Targeting GABA and Opioid Systems for a Pharmacotherapy for Methamphetamine Abuse

The research proposed in this application will determine the initial efficacy, safety and tolerability of a novel drug combination, oxazepam (Serax®) and naltrexone (Revia®), as a pharmacotherapy for methamphetamine (Desoxyn®) 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 combined oxazepam and naltrexone for managing methamphetamine dependence.

Study Overview

• Status: Completed
• Conditions: Methamphetamine Dependence; Methamphetamine Abuse
• Intervention / Treatment: Drug: Methamphetamine (Desoxyn®)

• Study Type: Interventional
• Enrollment (Actual): 24
• Phase: Early Phase 1

Contacts and Locations

Study Locations

• United States
  • Kentucky
    • Lexington, Kentucky, United States, 40536
      • University of Kentucky Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Lifetime methamphetamine 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 methamphetamine (Desoxyn®), oxazepam (Serax®) or naltrexone (Revia®)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Triple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Arm 1; Subjects will be maintained on oral placebo.	Drug: Methamphetamine (Desoxyn®); The pharmacodynamic effects of methamphetamine (Desoxyn®) will be determined during placebo, oxazepam (Serax®), naltrexone (Revia®) and combined oxazepam and naltrexone maintenance.
Experimental: Arm 2; Subjects will be maintained on oral oxazepam (Serax®).	Drug: Methamphetamine (Desoxyn®); The pharmacodynamic effects of methamphetamine (Desoxyn®) will be determined during placebo, oxazepam (Serax®), naltrexone (Revia®) and combined oxazepam and naltrexone maintenance.
Experimental: Arm 3; Subjects will be maintained on oral naltrexone (Revia®).	Drug: Methamphetamine (Desoxyn®); The pharmacodynamic effects of methamphetamine (Desoxyn®) will be determined during placebo, oxazepam (Serax®), naltrexone (Revia®) and combined oxazepam and naltrexone maintenance.
Experimental: Arm 4; Subjects will be maintained on oral naltrexone (Revia®) and oral oxazepam (Serax®).	Drug: Methamphetamine (Desoxyn®); The pharmacodynamic effects of methamphetamine (Desoxyn®) will be determined during placebo, oxazepam (Serax®), naltrexone (Revia®) and combined oxazepam and naltrexone maintenance.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Reinforcing Effects	The reinforcing effects of methamphetamine 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, oxazepam (Serax®), naltrexone (Revia®), and oxazepam and naltrexone combined.	After at least four days of placebo, oxazepam (Serax®), naltrexone (Revia®) or oxazepam and naltrexone maintenance

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Subjective Effects	Subjects will complete subjective effects measures during six sessions while they are admitted to our inpatient unit. These items will ask about drug effects and general mood.	12 sessions over approximately 4 week inpatient admissions
Physiological and Side Effects	Physiological and side effects measures will be completed daily while subjects are admitted to our inpatient unit. Physiological measures include heart rate and blood pressure. Side Effects questions will query subjects about common effects of centrally active medications.	Daily over approximately 4 week inpatient admissions

Collaborators and Investigators

• Sponsor: University of Kentucky
• Collaborators: National Institute on Drug Abuse (NIDA)

Study record dates

Study Major Dates

• Study Start: October 1, 2013
• Primary Completion (Actual): September 1, 2018
• Study Completion (Actual): September 1, 2018

Study Registration Dates

• First Submitted: October 15, 2013
• First Submitted That Met QC Criteria: October 17, 2013
• First Posted (Estimate): October 22, 2013

Study Record Updates

• Last Update Posted (Actual): September 14, 2018
• Last Update Submitted That Met QC Criteria: September 13, 2018
• Last Verified: September 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Dopamine Agents; Dopamine Uptake Inhibitors; Central Nervous System Stimulants; Sympathomimetics; Adrenergic Uptake Inhibitors; Methamphetamine
• Other Study ID Numbers: R01DA033394 (U.S. NIH Grant/Contract)