Efficacy and Safety of 24 Weeks Sustained-release Dexamphetamine in Patients With Moderate to Severe Cocaine Use Disorder With Comorbid Opioid Use Disorder - A Multicenter Randomized, Double-blind, Placebo-controlled Study
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 204
- 试验地点
- 1
- 主要终点
- Primary outcome measure for the primary study objective (to evaluate the efficacy of 24 weeks SR-dexamphetamine, compared with 24 weeks placebo): the number of days cocaine abstinence.
研究概览
简要总结
In The Netherlands, each year, about 15 thousand people come into treatment because of problems with cocaine use. There is no approved medication for treatment of cocaine addiction and the psychosocial treatment patients receive is not successful for everyone; many return to treatment several times. There is evidence that agonist ("replacement") medications are effective in treating addiction: methadone for heroin addiction; nicotine replacement for smokers. Dexamphetamine is a stimulant medication registered for treatment of ADHD. It may also be effective as agonist treatment for people with cocaine addiction.
It will be investigated whether sustained-release dexamphetamine in people with cocaine addiction, participating in routine methadone maintenance treatment for their comorbid opioid use disorder, (1) reduces cocaine use and (2) improves their health and quality of life.
详细描述
RESEARCH QUESTION/RATIONALE: Treatment for patients with cocaine use disorder is modestly effective and there is an urgent need for more effective treatments. Several randomized controlled trials, including our previous proof of principle study (Nuijten et al., 2016, The Lancet), suggest that sustained-release dexamphetamine is the most promising medication for the treatment of cocaine use disorder.
HYPOTHESIS & OBJECTIVES: Therefore, it is hypothesized that sustained-release dexamphetamine is effective in patients with cocaine use disorder in terms of reducing cocaine use and improving health and quality of life.
STUDY DESIGN: Multicentre randomized, double-blind, placebo-controlled study in 204 patients with cocaine use disorder - participating in routine methadone maintenance treatment for their comorbid opioid use disorder. In the 1st study phase (24 weeks) the efficacy and safety of sustained-release dexamphetamine is compared with placebo. In the 2nd double-blind, placebo-controlled randomized treatment discontinuation phase (6 weeks), we assess the consequences of discontinuation of sustained-release dexamphetamine treatment.
STUDY POPULATION: Patients with moderate/severe cocaine use disorder participating in routine oral methadone maintenance treatment for their comorbid opioid use disorder .
INTERVENTION: The investigational product is in tablets, containing 30 mg dexamphetamine sulphate in sustained-release formulation. Patients will be titrated to the target dose of 90 mg/day, if tolerated. Medication is dispensed twice weekly.
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •male and female patients between 18 years and over;
- •actively participating in opioid agonist treatment with oral methadone;
- •with moderate or severe cocaine use disorder according to DSM-5;
- •with regular use of cocaine in the previous month (i.e., ≥8 days/month);
- •with snorting, inhaling or injecting cocaine use as primary route of administration;
- •express the intention to reduce or stop their cocaine use;
- •be able and willing to attend the treatment center for 2 days per week;
- •be able and willing to co-operate with the required study assessments and study procedures; and
- •have provided written informed consent.
排除标准
- •severe medical (e.g., severe renal or hepatic insufficiency/failure) or severe psychiatric problems (e.g. previous or acute severe psychotic episode, acute suicidality, current bipolar disorder);
- •cardiovascular problems: clinically relevant ECG abnormalities suggestive of channelopathy or structural or ischemic heart disease, or a prolonged QTc interval (≥500 msec); moderate to severe hypertension (i.e., SBP>140; DBP>90); HR>100, known coronary artery disease (i.e., angina pectoris, acute myocardiac infarction), known cardiomyopathy, CVA;
- •glaucoma;
- •Gilles-de-la-Tourette syndrome;
- •pheochromocytoma;
- •hyperthyroid status;
- •pregnancy or continued lactation;
- •use of monoamine oxidase inhibitor(s) (MAOI): currently or in the past 14 days;
- •treatment with other prescription psychostimulants that might potentially be effective for stimulant use disorder (i.e., (immediate release) dexamphetamine, lisdexamphetamine, methylphenidate, or modafinil);
- •anticipated need for inpatient treatment (clinical judgement);
- •(expected) inability to complete the 30 weeks study (e.g., planned holidays, expected incarceration or hospitalization);
- •insufficient command of the Dutch language; and
- •current participation in another addiction treatment study.
研究组 & 干预措施
Placebo
Identical matched placebo, dispensed under the same conditions and with similar frequency as the investigational product (see above).
干预措施: Placebo (Drug)
Sustained-release Dexamphetamine
Tablets of 30 mg sustained-release dexamphetamine sulphate. Target dose: 90 mg/day, if tolerated. Tablets have to be taken daily, in the morning, per os for 24 weeks.
干预措施: Sustained-release Dexamphetamine (Drug)
结局指标
主要结局
Primary outcome measure for the primary study objective (to evaluate the efficacy of 24 weeks SR-dexamphetamine, compared with 24 weeks placebo): the number of days cocaine abstinence.
时间窗: Final 4 weeks of treatment (first study phase; i.e., week 21-24)
The number of days of cocaine abstinence in the final 4 weeks of treatment, assessed by combined self-report and urinalysis.
次要结局
- Key secondary outcome measure for the primary study objective ("good or improved overall health status", in terms of physical health, mental health, and social functioning).(Final 4 weeks of treatment (i.e. week 21 - week 24) compared with baseline)
- Secondary outcome measures for the primary study objective: Cocaine use related secondary endpoints: (1) Total number of days cocaine abstinence.(During first 12 weeks treatment (i.e., 0-84 days))
- Secondary outcome measures for the primary study objective: Cocaine use related secondary endpoints: (2) Total number of days cocaine abstinence.(During 24 weeks treatment (i.e., 0-168 days))
- Secondary outcome measures for the primary study objective: Cocaine use related secondary endpoints: (3) Complete abstinence from cocaine.(During 24 weeks treatment)
- Secondary outcome measures for the primary study objective: Cocaine use related endpoints: (4) Achieving a period of sustained abstinence from cocaine for at least 21 consecutive days.(During 24 weeks treatment)
- Secondary outcome measures for the primary study objective: Cocaine use related endpoints: (5) At least 40% reduction in cocaine use (days/month) in the final 4 weeks of treatment (weeks 21-24), compared with baseline.(The final 4 weeks of treatment (weeks 21-24))
- Secondary outcome measures for the primary study objective: Cocaine use related endpoints: (6) Number of weeks of uninterrupted cocaine abstinence sustained till abstinence during final treatment week in study phase 1.(Final treatment week in study phase 1)
- Secondary outcome measures for the primary study objective: Cocaine use related endpoints: (7) Average number of cocaine administrations on days that cocaine was used.(During 24 weeks treatment)
- Secondary outcome measures for the primary study objective: Cocaine use related endpoints: (8) Cocaine craving.(During 24 weeks treatment)
- Secondary outcome measure for the secondary study objective (to assess the acceptance, tolerability, and safety of 24 weeks SR-dexamphetamine): treatment completion; medication adherence; adverse events, and serious adverse events.(The first 24 weeks of treatment)
- Secondary outcome measure for the secondary study objective (to evaluate the effect of discontinuation of SR-dexamphetamine after 24 weeks treatment): days cocaine abstinence.(Final 4 weeks of treatment discontinuation phase (second study phase; i.e., week 27-30))
- Secondary outcome measure for the secondary study objective (to evaluate the effect of discontinuation of SR-dexamphetamine after 24 weeks treatment): overall health status.(Final 4 weeks of treatment discontinuation phase (second study phase; i.e., week 27-30))
- Secondary outcome measure for the secondary study objective (to evaluate the effect of discontinuation of SR-dexamphetamine after 24 weeks treatment): dichotomous outcome of deterioration.(Final 4 weeks of treatment discontinuation phase (second study phase; i.e., week 27-30))
研究者
Vincent Hendriks
Professor
Parnassia Addiction Research Centre