- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01739192
A Novel Anti-Obesity Drug Combination as a Pharmacotherapy for Cocaine Dependence
Study Overview
Detailed Description
Cocaine (COC) dependence is a significant public health concern. A widely effective pharmacotherapy has not yet been identified for COC dependence. Innovative strategies are needed to identify an effective pharmacotherapy for COC dependence. Testing medications effective for disorders that share neurobiological substrates with drug dependence, for example, could yield treatments for managing COC dependence.
Obesity is also a significant public health concern. Although obesity and COC dependence are typically considered distinct clinical entities, both diseases involve perturbations of central biogenic amine and/or hypothalamic-melanocortin systems. The obesity epidemic has spurred development of medications to promote weight loss. A combination of bupropion (BUP) and naltrexone (NTX) is effective for obesity. The overarching goal of this application is to demonstrate the initial efficacy, safety, and tolerability of BUP-NTX combinations for COC dependence. A mixed-model experiment will be conducted in which separate cohorts of non-treatment-seeking, COC-dependent participants will be randomized to different maintenance doses of NTX (i.e., NTX is a between-subject factor). Participants (N=12) in each NTX cohort will be maintained concurrently on BUP (i.e., BUP is a within-subject factor). The reinforcing effects of intranasal COC will be determined after participants in each NTX cohort are maintained for 4-7 days on each of the BUP doses (i.e., COC is a within-subject factor). COC (0, 40 and 80 mg) will be tested with multiple dose combinations of BUP (0, 100, 200, 400 mg/day) and NTX (0, 25, 50 mg/day). The proposed study will also identify the optimal dose combination of BUP and NTX that most effectively attenuates the reinforcing effects of COC.
This research will provide critical information regarding the initial efficacy and optimal doses of a novel drug combination, BUP and NTX, for COC dependence, which will enhance the probability of success when advanced to a clinical trial. Innovations of the proposed research include: 1) testing a combination of marketed drugs that demonstrated modest efficacy when tested as mono-therapies; 2) the use of a sophisticated drug self-administration procedure; 3) providing the impetus for the conduct of a Phase II clinical trial to further demonstrate the efficacy of BUP-NTX combinations for COC dependence; and 4) demonstrating the initial efficacy and optimal doses of a combination of commercially available drugs, as opposed to waiting for novel molecules to be available for testing in humans, thereby impacting clinical research and practice more quickly. In these ways, the proposed project will shift the current clinical research paradigm in pharmacotherapy development and have a significant impact on the treatment of COC dependence.
Study Type
Enrollment (Actual)
Phase
- Early Phase 1
Contacts and Locations
Study Locations
-
-
Kentucky
-
Lexington, Kentucky, United States, 40536-0086
- University of Kentucky Medical Center
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Recent cocaine use
Exclusion Criteria:
- Abnormal screening outcome (e.g., ECG, blood chemistry result) that study physicians deem clinically significant.
- Current or past histories of substance abuse or dependence that are deemed by the study physicians to interfere with study completion.
- History of serious physical disease, current physical disease, impaired cardiovascular functioning, chronic obstructive pulmonary disease, history of seizure or current or past histories of serious psychiatric disorder that in the opinion of the study physician would interfere with study participation will be excluded from participation.
- Females not currently using effective birth control.
- Contraindications to cocaine, bupropion or naltrexone,
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Basic Science
- Allocation: Randomized
- Interventional Model: Factorial Assignment
- Masking: Triple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Placebo Comparator: Arm 1
Placebo oral daily for approximately six (6) weeks.
|
Subjects will be maintained on oral bupropion or placebo during the study.
|
Experimental: Arm 2
Naltrexone (25 mg) oral daily for approximately six (6) weeks.
|
Subjects will be maintained on oral bupropion or placebo during the study.
|
Experimental: Arm 3
Naltrexone (50 mg) oral daily for approximately six (6) weeks.
|
Subjects will be maintained on oral bupropion or placebo during the study.
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Reinforcing Effects
Time Frame: Twelve (12) times over approximately six (6) weeks inpatient admission.
|
The reinforcing effects of cocaine will be determined using a self-administration procedure in which subjects choose to take previously sampled doses.
Reinforcing effects are measured during maintenance on placebo, bupropion, naltrexone, and bupropion-naltrexone combinations.
|
Twelve (12) times over approximately six (6) weeks inpatient admission.
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Subjective effects
Time Frame: Twelve (12) times over approximately six (6) weeks inpatient admission.
|
Subjects will complete subjective effects measures during sessions while they are admitted to our inpatient unit.
These items will ask about drug effects and general mood.
|
Twelve (12) times over approximately six (6) weeks inpatient admission.
|
Physiological and side effects.
Time Frame: Daily over approximately six (6) weeks inpatient admission.
|
Physiological and side effects measures will be completed daily while subjects are admitted to our inpatient unit.
Physiological measures included heart rate and blood pressure.
Side effects questions will query subjects about common effects of centrally active medications.
|
Daily over approximately six (6) weeks inpatient admission.
|
Collaborators and Investigators
Sponsor
Collaborators
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Physiological Effects of Drugs
- Neurotransmitter Agents
- Molecular Mechanisms of Pharmacological Action
- Enzyme Inhibitors
- Psychotropic Drugs
- Neurotransmitter Uptake Inhibitors
- Membrane Transport Modulators
- Antidepressive Agents
- Dopamine Agents
- Cytochrome P-450 Enzyme Inhibitors
- Antidepressive Agents, Second-Generation
- Cytochrome P-450 CYP2D6 Inhibitors
- Dopamine Uptake Inhibitors
- Bupropion
Other Study ID Numbers
- R01DA032254 (U.S. NIH Grant/Contract)
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Cocaine Use Disorders
-
New York State Psychiatric InstituteNational Institute on Drug Abuse (NIDA); Columbia UniversityNot yet recruitingCocaine Use Disorder | Cocaine Dependence | Cocaine Use | Cocaine Use Disorder, Moderate | Cocaine Use Disorder, Severe
-
Medical University of South CarolinaNational Institute on Drug Abuse (NIDA)Active, not recruitingMethamphetamine Use Disorder | Cocaine Use Disorder | Cocaine Dependence | Methamphetamine Dependence | Stimulant Use Disorder | Methamphetamine Abuse | Cocaine Abuse | Stimulant Abuse | Stimulant UseUnited States
-
Midwest Biomedical Research FoundationNational Institute on Drug Abuse (NIDA)CompletedCocaine Use DisordersUnited States
-
New York State Psychiatric InstituteCompletedCocaine Use DisordersUnited States
-
National Institute on Drug Abuse (NIDA)The University of Texas Health Science Center, HoustonCompleted
-
Midwest Biomedical Research FoundationUnknown
-
William StoopsNational Institute on Drug Abuse (NIDA)CompletedCocaine Use DisordersUnited States
-
Friends Research Institute, Inc.National Institute on Drug Abuse (NIDA)RecruitingOpioid Use Disorder | Opioid Use | Cocaine Use Disorder | Cocaine UseUnited States
-
University of Maryland, BaltimoreNational Institute on Drug Abuse (NIDA)Withdrawn
-
University of Maryland, BaltimoreNational Institute on Drug Abuse (NIDA)Completed
Clinical Trials on Bupropion
-
Orexigen Therapeutics, IncCompleted
-
University of Rochester NCORP Research BaseNational Cancer Institute (NCI)RecruitingBe Diagnosed With Cancer and Have Completed Systemic TherapyUnited States
-
Altschuler, Eric, M.D.GlaxoSmithKlineCompleted
-
Alembic Pharmaceuticals Ltd.CompletedBioequivalenceCanada
-
Mayo ClinicNational Institute on Alcohol Abuse and Alcoholism (NIAAA)Completed
-
University of Wisconsin, MadisonNational Institutes of Health (NIH)Completed
-
University of Sao Paulo General HospitalFundação de Amparo à Pesquisa do Estado de São PauloCompletedSmoking Cessation | Genetic PredispositionBrazil
-
NRG OncologyNational Cancer Institute (NCI)CompletedBreast Carcinoma | Cervical Carcinoma | Vaginal Carcinoma | Ovarian Carcinoma | Uterine Corpus Cancer | Vulvar Carcinoma | PostmenopausalUnited States
-
University of Wisconsin, MadisonNational Institute on Drug Abuse (NIDA); National Cancer Institute (NCI)Completed
-
M.D. Anderson Cancer CenterNational Cancer Institute (NCI)RecruitingCigarette Smoking-Related CarcinomaUnited States