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

Must not be taking: Psychoactive, Anti-seizure, ADHD meds

Disqualifiers: Psychosis, Pregnancy, Unstable illness, others

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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to evaluate the effectiveness of combining N-acetylcysteine, a supplement that may reduce cravings, with theta burst stimulation, a type of brain stimulation, in reducing cocaine cravings and altering brain responses to cocaine-related images. Researchers will divide participants into groups to test various combinations of these treatments and a placebo. Individuals diagnosed with cocaine use disorder who are currently in a treatment program may be suitable candidates for this trial. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group, providing participants an opportunity to contribute to significant advancements in addiction treatment.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that N-acetylcysteine (NAC) is generally safe and well-tolerated. Studies have found that people who use cocaine can take NAC without major problems, and some reports suggest it might help ease withdrawal symptoms. Theta burst stimulation (TBS) also maintains a good safety record. It has been tested with people who use cocaine, and results indicate it's safe without major side effects. Both NAC and TBS have been studied for their effects on cocaine cravings and brain response, appearing manageable for participants.

In summary, both NAC and TBS are well-tolerated, including by those with cocaine use disorder. Serious side effects are uncommon, making them promising options for those interested in joining clinical trials. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for cocaine use disorder because they combine N-acetylcysteine, an antioxidant, with theta-burst stimulation (TBS), a form of non-invasive brain stimulation. Unlike traditional treatments like behavioral therapy or medications that target dopamine pathways, this approach aims to reduce cocaine cravings by altering brain circuits linked to addiction. The use of TBS is particularly intriguing because it can modulate brain activity quickly and might enhance the effectiveness of N-acetylcysteine in reducing cue reactivity. This dual approach could offer a novel and potentially faster-acting solution for individuals struggling with cocaine addiction.

What evidence suggests that this trial's treatments could be effective for cocaine use disorder?

This trial will evaluate the combination of N-acetylcysteine (NAC) with theta burst stimulation (TBS) for treating cocaine use disorder. Research has shown that using NAC with TBS might help reduce cocaine cravings. Studies have found that TBS can decrease brain activity related to drug cravings in people who use cocaine. NAC may help with withdrawal symptoms by reducing the brain's reaction to cocaine triggers. Applying TBS to certain brain areas has also lessened cravings and drug use. Early results suggest that these treatments might work better together than individually for treating cocaine use disorder. Participants in this trial will be assigned to different arms, including NAC with TBS, NAC with sham TBS, placebo with TBS, and placebo with sham TBS, to evaluate the effectiveness of these combinations. ^{1 2 3 4 5}

Who Is on the Research Team?

All Validations Passed Badran, PhD

Principal Investigator

Medical University of SC

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

Citations

1. nature.com nature.com/articles/s41386-023-01776-0

A systematic review and meta-analysis of neuromodulation ... Left frontal pole theta burst stimulation decreases orbitofrontal and insula activity in cocaine users and alcohol users. Drug Alcohol Depend.

2. frontiersin.org frontiersin.org/journals/psychiatry/articles/10.3389/fpsyt.2024.1489194/full

N-acetylcysteine reduces prefrontal reactivity to cocaine ... Our findings show that prefrontal reactivity to cocaine cues can be reduced even by a brief pharmacological challenge with N-acetylcysteine.

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC1513138/

Safety and Tolerability of N-Acetylcysteine in Cocaine- ... These preliminary results suggest that NAC is well tolerated in healthy, cocaine-dependent individuals and may reduce cocaine-related withdrawal symptoms and ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT04155632

Neurocircuit Strategy to Decrease Cocaine Cue Reactivity 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 ...

5. withpower.com withpower.com/trial/phase-3-cocaine-related-disorders-11-2020-b306a

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 ...