D-Serine for Cocaine Dependence Pilot

NCT01715051 | Withdrawn Phase 2

• 1 other identifier: TW-116541
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

The primary objective of this study is to collect pilot data on the efficacy of D-serine, relative to placebo, as a cocaine dependence treatment. Secondary objectives include evaluating D-serine, relative to placebo, on: 1. safety in treating cocaine-dependent adults and 2. tolerability.

Conditions

Cocaine Dependence

Keywords

cocaine; D-serine; Drug dependence

Outcome Measures

Primary Outcomes (1)

• Proportion of participants with cocaine abstinence for three or more consecutive weeks as assessed by self-report and urine BE

  The Timeline Follow-back (TLFB) procedure will be used to assess the participants' self-reported use of substances for each day of the study. Urine samples will be collected at each study visit using temperature monitoring and the validity of urine samples will be checked with the use of a commercially available adulterant test. The urine samples will be sent to a laboratory for analysis. The self-report and urine BE results will be combined to score each participant as cocaine abstinent or non-abstinent for each study week.

  Week 13 visit

Secondary Outcomes (5)

• Proportion of cocaine-negative Urine Drug Screens (UDS) during the treatment phase

  Week 13 visit

• Proportion of participants achieving cocaine abstinence during study weeks 11 and 12

  Week 11 and Week 12

• Number of participants with nephrotoxic effects as measured by urinalysis

  Study week 13

• Change from baseline in liver function at 6 weeks

  Baseline and Week 6

• Change from baseline in liver function at Week 12

  Baseline and Week 12

Study Arms (2)

D-serine

ACTIVE COMPARATOR

Participants randomized to D-serine will receive 500 mg tablets of D-serine based on the participant's weight in addition to weekly cognitive behavioral therapy (CBT). The number of capsules prescribed will be based on the target \~60 mg/kg per day dose. In practice, the mg/kg daily dose will range between approximately 55 mg/kg and 65 mg/kg. Dosing will be bid.

Drug: D-serine; Behavioral: Cognitive Behavioral Therapy

Placebo

PLACEBO COMPARATOR

The number of placebo capsules prescribed to a study participant per day will be based on the participant's weight and will be bid dosing to match the dosing of D-serine.

Behavioral: Cognitive Behavioral Therapy; Drug: Placebo

Interventions

D-serine DRUG

The molecular formula for D-serine is C3H7NO3. D-serine is being used in IND# 71,369 (D Javitt, PI) and in IND#76,940 (H Singer, PI). This approved D-serine will be purchased by the Research Pharmacy at Johns Hopkins and will be encapsulated into capsules containing 500 mg of D-serine.

D-serine

Cognitive Behavioral Therapy BEHAVIORAL

CBT sessions will be offered weekly to both active medication and placebo arms. The National Institute on Drug Abuse (NIDA) published CBT treatment manual for cocaine dependence, written by Kathleen Carroll, Ph.D., will be utilized. The skills taught in this CBT manual include (1) self-monitoring and functional analysis of situational factors associated with craving or drug use; (2) learning alternative non-drug responses for handling high risk situations; and (3) general lifestyle modifications (e.g., increasing pleasant drug-free events, anger management, interpersonal skills, general problem-solving).

D-serine; Placebo

Placebo DRUG

The Research Pharmacy at Johns Hopkins will produce matching placebo capsules.

Also known as: Sugar Pill

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• be 18 years of age or older
• be able to understand the study, and having understood, provide written informed consent in English
• meet DSM-IV-TR diagnostic criteria for current (within the last 12 months) dependence for cocaine,
• have at least 1 positive urine BE specimen (\> 300 ng/mL) during screening/baseline with a minimum of 3 urine samples tested if screening/baseline is completed within 7 days or a minimum of 4 urine samples tested if screening/baseline is completed during a period \>7 days and ≤ 14 days
• have a willingness to comply with all study procedures and medication instructions
• be seeking treatment for cocaine dependence
• weigh \>101 and \<340 pounds
• if female and of child bearing potential, agree to use one of the following methods of birth control:
• oral contraceptives
• contraceptive patch
• barrier (diaphragm or condom)
• intrauterine contraceptive system
• levonorgestrel implant
• medroxyprogesterone acetate contraceptive injection
• complete abstinence from sexual intercourse

You may not qualify if:

• have current dependence, defined by DSM-IV-TR criteria, on any psychoactive substance other than cocaine, alcohol, nicotine, or marijuana or physiological dependence on alcohol requiring medical detoxification.
• have been enrolled in a medication assisted treatment program for opioid dependence (e.g., methadone, buprenorphine) within 2 months of consent.
• have a medical or psychiatric condition that, in the judgment of the study physician, would make study participation unsafe or which would make treatment compliance difficult. Medical conditions that may compromise participant safety or study conduct include, but are not limited to:
• significant renal disease or estimated Glomerular Filtration Rate (GFR) ≤ 60
• AIDS according to the current Centers for Disease Control (CDC) criteria for AIDS
• liver function tests greater than 3 times the upper limit of normal
• serum creatinine outside the normal range
• have initiated or had a dose change in psychotropic medication in the 28 days prior to randomization if currently taking psychotropic medication
• have a known or suspected hypersensitivity to D-serine
• be pregnant or breastfeeding or plan to become pregnant
• plan to take any of the following agents during the treatment phase:
• nonsteroidal anti-inflammatory drugs (NSAIDs)
• angiotensin-converting enzyme (ACE) inhibitors
• aminoglycosides
• angiotensin receptor blockers (ARBs)

Sponsors & Collaborators

• Theresa Winhusen: lead

Study Sites (1)

Maryhaven, Inc

Columbus, Ohio, 43207, United States

Location

Related Publications (3)

• Botreau F, Paolone G, Stewart J. d-Cycloserine facilitates extinction of a cocaine-induced conditioned place preference. Behav Brain Res. 2006 Sep 15;172(1):173-8. doi: 10.1016/j.bbr.2006.05.012. Epub 2006 Jun 12.

  PMID: 16769132 BACKGROUND

• Paolone G, Botreau F, Stewart J. The facilitative effects of D-cycloserine on extinction of a cocaine-induced conditioned place preference can be long lasting and resistant to reinstatement. Psychopharmacology (Berl). 2009 Jan;202(1-3):403-9. doi: 10.1007/s00213-008-1280-y. Epub 2008 Aug 10.

  PMID: 18695929 BACKGROUND

• Thanos PK, Bermeo C, Wang GJ, Volkow ND. D-cycloserine accelerates the extinction of cocaine-induced conditioned place preference in C57bL/c mice. Behav Brain Res. 2009 May 16;199(2):345-9. doi: 10.1016/j.bbr.2008.12.025. Epub 2008 Dec 30.

  PMID: 19152811 BACKGROUND

MeSH Terms

Conditions

Cocaine-Related Disorders; Substance-Related Disorders

Interventions

Cognitive Behavioral Therapy; Sugars

Condition Hierarchy (Ancestors)

Chemically-Induced Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Behavior Therapy; Psychotherapy; Behavioral Disciplines and Activities; Carbohydrates

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: October 9, 2012
• First Posted: October 26, 2012
• Study Start: February 1, 2014
• Primary Completion: September 1, 2019
• Study Completion: September 1, 2019
• Last Updated: February 6, 2014

Record last verified: 2014-02

Locations

US (1)