Clinical trial NCT01715051: D-Serine for Cocaine Dependence Pilot
Official title: A Double-Blind, Placebo-Controlled Pilot Study to Evaluate the Safety, Tolerability, and Efficacy of D-Serine for Cocaine Dependence
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE2
Conditions: Cocaine Dependence
Keywords: cocaine
D-serine
Drug dependence
Lead sponsor: University of Cincinnati
Sponsor class: OTHER
First posted: 2012-10-26
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Detailed description: STUDY DESIGN. This is a 12 week, 2 group randomized controlled trial that will be completed in an outpatient setting. Eligible participants will be randomized to D-serine or matching placebo and will be scheduled to attend three research visits per week throughout the active treatment phase which begins with randomization and ends on day 7 of study week 12. A single visit will be scheduled in week 13 to complete retrospective data for week 12. Participants will receive D-serine or placebo throughout the 12-week active treatment phase. Randomization will be in a 1:1 ratio, stratified by cocaine use frequency (\<10 days or ≥ 10 days in the 28 days prior to consent).

STUDY POPULATION. Approximately 80 participants recruited from a single site will be randomized. The study population will include adults who meet Diagnostic and Statistical Manual-IV-Text Revision (DSM-IV-TR) criteria for cocaine dependence who have used cocaine in the 30 days prior to consent and who provide at least one benzoylecgonine (BE) positive urine during screening/baseline.

TREATMENTS. Study participants will be randomly assigned to receive either D-serine (target \~60 mg/kg per day) or matching placebo. All participants will receive once weekly manual-guided cognitive behavioral therapy during the 12 week treatment period. Medication adherence will be assessed with the Medication Events Monitoring System (MEMS).

EFFICACY ASSESSMENTS. The primary outcome measure will be cocaine abstinence for three or more consecutive weeks, with abstinence during a week defined as self-report of no cocaine use during the week as well as negative urine BE (BE\<300 ng/mL) results during the week with at least two urine samples provided. Key secondary efficacy measures include the proportion of urine BE negative results obtained and cocaine abstinence during study weeks 11 and 12 as measured by self-report and urine BE. Other efficacy measures include drug attention bias, cocaine craving, drug compulsivity, cocaine withdrawal symptoms, and treatment retention.

SAFETY ASSESSMENTS. Safety measures include urinalysis, adverse events (AEs), vitals, electrocardiogram (ECG), and laboratory tests. Tolerability will be assessed by the proportion of participants needing a dose reduction and being discontinued from study medication.

ANALYSIS. Each outcome variable will be analyzed using appropriate statistical methods for the intention-to-treat (ITT) population and the evaluable population. All participants who have taken at least one study medication dose will be included in the safety analysis. Data will be summarized by treatment group. Summary statistics will include the mean, sample size, standard deviation, median, minimum and maximum values for continuous variables, and frequencies and percentages for categorical variables.

Eligibility criteria: Inclusion Criteria:

1. be 18 years of age or older
2. be able to understand the study, and having understood, provide written informed consent in English
3. meet DSM-IV-TR diagnostic criteria for current (within the last 12 months) dependence for cocaine,
4. 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
5. have a willingness to comply with all study procedures and medication instructions
6. be seeking treatment for cocaine dependence
7. weigh \>101 and \<340 pounds
8. 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
   * hormonal vaginal contraceptive ring

Exclusion Criteria:

1. 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.
2. have been enrolled in a medication assisted treatment program for opioid dependence (e.g., methadone, buprenorphine) within 2 months of consent.
3. 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
4. have initiated or had a dose change in psychotropic medication in the 28 days prior to randomization if currently taking psychotropic medication
5. have a known or suspected hypersensitivity to D-serine
6. be pregnant or breastfeeding or plan to become pregnant
7. 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)
   * calcineurin inhibitors
8. be anyone who, in the judgment of the investigator, would not be expected to complete the study protocol (e.g., due to relocation from the clinic area, probable incarceration, etc.)
9. be a significant suicidal/homicidal risk

Primary outcomes:
measure: Proportion of participants with cocaine abstinence for three or more consecutive weeks as assessed by self-report and urine BE
timeFrame: Week 13 visit
Secondary outcomes:
measure: Proportion of cocaine-negative Urine Drug Screens (UDS) during the treatment phase
timeFrame: Week 13 visit
measure: Proportion of participants achieving cocaine abstinence during study weeks 11 and 12
timeFrame: Week 11 and Week 12
measure: Number of participants with nephrotoxic effects as measured by urinalysis
timeFrame: Study week 13
measure: Change from baseline in liver function at 6 weeks
timeFrame: Baseline and Week 6
measure: Change from baseline in liver function at Week 12
timeFrame: Baseline and Week 12
Other outcomes:
Locations:
city: Columbus
country: United States
facility: Maryhaven, Inc
state: Ohio
Study officials:
References:
citation: 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.
citation: 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.
citation: 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.