A Novel Anti-Obesity Drug Combination as a Pharmacotherapy for Cocaine Dependence

This study is currently recruiting participants. (see Contacts and Locations)
Verified September 2014 by University of Kentucky
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Craig Rush, University of Kentucky
ClinicalTrials.gov Identifier:
NCT01739192
First received: November 27, 2012
Last updated: September 10, 2014
Last verified: September 2014
  Purpose

The research proposed in this application will determine the initial efficacy, safety and tolerability of a novel drug combination, bupropion and naltrexone, as a pharmacotherapy for cocaine dependence. A rigorous, inpatient human laboratory study will be conducted. The proposed study is innovative and important because it will provide the impetus for the conduct of double blind, placebo-controlled trials to further demonstrate the efficacy of bupropion-naltrexone combinations for managing cocaine dependence.


Condition Intervention Phase
Cocaine Use Disorders
Drug: Bupropion
Phase 0

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacodynamics Study
Intervention Model: Factorial Assignment
Masking: Double Blind (Subject, Caregiver, Outcomes Assessor)
Primary Purpose: Basic Science

Resource links provided by NLM:


Further study details as provided by University of Kentucky:

Primary Outcome Measures:
  • Reinforcing Effects [ Time Frame: Twelve (12) times over approximately six (6) weeks inpatient admission. ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • Subjective effects [ Time Frame: Twelve (12) times over approximately six (6) weeks inpatient admission. ] [ Designated as safety issue: Yes ]
    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.

  • Physiological and side effects. [ Time Frame: Daily over approximately six (6) weeks inpatient admission. ] [ Designated as safety issue: Yes ]
    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.


Estimated Enrollment: 48
Study Start Date: January 2013
Estimated Study Completion Date: December 2015
Estimated Primary Completion Date: December 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: Arm 1
Placebo oral daily for approximately six (6) weeks.
Drug: Bupropion
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.
Drug: Bupropion
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.
Drug: Bupropion
Subjects will be maintained on oral bupropion or placebo during the study.

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.

  Eligibility

Ages Eligible for Study:   18 Years to 55 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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,
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01739192

Contacts
Contact: Craig R Rush, PhD 859-257-5388 crush2@email.uky.edu

Locations
United States, Kentucky
University of Kentucky Medical Center Recruiting
Lexington, Kentucky, United States, 40536-0086
Contact: William W Stoops, PhD    859-257-5388    william.stoops@uky.edu   
Principal Investigator: Craig R Rush, PhD         
Sub-Investigator: William W Stoops, PhD         
Sponsors and Collaborators
Craig Rush
  More Information

No publications provided

Responsible Party: Craig Rush, Professor, University of Kentucky
ClinicalTrials.gov Identifier: NCT01739192     History of Changes
Other Study ID Numbers: R01 DA032254, R01DA032254
Study First Received: November 27, 2012
Last Updated: September 10, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Substance-Related Disorders
Cocaine-Related Disorders
Chemically-Induced Disorders
Mental Disorders
Bupropion
Anti-Obesity Agents
Antidepressive Agents, Second-Generation
Antidepressive Agents
Psychotropic Drugs
Central Nervous System Agents
Therapeutic Uses
Pharmacologic Actions
Dopamine Uptake Inhibitors
Dopamine Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Neurotransmitter Uptake Inhibitors
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on September 14, 2014