N-acetylcysteine + TBS for Cocaine Use Disorder

(COCA Trial)

Overseen By Bashar W Badran, PhD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Medical University of South Carolina

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 5 weeks

62 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial tests a combination of brain stimulation and a supplement to reduce cocaine cravings and improve brain response. It targets people addicted to cocaine who struggle with cravings and brain reactions to drug-related cues. The treatment works by using magnetic pulses to reset brain activity and a supplement to balance brain chemicals.

Will I have to stop taking my current medications?

The trial requires that participants do not take any psychoactive medications, including anti-seizure medications and medications for ADHD. If you are on these medications, you may need to stop taking them to participate.

What data supports the effectiveness of the treatment N-acetylcysteine + TBS for Cocaine Use Disorder?

Research shows that theta-burst stimulation (TBS), a type of brain stimulation, can reduce brain activity related to drug cravings in cocaine users. Studies have found that TBS can decrease cocaine use and cravings, suggesting it may help people with cocaine use disorder. ^{1 2 3 4 5}

Is the combination of N-acetylcysteine and theta-burst stimulation safe for humans?

N-acetylcysteine (NAC) has been studied in humans for cocaine dependence and is generally considered safe, with some studies showing it can reduce cocaine-seeking behavior. Theta-burst stimulation (TBS) is a non-invasive brain stimulation technique that has been used in research to reduce drug cue reactivity, and while individual responses can vary, it is also generally considered safe in clinical settings. ^{1 2 3 6 7}

How is the treatment N-acetylcysteine + TBS for Cocaine Use Disorder different from other treatments?

This treatment is unique because it combines N-acetylcysteine (NAC), which helps restore balance in brain chemicals like glutamate to reduce cocaine cravings, with theta-burst stimulation (TBS), a type of brain stimulation that may further decrease the brain's response to cocaine cues. This dual approach targets both the chemical and neural aspects of addiction, which is different from treatments that focus solely on one aspect. ^{7 8 9 10 11}

Research Team

All Validations Passed Badran, PhD

Principal Investigator

Medical University of SC

Eligibility Criteria

This trial is for adults aged 18-65 with cocaine use disorder who are fluent in English and currently receiving outpatient treatment for substance issues. Participants must live within 50 miles of the study site, have no history of seizures or metal implants in the head/neck, and not be at risk for MRI-related complications like claustrophobia or certain brain injuries.

Inclusion Criteria

English fluency

Meet criteria for cocaine use disorder (CUD), as determined by DSM-V criteria, using the Structured Clinical Interview for DSM-V

Does not have metal objects in the head/neck

Exclusion Criteria

I have had a head injury or a brain condition that shows up on MRI scans.

You currently have or have had a mental condition called psychosis.

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

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive theta burst stimulation (TBS) and N-acetylcysteine (NAC) to examine effects on cocaine craving and brain response

5 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Decrease Cocaine Cue Reactivity
• N-acetylcysteine
• Neurocircuit Strategy
• Theta-burst stimulation (TBS)

Trial Overview The trial tests whether combining theta burst stimulation (TBS) with N-acetylcysteine (NAC) can reduce cravings and alter brain responses to cocaine cues in individuals with cocaine use disorder. It aims to understand if this combination therapy is more effective than current treatments.

Participant Groups

Group I: Placebo + Theta Burst Stimulation Experimental Treatment 1 Intervention

Group II: N-acetylcysteine + Theta Burst Stimulation Experimental Treatment 2 Interventions

Group III: Placebo + Sham Theta Burst Stimulation Active Control 1 Intervention

Group IV: N-acetylcysteine + Sham Theta Burst Stimulation Placebo Group 1 Intervention

Who Is Running the Clinical Trial?

Medical University of South Carolina

Lead Sponsor

Trials

994

Recruited

7,408,000+

National Institute on Drug Abuse (NIDA)

Collaborator

Trials

2,658

Recruited

3,409,000+

Findings from Research

Bilateral intermittent theta-burst stimulation (iTBS) of the prefrontal cortex showed a long-term therapeutic effect in reducing cocaine use disorder (CUD), with 69.7% of patients remaining abstinent after 12 months following treatment.

Patients who adhered to a maintenance treatment after iTBS had significantly lower dropout rates (29.63%) compared to those who did not follow maintenance (58.82%), highlighting the importance of ongoing treatment for sustaining abstinence.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Role of maintenance treatment on long-term efficacy of bilateral iTBS of the prefrontal cortex in treatment-seeking cocaine addicts: A retrospective analysis. Sanna, A., Bini, V., Badas, P., et al.[2022]

A proof-of-concept study involving 19 individuals with cocaine use disorder showed that administering intermittent theta-burst stimulation (iTBS) to the left dorsolateral prefrontal cortex was well-tolerated and safe, even in participants actively using cocaine.

Participants who completed at least 26 of the 30 iTBS sessions reduced their weekly cocaine use by 78% in spending and 70% in frequency, indicating that iTBS may effectively modulate addiction-related circuits and reduce substance use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Accelerated Intermittent Theta-Burst Stimulation as a Treatment for Cocaine Use Disorder: A Proof-of-Concept Study. Steele, VR., Maxwell, AM., Ross, TJ., et al.[2020]

References

1. Switzerland pubmed.ncbi.nlm.nih.gov

Developing Repetitive Transcranial Magnetic Stimulation (rTMS) as a Treatment Tool for Cocaine Use Disorder: a Series of Six Translational Studies. [2022]

2. United States pubmed.ncbi.nlm.nih.gov

Transdiagnostic Effects of Ventromedial Prefrontal Cortex Transcranial Magnetic Stimulation on Cue Reactivity. [2021]

3. Switzerland pubmed.ncbi.nlm.nih.gov

State-Dependent Effects of Ventromedial Prefrontal Cortex Continuous Thetaburst Stimulation on Cocaine Cue Reactivity in Chronic Cocaine Users. [2020]

4. Switzerland pubmed.ncbi.nlm.nih.gov

Role of maintenance treatment on long-term efficacy of bilateral iTBS of the prefrontal cortex in treatment-seeking cocaine addicts: A retrospective analysis. [2022]

5. Switzerland pubmed.ncbi.nlm.nih.gov

Accelerated Intermittent Theta-Burst Stimulation as a Treatment for Cocaine Use Disorder: A Proof-of-Concept Study. [2020]

6. Ireland pubmed.ncbi.nlm.nih.gov

N-acetylcysteine for treating cocaine addiction - A systematic review. [2019]

7. United States pubmed.ncbi.nlm.nih.gov

N-acetylcysteine reduces cocaine-seeking behavior and anterior cingulate glutamate/glutamine levels among cocaine-dependent individuals. [2023]

8. United States pubmed.ncbi.nlm.nih.gov

N-Acetylcysteine reduces early- and late-stage cocaine seeking without affecting cocaine taking in rats. [2022]

9. United States pubmed.ncbi.nlm.nih.gov

The effect of N-acetylcysteine on brain glutamate and gamma-aminobutyric acid concentrations and on smoking cessation: A randomized, double-blind, placebo-controlled trial. [2018]

10. Ireland pubmed.ncbi.nlm.nih.gov

N-Acetylcysteine reduces cocaine-cue attentional bias and differentially alters cocaine self-administration based on dosing order. [2019]

11. United States pubmed.ncbi.nlm.nih.gov

The effect of N-acetylcysteine in the nucleus accumbens on neurotransmission and relapse to cocaine. [2021]