D-Serine for Cocaine Dependence Pilot (STED-CD)
Behavioral: Cognitive Behavioral Therapy
|Study Design:||Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
|Official Title:||A Double-Blind, Placebo-Controlled Pilot Study to Evaluate the Safety, Tolerability, and Efficacy of D-Serine for Cocaine Dependence|
- Proportion of participants with cocaine abstinence for three or more consecutive weeks as assessed by self-report and urine BE [ Time Frame: Week 13 visit ] [ Designated as safety issue: No ]
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.
- Proportion of cocaine-negative Urine Drug Screens (UDS) during the treatment phase [ Time Frame: Week 13 visit ] [ Designated as safety issue: No ]The proportion of cocaine-negative UDS results is calculated by the number of results negative for cocaine (BE<300 ng/mL) divided by the total number of UDS results obtained for the participant during the 12 week treatment phase.
- Proportion of participants achieving cocaine abstinence during study weeks 11 and 12 [ Time Frame: Week 11 and Week 12 ] [ Designated as safety issue: No ]To be scored as abstinent for the last two weeks of treatment, a participant must provide: 1. 14 days of self-reported use for weeks 11 and 12 with no self-reported cocaine use and 2. provide at least 2 urine samples per week for study weeks 11 and 12 with all urine results negative for BE (BE<300 ng/mL). Any participant failing to meet these criteria will be scored as not abstinent. At a group level, this outcome translates into the proportion of participants in each treatment arm who are cocaine abstinent during the last two weeks of treatment.
- Number of participants with nephrotoxic effects as measured by urinalysis [ Time Frame: Study week 13 ] [ Designated as safety issue: Yes ]Because this is the first outpatient study of D-serine being conducted for cocaine dependence and because cocaine can be nephrotoxic, possible nephrotoxic effects will be monitored carefully by completing microscopic urinalysis on a weekly basis.
- Change from baseline in liver function at 6 weeks [ Time Frame: Baseline and Week 6 ] [ Designated as safety issue: Yes ]Quantitative analysis of participant blood samples will be performed to measure liver function. Liver function will be determined by analysis of the following:creatinine, alanine aminotransferase (ALT/SGPT), aspartate aminotransferase (AST/SGOT), gamma glutamyltranspeptidase (GGT), and blood urea nitrogen (BUN).
- Change from baseline in liver function at Week 12 [ Time Frame: Baseline and Week 12 ] [ Designated as safety issue: Yes ]Quantitative analysis of participant blood samples will be performed to measure liver function. Liver function will be determined by analysis of the following:creatinine, alanine aminotransferase (ALT/SGPT), aspartate aminotransferase (AST/SGOT), gamma glutamyltranspeptidase (GGT), and blood urea nitrogen (BUN).
|Study Start Date:||February 2014|
|Estimated Study Completion Date:||September 2019|
|Estimated Primary Completion Date:||September 2019 (Final data collection date for primary outcome measure)|
Active Comparator: D-serine
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.
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.Behavioral: Cognitive Behavioral Therapy
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).
Placebo Comparator: Placebo
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
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).Drug: Placebo
The Research Pharmacy at Johns Hopkins will produce matching placebo capsules.
Other Name: Sugar Pill
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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01715051
|United States, Ohio|
|Columbus, Ohio, United States, 43207|