disorders

Outcome Measures

Primary Outcomes (3)

• 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).

  From baseline to immediately post-TBS

• Change in POMS Score From Baseline to Post-TBS"

  Total POMS score measured before and after TBS. Higher scores indicate worse mood.

  From baseline to immediately post-TBS

• 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.

  From baseline to immediately post-TBS

Study Arms (4)

N-acetylcysteine + Theta Burst Stimulation

EXPERIMENTAL

Drug: N-acetylcysteine; Device: Theta-burst stimulation (TBS)

N-acetylcysteine + Sham Theta Burst Stimulation

SHAM COMPARATOR

Drug: N-acetylcysteine

Placebo + Theta Burst Stimulation

EXPERIMENTAL

Device: Theta-burst stimulation (TBS)

Placebo + Sham Theta Burst Stimulation

NO INTERVENTION

Interventions

N-acetylcysteine DRUG

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.

Also known as: NAC

N-acetylcysteine + Sham Theta Burst Stimulation; N-acetylcysteine + Theta Burst Stimulation

Theta-burst stimulation (TBS) DEVICE

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.

N-acetylcysteine + Theta Burst Stimulation; Placebo + Theta Burst Stimulation

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• \. 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.
• \. 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.
• \. 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.
• \. Does not have a history of claustrophobia leading to significant clinical anxiety symptoms.

You may not qualify if:

• Past head injury or primary neurological disorder associated with MRI abnormalities, including dementia, MCI, brain tumors, epilepsy, Parkinson's disease, or demyelinating diseases
• Any physical or intellectual disability affecting completion of assessments
• Any contraindication to MRI
• Current or past psychosis
• ECT in last 6 months
• Clinical Institute Withdrawal Assessment (CIWA-Ar) scale will be used to assess alcohol withdrawal. Individuals with CIWA \> 8 will be excluded.
• Individuals with unstable medical illness (e.g., hypertension, diabetes, myocardial infarction)
• Has current suicidal ideation or homicidal ideation.
• Has the need for maintenance or acute treatment with any psychoactive medication including anti-seizure medications and medications for ADHD
• Suffers from chronic migraines
• Any physical or intellectual disability affecting completion of assessments

Sponsors & Collaborators

• Medical University of South Carolina: lead
• National Institute on Drug Abuse (NIDA): collaborator

Study Sites (1)

Medical University of South Carolina

Charleston, South Carolina, 29425, United States

Location

MeSH Terms

Conditions

Cocaine-Related Disorders

Interventions

Acetylcysteine

Condition Hierarchy (Ancestors)

Substance-Related Disorders; Chemically-Induced Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Cysteine; Amino Acids, Sulfur; Sulfur Compounds; Organic Chemicals; Amino Acids; Amino Acids, Peptides, and Proteins

Limitations and Caveats

We only investigate a single session of cTBS in participants with CUD. Repeated cTBS sessions may produce long-lasting changes in craving and relapse prevention, which should be explored in future research.

Results Point of Contact

• Title: Dr. Xiaolong Peng
• Organization: Medical University of South Carolina

pengxi@musc.edu

8437928642

Study Officials

• All Validations Passed Badran, PhD

  Medical University of SC

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 5, 2019
• First Posted: November 7, 2019
• Study Start: December 18, 2020
• Primary Completion: March 9, 2023
• Study Completion: March 9, 2023
• Last Updated: September 24, 2025
• Results First Posted: September 24, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)