Improving Learning-based Treatment of Cocaine Dependence With Medication

• Sponsor: Johns Hopkins University (Other)
• Overall Status: Completed
• CT.gov ID: NCT01526538
• Collaborator: National Institute on Drug Abuse (NIDA) (NIH)
• Enrollment: 52
• Location: 1
• Arms: 2
• Duration (Months): 18
• Patients Per Site Per Month: 2.9

Study Details

Study Description

Brief Summary

This study will test the efficacy of d-cycloserine in enhancing response to learning-based treatment for cocaine dependence, specifically contingency management.

Condition or Disease	Intervention/Treatment	Phase
COCAINE-RELATED DISORDERS	Drug: d-cycloserine; Drug: sugar pill	Phase 2

Detailed Description

Cocaine dependence is a public health problem with substantial morbidity, however no effective pharmacotherapy for cocaine dependence has been approved by the FDA. Unlike previous medication studies that have sought to pharmacologically reduce cocaine reinforcement, seeking or craving, this exploratory clinical trial will test d-cycloserine (DCS) for its ability to improve learning-based behavioral treatment of cocaine dependence. DCS is an NMDA partial agonist that has been shown to robustly improve learning in preclinical models, including extinction of cocaine conditioned place preference and blockade of cocaine reacquisition, and to improve extinction-learning based exposure therapy for multiple anxiety disorders. This Phase II clinical trial will investigate the pharmacological (DCS) enhancement of a behavioral treatment combining contingency management (CM) and novel home-environment exposure therapy sessions for cocaine dependence. High magnitude CM incentives will be used to promote the cocaine abstinence necessary for extinction in home-based exposure sessions. Participants will be randomized into 2 groups: 1. CM with placebo (CM+PL), and 2. CM with DCS (CM+DCS). For 19 days after group assignment, participants will report to the laboratory 3 times per week (Mon, Wed, Fri) to provide urine samples, receive contingent vouchers, and complete assessments of drug use, craving, mood, withdrawal, and quit self-efficacy. DCS (50 mg) or placebo will be administered on Mon, Wed and Fri study visits (at the end of the lab visit before returning to the home environment for exposure sessions during the time of DCS action). Follow-up visits will be conducted at 1 week, 1 month, and 3 months post-CM completion, during which time measures of drug use (self-reported and urinalysis), craving, mood, and withdrawal will be obtained. Comparison of continuous abstinence post-CM between the groups will be the primary outcome measure. During an initial laboratory session, a battery of learning/cognitive tasks will test for forms of learning/cognition enhanced by DCS that might contribute to the treatment effect. This project will test the efficacy of a novel intervention for cocaine dependence that was developed based on a known efficacious cocaine dependence treatment (CM), principles of extinction learning theory, and a medication shown to improve preclinical learning in general, including extinction of cocaine conditioning, and clinical learning-based exposure treatment of anxiety disorders. The study may indicate cost effective additions (home exposure sessions and DCS) to extend CM benefit after the removal of contingencies, and therefore may increase the dissemination of CM in community settings.

Study Design

• Study Type: Interventional
• Actual Enrollment: 52 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Improving Learning-based Treatment of Cocaine Dependence With Medication
• Study Start Date: Sep 1, 2011
• Actual Primary Completion Date: Mar 1, 2013
• Actual Study Completion Date: Mar 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 50 mg d-cycloserine active drug condition	Drug: d-cycloserine; 50 mg d-cycloserine
Placebo Comparator: Sugar pill Inactive placebo	Drug: sugar pill; placebo

Outcome Measures

Primary Outcome Measures

1. Urinalysis Benzoylecgonine (Cocaine Metabolite)(ng/ml) [1 month post-treatment]

   The primary outcome for this study will be post-treatment continuous abstinence, as assessed by urinalysis results

2. Medication Side-effects [1 month post-treatment.]

   self-report of medication side effects (Units of Measure is the count of specific reported effects)

Secondary Outcome Measures

1. Learning Task by Itami and Uno [At the baseline laboratory visit]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 60 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

• 18-60 years of age (> 60 due to age-related effects on cognitive functioning)

• Satisfy DSM-IV criteria for cocaine dependence (primarily crack)

• Able to complete all study measures

• Currently seeking treatment for cocaine dependence

Exclusion Criteria:

• Meets DSM-IV criteria for dependence on a drug other than cocaine or nicotine (may meet abuse criteria for other drugs)

• Pregnant, breast feeding, or planning to become pregnant within 3 months

• If female, do not agree to use an effective means of birth control during the course of treatment (via phone screen)

• History of seizure disorder, severe hepatic impairment, porphyria, serious head trauma, dementia, or significant cognitive impairment

• Diagnosis of current major psychiatric disorder besides substance dependence or abuse

• Reported use of DCS in the past year

• Illiteracy, as will be determined during in-person screening

• Concurrently prescribed or using ethionamide or isoniazid (both used to treat tuberculosis)

• Positive urine result for opioids at screening interview

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Behavioral Pharmacology Research Unit	Baltimore	Maryland	United States	212124

Sponsors and Collaborators

• Johns Hopkins University
• National Institute on Drug Abuse (NIDA)

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Matthew Johnson, Assistant Professor, Johns Hopkins University
• ClinicalTrials.gov Identifier: NCT01526538
• Other Study ID Numbers: R21DA029823
• First Posted: Feb 6, 2012
• Last Update Posted: Feb 15, 2017
• Last Verified: Dec 1, 2016

• Additional relevant MeSH terms: Cocaine-Related Disorders; Cycloserine

Study Results

Participant Flow

Arm/Group Title	50 mg D-cycloserine	Sugar Pill
Arm/Group Description	active drug condition d-cycloserine: 50 mg d-cycloserine	Inactive placebo sugar pill: placebo
Period Title: Overall Study
STARTED	30	22
COMPLETED	21	18
NOT COMPLETED	9	4

Baseline Characteristics

Arm/Group Title	50 mg D-cycloserine	Sugar Pill	Total
Arm/Group Description	active drug condition d-cycloserine: 50 mg d-cycloserine	Inactive placebo sugar pill: placebo	Total of all reporting groups
Overall Participants	21	18	39
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	51.3 (5.3)	52.1 (4.9)	51.7 (5.1)
Gender (Count of Participants)
Female	6 28.6%	6 33.3%	12 30.8%
Male	15 71.4%	12 66.7%	27 69.2%

Outcome Measures

1. Primary Outcome

Title	Urinalysis Benzoylecgonine (Cocaine Metabolite)(ng/ml)
Description	The primary outcome for this study will be post-treatment continuous abstinence, as assessed by urinalysis results
Time Frame	1 month post-treatment

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	50 mg D-cycloserine	Sugar Pill
Arm/Group Description	active drug condition d-cycloserine: 50 mg d-cycloserine	Inactive placebo sugar pill: placebo
Measure Participants	22	18
Mean (Standard Deviation) [ng/ml]	36.7 (7.7)	32.4 (6.6)

2. Primary Outcome

Title	Medication Side-effects
Description	self-report of medication side effects (Units of Measure is the count of specific reported effects)
Time Frame	1 month post-treatment.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	D-cycloserine	Control
Arm/Group Description	Study medication under investigation	Placebo (sugar pill)
Measure Participants	21	18
Number [Adverse event reports]	0	0

3. Secondary Outcome

Title	Learning Task by Itami and Uno
Time Frame	At the baseline laboratory visit

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	50 mg D-cycloserine	Sugar Pill
Arm/Group Description	active drug condition d-cycloserine: 50 mg d-cycloserine	Inactive placebo sugar pill: placebo
Measure Participants	21	18
Mean (Standard Error) [% correct]	81.5 (3.5)	72.9 (4.4)

Adverse Events

Time Frame	2 years
Arm/Group Title	50 mg D-cycloserine		Sugar Pill
Arm/Group Description	active drug condition d-cycloserine: 50 mg d-cycloserine		Inactive placebo sugar pill: placebo
All Cause Mortality
	50 mg D-cycloserine		Sugar Pill
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	50 mg D-cycloserine		Sugar Pill
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/21 (0%)		0/18 (0%)
Other (Not Including Serious) Adverse Events
	50 mg D-cycloserine		Sugar Pill
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/21 (0%)		0/18 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.