Neurocircuit Strategy to Decrease Cocaine Cue Reactivity

NCT ID: NCT04155632

Last Updated: 2025-09-24

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 32 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-12-18
• Study Completion Date: 2023-03-09

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: TRIPLE

Study Groups

N-acetylcysteine + Theta Burst Stimulation

Group Type: EXPERIMENTAL

N-acetylcysteine

Intervention Type: 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.

Theta-burst stimulation (TBS)

Intervention Type: 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 + Sham Theta Burst Stimulation

Group Type: SHAM_COMPARATOR

N-acetylcysteine

Intervention Type: 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.

Placebo + Theta Burst Stimulation

Group Type: EXPERIMENTAL

Theta-burst stimulation (TBS)

Intervention Type: 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.

Placebo + Sham Theta Burst Stimulation

Group Type: NO_INTERVENTION

No interventions assigned to this group

Interventions

N-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.

Intervention Type: DRUG

Theta-burst stimulation (TBS)

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.

Intervention Type: DEVICE

Other Intervention Names

NAC

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

National Institute on Drug Abuse (NIDA)

NIH

Sponsor Role: collaborator

Medical University of South Carolina

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

All Validations Passed Badran, PhD

Role: PRINCIPAL_INVESTIGATOR

Medical University of SC

Locations

Medical University of South Carolina

Charleston, South Carolina, United States

Countries

United States

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Document Type: Informed Consent Form

View Document

Other Identifiers

5P50DA046373-04

Identifier Type: NIH

Identifier Source: secondary_id

View Link

00091981

Identifier Type: -

Identifier Source: org_study_id