Efficacy and Safety of Sustained-release Dexamphetamine in Patients With Moderate to Severe Cocaine Use Disorder
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Простыми словами
Автоматическая сводка по структурированным данным реестра. Она помогает сориентироваться, но не заменяет официальный протокол или оценку врача.
- Что изучают
- В протоколе указаны: Sustained-release Dexamphetamine, Placebo.
- Кому может быть актуально
- Состояния в реестре: Cocaine Use Disorder. Базовые параметры: от 18 лет · Все.
- Что важно проверить
- Возраст, диагноз и пол — только базовые ориентиры. Предыдущее лечение, анализы и другие обязательные условия указаны ниже в критериях участия.
- Где проводится
- Нидерланды
- Следующий шаг
- Сохраните исследование, покажите его лечащему врачу и уточните актуальный статус у исследовательского центра. Расходы, документы и поездка →
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Официальное название
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
Обзор
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.
Подробное описание
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.
OUTCOME PARAMETERS: Primary endpoint: number of days of cocaine abstinence in the final 4 weeks of treatment, assessed by combined self-report and urinalysis. Key secondary endpoint: Good or improved overall health status (in terms of physical and mental health, and social functioning).
SAMPLE SIZE/DATA-ANALYSIS: Assuming 5 days difference in cocaine abstinent days in the final 4 weeks of the study to be clinically relevant requires 102 patients per treatment group in order to detect these 5 days difference (pooled standard deviation: 11 days; two-sided alpha=0.05; power=0.90). Primary analysis: As cocaine abstinence is assessed throughout the trial, the numbers of days of cocaine abstinence in the sequential 4 week periods will be treated as repeated measure. The primary analysis will be a likelihood-based mixed model of repeated measures (MMRM) approach, including treatment, fixed timepoints (periods of 4 weeks, categorical) and their interaction as fixed factors and subject as random effect. Treatment center and overall health status (both stratification factors) will be included as covariates. The contrast between the two groups at week 24 will be the primary comparison.
Вмешательства
- Препарат Sustained-release Dexamphetamine
During the first week, patients will be individually titrated to the target dose of 90 mg/day, if tolerated. From the second week onwards, patients are prescribed 3 tablets (30 mg) per day, if tolerated. Titration can be slower but should be finished at the end of week 4. After 4 weeks dosages can no longer be increased, and only be reduced. Patients will visit the treatment centre 2 times per week to take their study medication under supervision of the treatment staff and to receive take-home - Препарат Placebo
Dispensed under the same conditions and with similar frequency as the investigational product (see above). After 24 weeks study medication will be discontinued in the placebo group.
Первичные конечные точки
- 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. [Срок оценки: Final 4 weeks of treatment (first study phase; i.e., week 21-24)]
Вторичные конечные точки (12)
- 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). [Срок оценки: 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. [Срок оценки: 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. [Срок оценки: 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. [Срок оценки: 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. [Срок оценки: 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. [Срок оценки: 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. [Срок оценки: 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. [Срок оценки: During 24 weeks treatment]
- Secondary outcome measures for the primary study objective: Cocaine use related endpoints: (8) Cocaine craving. [Срок оценки: 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. [Срок оценки: 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. [Срок оценки: 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. [Срок оценки: Final 4 weeks of treatment discontinuation phase (second study phase; i.e., week 27-30)]
Критерии участия
Критерии включения
- 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.
Критерии исключения
- 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.
Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.
Здоровые добровольцы: Нет
Дизайн исследования
- Распределение
- Рандомизированное
- Модель
- Параллельные группы
- Маскирование
- Четверное слепое
- Основная цель
- Лечение
Центры проведения
Нидерланды · 1 центр
- Brijder Den Haag — The Hague
Публикации
- Nuijten M, Blanken P, van de Wetering B, Nuijen B, van den Brink W, Hendriks VM. Sustained-release dexamfetamine in the treatment of chronic cocaine-dependent patients on heroin-assisted treatment: a randomised, double-blind, placebo-controlled trial. Lancet. 2016 May 28;387(10034):2226-34. doi: 10.1016/S0140-6736(16)00205-1. Epub 2016 Mar 22. PMID 27015909
- Blanken P, Nuijten M, van den Brink W, Hendriks VM. Clinical effects beyond cocaine use of sustained-release dexamphetamine for the treatment of cocaine dependent patients with comorbid opioid dependence: secondary analysis of a double-blind, placebo-controlled randomized trial. Addiction. 2020 May;115(5):917-923. doi: 10.1111/add.14874. Epub 2020 Jan 6. PMID 31908066
Идентификаторы
NCT: NCT05529927 · 10140262110025