Adjunctive Cannabidiol for Recovery From Opioid Study (ACROS)
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 入组人数
- 450
- 试验地点
- 2
- 主要终点
- Percentage of study participants with negative urine toxicology for illicit opioid use
研究概览
简要总结
The long-term goal of the project is to determine whether cannabidiol (CBD) can reduce craving and relapse in individuals with opioid use disorder (OUD). The first phase of this project was an open cross-over design study in healthy individuals to confirm the safety and pharmacokinetic (PK) effects of CBD (BSPG CBD; Brains Bioceutical). The second phase was a double-blinded randomized controlled trial to determine whether CBD reduces craving and anxiety in individuals with OUD maintained on opioid agonist therapy. This phase 3 trial will determine whether CBD can serve as a potential adjunct treatment to reduce illicit opioid use in individuals with OUD maintained on opioid agonist therapy.
详细描述
Responding to the urgent calls for developing non-opioid therapeutics to address the opioid addiction epidemic, we have been investigating the therapeutic potential of cannabidiol (CBD), a non-intoxicating cannabinoid as a possible strategy. Our preclinical animal studies demonstrated that CBD decreases cue-induced heroin seeking behavior during drug abstinence, associated with the incubation of craving. Moreover, the effects of CBD to reduce heroin-seeking behavior was still evident even in animals that were maintained on methadone. We also showed in randomized, double-blind placebo- controlled design human clinical trials that acute CBD (Epidiolex) administration (400 mg and 800mg) decreased craving and anxiety associated with heroin cues in abstinent individuals with heroin use disorder, an effect that persisted even a week after the last CBD dose (given daily for 3 days). Moreover, another of our human studies showed that CBD was safe even in combination with a potent opioid agonist (fentanyl) to address a potential relapse condition suggesting negligible negative interaction with opioids. Building on those studies, we next set out to investigate the potential for CBD as an adjunctive treatment to methadone or buprenorphine in opioid use disorder (OUD). To that end, we first conducted Phase 1 pharmacokinetic studies with a CBD formulation in oral capsules (BSPG CBD; Brains Bioceutical) in healthy participants that showed that oral administration of BSPG CBD (400 mg) led to comparable pharmacokinetic parameters of the CBD plasma levels and its active metabolite as Epidiolex (400 mg), an FDA-approved comparator CBD product that previously reduced craving. In the Phase 2 clinical trial, we evaluated the effect of 200mg CBD (vs placebo) twice daily for 4 weeks and an additional 4 weeks of 400 mg CBD, twice daily, on cue-induced craving and anxiety in individuals with OUD who are maintained on methadone or buprenorphine. In the next phase of this IND application, we will extend the Phase 2 study to evaluate the effects of 200mg CBD, 400 mg CBD and placebo, taken twice daily, over a 24-week period in the OUD individuals maintained on methadone or buprenorphine. Our goals in this double-blinded randomized controlled clinical trial (RCT) are to investigate the potential of CBD to 1) decrease illicit opioid use and 2) reduce craving.
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)
盲法说明
Investigators and participants will be blinded to treatment assignment. The staff involved in primary outcome assessment and laboratory tests in local laboratories will also be blinded to treatment assignment. Randomization will be generated centrally and performed through a Web-based data collection system that automates the delivery of the randomization codes. The treatment assignment will be sent to the unblinded pharmacist or unblinded study team electronically, in a secure fashion, and electronic verification of the treatment assignment will be required before proceeding with the treatment intervention. Active drug and placebo will be identical to maintain study blinding.
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
- •Individuals between 18 and 65 years old.
- •Ability to understand and give informed consent.
- •Current opioid use disorder (OUD) or OUD in remission while on maintenance therapy with OAT, as determined by DSM-5 with the M.I.N.I. interview (Mini-International Neuropsychiatric Interview).
- •Current opioid agonist maintenance treatment with methadone or buprenorphine for at least 14 days prior to consent. With the following more specific criteria for each of these two medications:
- •Current methadone maintenance treatment with a dose of ≥ 10mg/day, (maximum: 250mg/day), AND urinary toxicology positive for methadone and 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine (EDDP).
- •Current buprenorphine maintenance treatment with a dose of ≥ 2mg/day (maximum: 32mg/day), AND urinary toxicology positive for buprenorphine.
排除标准
- •Participants who are non-English speaking.
- •Psychiatric conditions under DSM-5 (examined with the MINI) that would make study participation unsafe, or which would prevent adherence to study procedure; examples include: suicidal (i.e. high risk for suicide on the Columbia suicide severity rating scale (C-SSRS) screen version) or homicidal ideation requiring immediate attention, inadequately-treated mental health disorder (e.g., active psychosis, uncontrolled bipolar disorder).
- •Current diagnosis of a severe substance use disorder (except for opioid and nicotine/tobacco) in the past 3 months, based on the MINI interview, that would preclude safe participation in the study as determined by the study medical clinician.
- •Signs of acute drug intoxication when arriving at the study site as determined by clinician assessment.
- •Medical or psychiatric contraindications for CBD administration (e.g., history of hypersensitivity to cannabinoids); or any of the ingredients in the product (gelatin or sesame oil).
- •Showing signs of acute opioid withdrawal symptoms (as determined by the result of the Clinical Opiate Withdrawal Scale (COWS). A Score of ≥ 5 or as interpreted by the investigator will be considered a positive result for withdrawal symptoms).
- •Have a medical condition that would make study participation unsafe, which would make treatment compliance difficult, or would prevent adherence to study procedure. This includes but is not limited to the following criteria: • < 30mL/min/1.73m2 eGFR. •QTc Fridericia > 500ms at screening. •Elevated liver enzymes at screening. The exclusionary lab values are: >4x the upper limit of normal (ULN) per laboratory criteria for AST or ALT or >1.5x ULN for bilirubin.
- •Participating in another pharmacotherapeutic trial in the past 3 months.
- •Participants who have used (within 14 days prior to consent) or plan to use (during the 24-week treatment period) any medications, dietary supplements (and/or grapefruit juice), or combination of medications and supplements known to alter the metabolism of, or interact with CBD (buproprion, rifampin, barbiturates, phenothiazines, cimetidine, anticoagulants, antiplatelets, etc.).
- •For women: being pregnant (positive urine test for pregnancy) or breastfeeding.
- •Not using an appropriate method of contraception such as hormonal contraception (oral hormonal contraceptives, Depo-Provera, Nuva-Ring), intrauterine device (IUD), sterilization, or double barrier method (combination of any two barrier methods used simultaneously, i.e. condom, spermicide, diaphragm).
- •Participants who have been court mandated to attend treatment centers
研究组 & 干预措施
1 capsule CBD (200 mg)
1 capsule 200 mg CBD 2x per day
干预措施: Cannabidiol (Drug)
2 capsules CBD (400 mg)
2 capsules 400 mg CBD 2x per day
干预措施: Cannabidiol (Drug)
1 capsule placebo and 2 capsules placebo
1 capsule 200 mg placebo 2x per day or 2 capsules 400 mg placebo 2x per day
干预措施: Placebo (Drug)
结局指标
主要结局
Percentage of study participants with negative urine toxicology for illicit opioid use
时间窗: 24 weeks
Percentage of study participants with negative urine toxicology for illicit opioid use over the course of 24 weeks.
次要结局
- Concentration of illicit opioids(Duration of the trial, 24 weeks)
- Weeks of abstinence(Duration of the trial, 24 weeks)
- Use of non-opioid illicit substances(Duration of the trial, 24 weeks)
- Duration of first opioid abstinence(Duration of the trial, 24 weeks)
- Study Retention(24 weeks)
- Opioid Craving Questionnaire (OCQ)(Every 4 weeks up to 24 weeks)
- Substance use other than opioids(Duration of the trial, 24 weeks)
- Methadone plasma concentrations(Duration of the trial, 24 weeks)
- Buprenorphine and metabolite plasma concentrations(Duration of the trial, 24 weeks)
- Retention in opioid agonist therapy(Duration of the trial, 24 weeks)
- Cue-induced Visual Analog Scale for craving (VASC)(At 12 and 24-week time points)
- Cue-induced Visual Analog Scale for anxiety (VASA)(At 12 and 24-week time points)
- Change in illicit opioids in plasma toxicology(24 weeks)
- Change in illicit opioids in urine toxicology(24 weeks)
- Generalized Anxiety Disorder Scale (GAD7)(Every 4 weeks up to 24 weeks)
研究者
Yasmin Hurd
Professor
Icahn School of Medicine at Mount Sinai