Neurocircuit Strategy to Decrease Cocaine Cue Reactivity (COCA)

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.

Study Overview

• Status: Recruiting
• Conditions: Cocaine-Related Disorders
• Intervention / Treatment: Drug: N-acetylcysteine; Device: Theta-burst stimulation (TBS)

• Study Type: Interventional
• Enrollment (Anticipated): 96
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Bashar Badran, PhD; Phone Number: 843-792-6076; Email: badran@musc.edu

Study Locations

• United States
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Recruiting
      • Medical University of South Carolina
      • Contact: Hesheng Liu, PhD; Phone Number: 843-792-2528; Email: liuhe@musc.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: N-acetylcysteine + Theta Burst Stimulation	Drug: 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.; Other Names: NAC; Device: 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.
Sham Comparator: N-acetylcysteine + Sham Theta Burst Stimulation	Drug: 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.; Other Names: NAC
Experimental: Placebo + Theta Burst Stimulation	Device: 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.
No Intervention: Placebo + Sham Theta Burst Stimulation

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Magnitude of change in fMRI brain response to images from TBS	Measure the effects of neural stimulation on MRI brain response to drug-related cues	5 weeks
Magnitude of change in brain functional connectivity	Measure the effects of N-Acetylcysteine on MRI brain functional connectivity	5 weeks
Magnitude of change in fMRI brain response to images from NAC	Measure the combined effects of neural stimulation and N-Acetylcysteine on brain response to drug-related cues.	5 weeks

Collaborators and Investigators

• Sponsor: Medical University of South Carolina
• Collaborators: National Institute on Drug Abuse (NIDA)
• Investigators: Principal Investigator: All Validations Passed Badran, PhD, Medical University of SC

Study record dates

Study Major Dates

• Study Start (Actual): December 18, 2020
• Primary Completion (Anticipated): November 30, 2024
• Study Completion (Anticipated): December 31, 2024

Study Registration Dates

• First Submitted: November 5, 2019
• First Submitted That Met QC Criteria: November 5, 2019
• First Posted (Actual): November 7, 2019

Study Record Updates

• Last Update Posted (Actual): March 29, 2023
• Last Update Submitted That Met QC Criteria: March 28, 2023
• Last Verified: March 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Chemically-Induced Disorders; Substance-Related Disorders; Cocaine-Related Disorders; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Protective Agents; Respiratory System Agents; Antioxidants; Antidotes; Free Radical Scavengers; Expectorants; Acetylcysteine; N-monoacetylcystine
• Other Study ID Numbers: 00091981; 5P50DA046373-04 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: Yes