A Double-Blind, Placebo-Controlled Pilot Study to Evaluate the Safety, Tolerability, and Efficacy of D-Serine for Cocaine Dependence
试验速览
- 阶段
- 2 期
- 状态
- 撤回
- 发起方
- 试验地点
- 1
- 主要终点
- Proportion of participants with cocaine abstinence for three or more consecutive weeks as assessed by self-report and urine BE
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Care Provider, Investigator)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
- •hormonal vaginal contraceptive ring
排除标准
- •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)
- •calcineurin inhibitors
- •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.)
- •be a significant suicidal/homicidal risk
研究组 & 干预措施
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.
干预措施: D-serine (Drug)
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.
干预措施: Cognitive Behavioral Therapy (Behavioral)
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.
干预措施: Cognitive Behavioral Therapy (Behavioral)
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.
干预措施: Placebo (Drug)
结局指标
主要结局
Proportion of participants with cocaine abstinence for three or more consecutive weeks as assessed by self-report and urine BE
时间窗: Week 13 visit
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.
次要结局
- Change from baseline in liver function at 6 weeks(Baseline and Week 6)
- Proportion of participants achieving cocaine abstinence during study weeks 11 and 12(Week 11 and Week 12)
- Change from baseline in liver function at Week 12(Baseline and Week 12)
- Proportion of cocaine-negative Urine Drug Screens (UDS) during the treatment phase(Week 13 visit)
- Number of participants with nephrotoxic effects as measured by urinalysis(Study week 13)
研究者
Theresa Winhusen
Associate Professor
University of Cincinnati