Transdermal Rotigotine as Adjunct to Behavioral Therapy for Cocaine Use Disorder

NCT05886582 | Recruiting Phase 2 DMC FDA Drug

• 2 other identifiers: HM200269101U01DA057846-01
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Substance-Related Disorders

Outcome Measures

Primary Outcomes (2)

• Cocaine-positive urine samples

  comparison of cocaine-positive urine samples between participants randomized to transdermal RTG relative to participants randomized to placebo patches

  weeks 5 - 6 of transdermal patch treatment

• self-reported cocaine use

  comparison of cocaine cocaine use (by self report) between participants randomized to transdermal RTG relative to participants randomized to placebo patches

  weeks 5 - 6 of transdermal patch treatment

Secondary Outcomes (5)

• executive function (change)

  change from baseline to study week 6

• QoLI total score (change)

  change from baseline to study week 6

• dorsolateral prefrontal cortex (DLPFC)

  study day 1 to study week 6

• stop signal task (SST)

  study day 1 to study week 6

• EC from DLPFC to striatum during working memory demands

  study day 1 to study week 6

Study Arms (2)

Active Rotigotine (RTG)

EXPERIMENTAL

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

Drug: Rotigotine Transdermal System [Neupro]

Placebo

PLACEBO COMPARATOR

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

Drug: Placebo

Interventions

Rotigotine Transdermal System [Neupro] DRUG

Neupro® 2mg/24h transdermal patches for the first seven days, followed by the target 4mg dose for the subsequent 35 days (five weeks) of dosing up to the follow-up assessments, followed by two days of 2mg/24h ramp-down dose.

Active Rotigotine (RTG)

Placebo DRUG

Placebo drug

Placebo

Eligibility Criteria

• Age: 25 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female subjects between 25 and 70 years of age.
• Meet current DSM-5 criteria for Cocaine Use Disorder (CocUD), moderate or severe
• Able to understand and comply with study procedures
• Have positive urine result for cocaine metabolite benzoylecgonine (BE) during at least one screening visit (out of up to three visits, depending on participants' preference) AND/OR self-report of recent cocaine use (approximately past 30 days).
• Have hematology and chemistry laboratory tests that are within normal limits, except that liver function tests must be no more than 2x of the upper limit of normal (if any elevation is above the limit - must be judged by the study physician to be clinically insignificant).
• No clinically significant abnormalities on baseline ECG.
• Be able to demonstrate an understanding of study procedures and follow instructions including behavioral laboratory and fMRI testing.
• Women must either be unable to conceive (i.e., surgically sterilized, sterile, or postmenopausal) or be using a reliable form of contraception (e.g., abstinence, birth control pills, intrauterine device with spermicide, or condoms). Men will be advised to use condoms. All females must provide negative pregnancy urine tests before study entry, at each visit during the study, and the end of study participation.
• Body Mass Index (BMI) between 18-45kg/M2 and weight of at least 50kg at screening

You may not qualify if:

• Have concurrent secondary DSM-5 diagnosis of any psychoactive substance use disorder other than cocaine, alcohol, methamphetamine, nicotine, opioid, or marijuana use disorder.
• Have a DSM-5 axis I psychiatric disorder other than substance use disorder, including but not limited to Bipolar I Disorder, Schizophrenia, or other psychotic disorder that require treatment with antipsychotics, or a neurological disorder requiring ongoing treatment and/or making study participation unsafe. Comorbid PTSD, Generalized Anxiety Disorder and Major Depressive Disorder will be allowed.
• Consistent and regular (as opposed to intermittent, infrequent, or as needed) use of medications contraindicated for concurrent use along with RTG, or would confound the mechanism of RTG action and data interpretation. These include DA antagonists such as antipsychotic medications (especially neuroleptics) or metoclopramide.
• Subjects with evidence or history of any clinically significant medical disorder including biliary obstruction, clinically significant hepatic disease, severe cardiovascular or pulmonary disease, bronchial asthma, renal, or endocrine disease. However, controlled hypertension, controlled hypothyroidism, and cancer in remission over 5 years will not be excluded.
• Have a history of seizures (excluding childhood febrile seizures) or loss of consciousness (e.g. from traumatic brain injury) for more than 30 minutes.
• Have significant current suicidal or homicidal ideation or a suicide attempt within the past 6 months, based on the Columbia Suicide Severity Rating Scale (C-SSRS).
• Be HIV positive by self-report or history.
• Be pregnant or nursing or not using a reliable form of contraception if able to conceive. All females must provide negative pregnancy urine tests before study entry, at each visit during the study, and the end of study participation
• Have any other illness, or condition, which in the opinion of the clinical co-investigator (Arias) would preclude safe and/or successful completion of the study.
• Be allergic to rotigotine.
• Have taken any investigational drug within 45 days prior to baseline
• Demonstrate intolerance to, poor adherence to, or extreme skin irritation by daily application of known placebo "practice" skin patches during the screening phase
• Current/pending criminal charges that may result in incarceration within the next 60 days
• Self-report of allergic or other reactions to sulfites (e.g. in foods)

Sponsors & Collaborators

• Virginia Commonwealth University: lead
• National Institute on Drug Abuse (NIDA): collaborator

Study Sites (1)

Virginia Commonwealth University

Richmond, Virginia, 23284, United States

RECRUITING

MeSH Terms

Conditions

Substance-Related Disorders

Interventions

rotigotine

Condition Hierarchy (Ancestors)

Chemically-Induced Disorders; Mental Disorders

Study Officials

• James M Bjork, PhD

  Virginia Commonwealth University

  PRINCIPAL INVESTIGATOR

• Albert Arias, MD

  Virginia Commonwealth University

  PRINCIPAL INVESTIGATOR

• Tanya Ramey, PHD

  National Institute on Drug Abuse (NIDA)

  STUDY DIRECTOR

Central Study Contacts

Tiffany Pignatello, FNP

CONTACT

(804) 827-3784; study4u@vcu.edu

Lori Keyser-Marcus, PhD

CONTACT

804-828-3686; study4u@vcu.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 27, 2023
• First Posted: June 2, 2023
• Study Start: September 11, 2023
• Primary Completion (Estimated): June 1, 2026
• Study Completion (Estimated): June 1, 2026
• Last Updated: September 29, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)