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Transdermal Rotigotine as Adjunct to Behavioral Therapy for Cocaine Use Disorder

Primary Purpose

Substance-Related Disorders

Status
Recruiting
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Rotigotine Transdermal System [Neupro]
Placebo
Sponsored by
Virginia Commonwealth University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Substance-Related Disorders

Eligibility Criteria

18 Years - 55 Years (Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: Male or female subjects between 18 and 55 years of age. Meet current DSM-5 criteria for Cocaine Use Disorder (CocUD), moderate or severe Currently undergoing treatment as usual for CocUD (such as individual or group therapy sessions), or slated for enrollment in a program for CocUD treatment as usual. 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). 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. Exclusion Criteria: 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. Use of medications contraindicated for concurrent use along with rotigotine. These include dopamine antagonists such as antipsychotic medications (especially neuroleptics) or metoclopramide. Subjects with evidence or history of any clinically significant medical disorder including biliary obstruction, 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. 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. Have metal fragments or other bodily metal (e.g., pacemaker) or significant claustrophobia that would put the subjects at risk for MRI scanning. Be allergic to rotigotine. Have taken any investigational drug within 45 days prior to baseline Show clinically significant symptoms of cocaine or opioid withdrawal 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

Sites / Locations

  • Virginia Commonwealth UniversityRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Active Rotigotine (RTG)

Placebo

Arm Description

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

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

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

executive function (change)
Change in CNS-VS Neurocognition Index (NCI) scores
QoLI total score (change)
Change in QoLI total scores
dorsolateral prefrontal cortex (DLPFC)
Change in recruitment of dorsolateral prefrontal cortex (DLPFC)
stop signal task (SST)
Change in recruitment of right anterior insula by stop-signals in the SST
EC from DLPFC to striatum during working memory demands
change in EC from DLPFC to striatum during working memory demands in the EFNBk and during resting state

Full Information

First Posted
April 27, 2023
Last Updated
September 18, 2023
Sponsor
Virginia Commonwealth University
Collaborators
National Institute on Drug Abuse (NIDA)
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1. Study Identification

Unique Protocol Identification Number
NCT05886582
Brief Title
Transdermal Rotigotine as Adjunct to Behavioral Therapy for Cocaine Use Disorder
Official Title
Phase 2a Double-Blind Placebo-Controlled Trial of Transdermal Rotigotine as Adjunct to Behavioral Therapy for Cocaine Use Disorder
Study Type
Interventional

2. Study Status

Record Verification Date
September 2023
Overall Recruitment Status
Recruiting
Study Start Date
September 11, 2023 (Actual)
Primary Completion Date
June 2026 (Anticipated)
Study Completion Date
June 2026 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Virginia Commonwealth University
Collaborators
National Institute on Drug Abuse (NIDA)

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

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.
Detailed Description
Among different substance use disorders, stimulant use disorders are more consistently linked with impaired executive function (EF) of the brain, which is a set of cognitive skills like working memory that operate to enable self-control over behavior and long-term planning. Medications such as stimulants that increase function of the frontal cortex dopamine (DA) system can improve EF. However, stimulants such as amphetamine have abuse potential. Of interest is determining whether a multiple DA receptor medication like rotigotine could improve brain function in persons with stimulant use disorder who are in therapy, to help them retain educational concepts and strategies better. Rotigotine has been shown to improve cognition-related quality of life in persons with Alzheimer's Disease. This is a roughly six week trial of rotigotine (given in a skin patch) to determine whether it not only reduces cocaine use in persons in treatment for cocaine use disorder, but actually improves cognitive performance itself, and increases activity in the frontal cortex of the brain, compared to placebo. It is hypothesized that rotigotine will be specifically helpful for cognition and abstinence in those participants whose cognitive performance ability tested at baseline is below the median.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Substance-Related Disorders

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
60 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Active Rotigotine (RTG)
Arm Type
Experimental
Arm Description
Participants who are randomized to the active RTG arm will receive Neupro® RTG patches
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Participants who are randomized to placebo will receive transdermal patches that match the size and color of active Neupro®.
Intervention Type
Drug
Intervention Name(s)
Rotigotine Transdermal System [Neupro]
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Placebo drug
Primary Outcome Measure Information:
Title
Cocaine-positive urine samples
Description
comparison of cocaine-positive urine samples between participants randomized to transdermal RTG relative to participants randomized to placebo patches
Time Frame
weeks 5 - 6 of transdermal patch treatment
Title
self-reported cocaine use
Description
comparison of cocaine cocaine use (by self report) between participants randomized to transdermal RTG relative to participants randomized to placebo patches
Time Frame
weeks 5 - 6 of transdermal patch treatment
Secondary Outcome Measure Information:
Title
executive function (change)
Description
Change in CNS-VS Neurocognition Index (NCI) scores
Time Frame
change from baseline to study week 6
Title
QoLI total score (change)
Description
Change in QoLI total scores
Time Frame
change from baseline to study week 6
Title
dorsolateral prefrontal cortex (DLPFC)
Description
Change in recruitment of dorsolateral prefrontal cortex (DLPFC)
Time Frame
study day 1 to study week 6
Title
stop signal task (SST)
Description
Change in recruitment of right anterior insula by stop-signals in the SST
Time Frame
study day 1 to study week 6
Title
EC from DLPFC to striatum during working memory demands
Description
change in EC from DLPFC to striatum during working memory demands in the EFNBk and during resting state
Time Frame
study day 1 to study week 6

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
55 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Male or female subjects between 18 and 55 years of age. Meet current DSM-5 criteria for Cocaine Use Disorder (CocUD), moderate or severe Currently undergoing treatment as usual for CocUD (such as individual or group therapy sessions), or slated for enrollment in a program for CocUD treatment as usual. 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). 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. Exclusion Criteria: 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. Use of medications contraindicated for concurrent use along with rotigotine. These include dopamine antagonists such as antipsychotic medications (especially neuroleptics) or metoclopramide. Subjects with evidence or history of any clinically significant medical disorder including biliary obstruction, 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. 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. Have metal fragments or other bodily metal (e.g., pacemaker) or significant claustrophobia that would put the subjects at risk for MRI scanning. Be allergic to rotigotine. Have taken any investigational drug within 45 days prior to baseline Show clinically significant symptoms of cocaine or opioid withdrawal 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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Kameron Simmons
Phone
(804) 827-3784
Email
simmonsk5@vcu.edu
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
James M Bjork, PhD
Organizational Affiliation
Virginia Commonwealth University
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Albert Arias, MD
Organizational Affiliation
Virginia Commonwealth University
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Tanya Ramey, PHD
Organizational Affiliation
National Institute on Drug Abuse (NIDA)
Official's Role
Study Director
Facility Information:
Facility Name
Virginia Commonwealth University
City
Richmond
State/Province
Virginia
ZIP/Postal Code
23284
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Kameron Simmons
Phone
804-828-3686
Email
Simmonsk5@vcu.edu
First Name & Middle Initial & Last Name & Degree
James M Bjork, PhD
First Name & Middle Initial & Last Name & Degree
Albert Arias, MD

12. IPD Sharing Statement

Plan to Share IPD
No

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Transdermal Rotigotine as Adjunct to Behavioral Therapy for Cocaine Use Disorder

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