Rotigotine + Behavioral Therapy for Cocaine Use Disorder

Overseen By Albert Arias, MD

Age: 18 - 65

Sex: Any

Trial Phase: Phase 2

Sponsor: Virginia Commonwealth University

Must not be taking: Antipsychotics, Metoclopramide

Disqualifiers: Psychoactive disorders, Seizures, HIV, others

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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 6 weeks

60 Participants Needed

Trial Summary

What is the purpose of this trial?

This is a randomized, double-blind, placebo-controlled phase 2b pilot clinical trial to determine whether non-ergoline D3/D2/D1 dopamine (DA) receptor agonist rotigotine (RTG), in combination with treatment as usual, including individual or group behavioral therapy can a) reduce cocaine use and also b) increase brain activity in frontocortical areas of the brain, and, as a reflection of that - improve top-down cognitive control in persons with cocaine use disorder (CocUD). Rotigotine is a marketed non-ergoline D3/D2/D1 DA agonist (RTG, Neupro®) in the form of a transdermal patch that is FDA-approved for the treatment of Parkinson's Disease and Restless Legs Syndrome. The premise of this project was based on apparent beneficial effects of RTG in a different human population characterized by executive function (EF) impairment. In light of the deficits in EF common in persons with CocUD, RTG may hold the potential for cognitive improvement in persons with CocUD who are in treatment as usual to both attend to and retain psychoeducation concepts better. In addition, rotigotine may help these individuals in recovery maintain goals better, where goal maintenance is a crucial integrative product of successful EF.

Will I have to stop taking my current medications?

The trial does not specify if you must stop taking your current medications, but you cannot use medications that are not safe to take with rotigotine, like certain antipsychotics or metoclopramide.

What data supports the effectiveness of the drug Rotigotine Transdermal System for treating cocaine use disorder?

There is no direct evidence from the provided research articles supporting the effectiveness of Rotigotine for cocaine use disorder. However, the research highlights the importance of targeting dopamine pathways in treating cocaine addiction, which is relevant since Rotigotine affects dopamine levels. ^{1 2 3 4 5}

How does the drug Rotigotine differ from other treatments for cocaine use disorder?

Rotigotine is unique because it is a dopamine agonist, meaning it mimics dopamine in the brain, which may help reduce cravings and withdrawal symptoms associated with cocaine use disorder. Unlike other treatments that focus on blocking cocaine's effects or managing withdrawal symptoms, Rotigotine directly stimulates dopamine receptors, potentially offering a novel approach to managing this condition. ^{1 4 6 7 8}

Research Team

Tanya Ramey, PHD

Principal Investigator

National Institute on Drug Abuse (NIDA)

James M Bjork, PhD

Principal Investigator

Virginia Commonwealth University

Albert Arias, MD

Principal Investigator

Virginia Commonwealth University

Eligibility Criteria

Adults aged 18-55 with moderate to severe Cocaine Use Disorder, currently in or starting behavioral therapy for addiction. They must have a positive test for cocaine metabolite and no significant heart issues. Women should be non-pregnant, non-nursing, and using contraception; men advised to use condoms.

Inclusion Criteria

Able to understand and comply with study procedures

Women must either be unable to conceive or be using a reliable form of contraception

Have positive urine result for cocaine metabolite benzoylecgonine during at least one screening visit

Exclusion Criteria

Recent use of investigational drugs

Pregnant or nursing or not using a reliable form of contraception if able to conceive

I have had seizures or was unconscious for over 30 minutes.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive transdermal rotigotine or placebo patches for approximately six weeks to assess reduction in cocaine use and improvement in cognitive performance

6 weeks

Weekly visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Rotigotine Transdermal System [Neupro]

Trial Overview The trial is testing if the Rotigotine patch (approved for Parkinson's & Restless Legs Syndrome) can reduce cocaine use and improve cognitive control when added to standard behavioral therapy compared to a placebo patch.

Participant Groups

Group I: Active Rotigotine (RTG) Experimental Treatment 1 Intervention

Participants who are randomized to the active RTG arm will receive Neupro® RTG patches

Group II: Placebo Placebo Group 1 Intervention

Participants who are randomized to placebo will receive transdermal patches that match the size and color of active Neupro®.

Who Is Running the Clinical Trial?

Virginia Commonwealth University

Lead Sponsor

Trials

732

Recruited

22,900,000+

National Institute on Drug Abuse (NIDA)

Collaborator

Trials

2,658

Recruited

3,409,000+

Findings from Research

Pharmacotherapy for substance abuse is most effective when combined with psychosocial support, and it should be tailored to the patient's current needs as they navigate cycles of use and abstinence.

New long-acting formulations of agonists and antagonists are being developed to improve treatment compliance, while innovative approaches like vaccines and products targeting the dopamine reuptake system are advancing in clinical trials for cocaine abuse.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Recent advances against substance abuse. Heading, CE.[2007]

In a study involving primarily young, indigent African-American crack cocaine users, adjunct therapies like acupuncture, anticraving medication, and brainwave therapy were tested to improve retention in intensive outpatient treatment, but none showed a direct impact on drug use outcomes.

However, higher dosages of any adjunct therapy were linked to increased days in treatment and more standard treatment sessions attended, which correlated with negative drug test results at follow-up, suggesting that while the adjunct therapies didn't directly reduce drug use, they may help keep patients engaged in treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effectiveness of adjunct therapies in crack cocaine treatment. Richard, AJ., Montoya, ID., Nelson, R., et al.[2022]

The new radioiodinated cocaine analog, [123I]IPT, effectively targets striatal dopamine transporters in nonhuman primates, showing rapid concentration in these brain regions within approximately 25 minutes after injection.

The study demonstrated that 95% of the binding of [123I]IPT is reversible and specifically associated with dopamine transporters, making it a valuable tool for in vivo SPECT imaging to study dopamine-related functions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Striatal dopamine transporter imaging in nonhuman primates with iodine-123-IPT SPECT. Malison, RT., Vessotskie, JM., Kung, MP., et al.[2016]

RTI-113, a selective dopamine uptake inhibitor, showed similar behavioral effects to cocaine but was less potent in increasing response rates in squirrel monkeys, indicating it may have a safer profile for potential therapeutic use.

RTI-113 demonstrated a longer duration of action compared to cocaine and effectively reduced cocaine self-administration, suggesting it could be a promising candidate for treating cocaine abuse with fewer stimulant effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparative behavioral pharmacology of cocaine and the selective dopamine uptake inhibitor RTI-113 in the squirrel monkey. Howell, LL., Czoty, PW., Kuhar, MJ., et al.[2014]

In a 12-week clinical trial involving 94 patients, both amantadine and desipramine showed initial reductions in reported cocaine abuse compared to placebo, but this effect diminished by week 8, indicating limited long-term efficacy.

Despite good treatment retention and compliance, there were no significant differences in cocaine-free urine samples between the medicated groups and placebo, suggesting that these medications may not effectively sustain abstinence in cocaine-abusing methadone-maintained patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacotherapy for cocaine-abusing methadone-maintained patients using amantadine or desipramine. Kosten, TR., Morgan, CM., Falcione, J., et al.[2019]

There are currently no proven effective medications for treating cocaine dependence, but several promising candidates have been identified, including cabergoline, reserpine, sertraline, and tiagabine, which are set for phase II clinical trials.

A novel 'cocaine vaccine' has shown promise in a phase I trial, being well tolerated and producing anti-cocaine antibodies for up to 9 months, indicating a potential new approach to blocking cocaine's effects in the brain.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Agents in development for the management of cocaine abuse. Gorelick, DA., Gardner, EL., Xi, ZX.[2018]

In a study involving 65 crack-cocaine dependent patients, modafinil did not show significant benefits when added to cognitive behavioral therapy (CBT), as it did not improve treatment retention or reduce cocaine use overall.

However, patients who adhered to modafinil treatment for at least 8 weeks experienced greater reductions in cocaine use, suggesting that optimizing adherence could enhance the effectiveness of modafinil in future studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Modafinil in the treatment of crack-cocaine dependence in the Netherlands: Results of an open-label randomised controlled feasibility trial. Nuijten, M., Blanken, P., van den Brink, W., et al.[2018]

Pharmacological treatments for addiction, such as alpha 2-adrenergic agonists (e.g., clonidine) and naltrexone, target different aspects of the addiction cycle, helping to alleviate withdrawal symptoms and reduce drug reinforcement, respectively.

While these medications can effectively support addiction treatment by addressing specific parts of the cycle, they are not standalone solutions and must be combined with behavioral therapies and patient cooperation for comprehensive care.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacological adjuncts in the treatment of opioid and cocaine addicts. Herridge, P., Gold, MS.[2013]

References

1. England pubmed.ncbi.nlm.nih.gov

Recent advances against substance abuse. [2007]

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

Effectiveness of adjunct therapies in crack cocaine treatment. [2022]

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

Striatal dopamine transporter imaging in nonhuman primates with iodine-123-IPT SPECT. [2016]

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

Comparative behavioral pharmacology of cocaine and the selective dopamine uptake inhibitor RTI-113 in the squirrel monkey. [2014]

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

Pharmacotherapy for cocaine-abusing methadone-maintained patients using amantadine or desipramine. [2019]

6. New Zealand pubmed.ncbi.nlm.nih.gov

Agents in development for the management of cocaine abuse. [2018]

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

Modafinil in the treatment of crack-cocaine dependence in the Netherlands: Results of an open-label randomised controlled feasibility trial. [2018]

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

Pharmacological adjuncts in the treatment of opioid and cocaine addicts. [2013]