Ecstasy to Alleviate SEvere Chronic Neuropathic Pain (EASE Pain) Trial: A Randomized Controlled Pilot Trial
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 50
- 试验地点
- 1
- 主要终点
- The primary outcome of this pilot trial is to determine feasibility of a large-scale, multi-center trial.
研究概览
简要总结
This is a Health Canada regulated internal pilot study designed to assess the feasibility, tolerability, and preliminary efficacy of 3, 4-methylenedioxymethamphetamine hydrochloride capsules-AT for chronic neuropathic pain to inform a larger, fully powered multi-center study. This is an interventional, randomized, 2-arm parallel, blinded (Treating and dosing physician, Patient Outcome assessor and psychotherapist).
The total study duration is 2 years.
Participants will receive preparatory psychotherapy session during week 2 and week 4 followed by a combined single dosing session with psychotherapy during week 6. Integrative psychotherapy will follow at weeks 6, 8, 12, and 16.
Follow up for primary clinical endpoint at week 16; final follow up for secondary clinical endpoint at 16-weeks.
Participants will be asked to complete adjunctive home psychotherapy in the form of online modules. Data collected will be entered in electronic case report form (REDCap Academic).
详细描述
Primary objective:
To demonstrate the feasibility of conducting the full EASE Pain trial by achieving targets in recruitment, data completion rate, blinding integrity, minimal serious drug-related adverse events, and by identifying barriers and facilitators to the full trial.
Secondary objectives (full trial):
To evaluate whether a 120 mg dose of oral 3,4-methylenedioxymethamphetamine with an optional 40mg supplementary dose leads to meaningful improvements in pain interference at 16-weeks in patients with moderate-to-severe chronic neuropathic pain compared to active-placebo, and assess changes in physical function, physical activity, emotional function, overall rating of improvement, and adverse events over 16 weeks.
Study type: Intervention trial Allocation: Randomized Intervention model: 2-Arm Parallel Group Primary purpose: Feasibility Phase: Phase II Blinding: Treating and dosing physician, Patient, Outcome assessor, and Psychotherapist
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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Consenting adults 18 years and older.
- •Diagnosis of chronic neuropathic pain (greater than 3 months in duration) by a clinician with specialized training in chronic pain, confirmed with the standardized Leeds Assessment of Neuropathic Symptoms and Signs questionnaire.
- •Suffering from moderate-to-severe pain as defined by
- •Baseline Patient Reported Outcomes Measurement System - Pain Interference (PROMIS-PI) score of greater than or equal to 60
- •An average pain intensity of greater than or equal to 5 on a 0-10 numeric rating scale,43
- •Treatment-refractory pain as defined by a failure of ≥2 medications recommended in the Canadian consensus guidelines on the management of CNP to generate self-reported meaningful improvement in symptoms.
- •For participants of childbearing potential, use of a highly effective or double-barrier methods of contraception. Abstinence is acceptable if it is the preferred and usual lifestyle of the participant.
- •Sufficient English skills to participate in psychotherapy.
排除标准
- •Past or current history of a psychotic disorder, mania, hypomania, bipolarity, current suicidal ideation, stimulant use disorder (i.e., cocaine, amphetamine, methamphetamine, MDMA, methylphenidate (Ritalin), etc , and any other substance use disorder within the past 12 months assessed by history and confirmed the Mini-International Neuropsychiatric Interview [MINI]. Other secondary psychiatric comorbidities (e.g., anxiety disorders, trauma related disorders, other personality disorders. etc.) will not be excluded
- •Participants with a history of suicide attempts are not excluded unless a significant risk of suicidal behavior is present at the time of screening as determined by the CRSS (Columbia suicide rating scale)
- •History of prior MDMA use (excluded to maintain blinding integrity)
- •Long QT syndrome, measured by an ECG with a QTc more than 450 ms for males, and 470 ms for females.
- •Presence of a relative or absolute contraindication to MDMA or Methylphenidate:
- •Pre-existing cardiovascular disorders evidenced in clinical records or disclosed on patient self-report, such as: uncontrolled hypertension (sustained blood pressure ≥160/100 mmHg), angina (ongoing angina at rest, recent hospitalization for acute coronary syndrome within the past 3 months, or a history of revascularization (e.g., stenting or bypass surgery) within the past 6 months), arterial occlusive disease; heart failure, hemodynamically significant congenital heart disease, cardiomyopathies, myocardial infarction (within the past 6 months), potentially life-threatening arrhythmias (new-onset within the last 3 months), arrhythmias causing hemodynamic instability (SBP < 90 mm Hg), or requiring urgent intervention (e.g., atrial fibrillation with rapid ventricular response or ventricular tachycardia), channelopathies, aneurysmal vascular disease (e.g., thoracic and/or abdominal aorta, intracranial, and peripheral arterial vessels), advanced arteriosclerosis
- •Cerebrovascular conditions: acute stroke or recent history of intracerebral hemorrhage (ischemic or hemorrhagic stroke occurring within the past 6 months)
- •Conditions at risk of elevation of blood pressure and increase heart rate, such as glaucoma, tension, agitation, thyrotoxicosis, pheochromocytoma
- •Motor tics and/or family history or diagnosis of Tourette's syndrome
- •Moderate to severe chronic kidney disease or kidney failure, such as requiring dialysis, significant treatment adjustments for kidney function, or regular nephrologist follow-up)
- •Moderate to severe liver disease, such as cirrhosis, a history of significant jaundice unrelated to temporary illness, or any liver condition requiring regular monitoring by a specialist).
- •Current treatment with selective serotonin reuptake inhibitors (SSRI's) and serotonin-norepinephrine reuptake inhibitors (SNRI's), tricyclic antidepressants, serotonin 5-HT1 receptor agonists (triptans) and 5-HT3 receptor antagonist antiemetics (risk of Serotonin Syndrome)
- •Hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption (methylphenidate contains lactose)
- •Seizure disorders
- •Pregnancy, or breastfeeding
- •Known hypersensitivity to study drugs or any study drug excipients
- •Medications that interact with study drugs including:
- •Any lifetime history use of any stimulant medication (e.g., Adderall, Vyvanse, Ritalin)
- •Caffeine intake within 24 hours
- •Monoamine oxidase inhibitors (MAOI) within 14 days (e.g. phenelzine, moclobemide, isoniazid, linezolid, phenelzine, harmine) due to risk of hypertensive crisis
- •CYP2D6 substrates and modifiers (such as: buproprion, fluoxetine, paroxetine, duloxetine, mirabegron).
- •Adrenergic agents (e.g. clonidine) risk of sudden death
- •Vasopressor agents (ephedrine pseudoephedrine)
- •Coumarin anticoagulants (e.g., warfarin),
- •Anticonvulsants (e.g., phenobarbital, diphenylhydantoin, primidone)
- •Anti-psychotics and inhibitors of dopamine uptake (e.g. haloperidol, DOPA, tricyclic antidepressants)
- •Concomitant medication that could prolong ECG QT interval (e.g. ondansetron, risperidone, methadone)
- •Selective Serotonin Reuptake Inhibitors (citalopram, sertraline, fluvoxamine, escitalopram)
- •Selective Norepinephrine Uptake Inhibitors (e.g. venlafaxine, duloxetine); Serotonergic Drugs (e.g. dextromethorphan, fentanyl, St. John's Wort, tramadol, 5-hydroxytryptophan); serotonin 5-HT1 receptor agonists (triptans) and 5-HT3 receptor antagonist antiemetics due risk of Serotonin Syndrome which is a potentially life- threatening condition
- •Currently engaged in psychotherapy for CNP (other psychotherapy for non-CNP is allowed).
- •Any other clinically significant medical illness that, in the opinion of the investigator, may interfere with the interpretation of the study results or constitute a health risk for the participant if they take part in the study.
研究组 & 干预措施
3,4-Methylenedioxymethamphetamine
Treatment Arm: 3,4-Methylenedioxymethamphetamine 120mg (3 x 40mg capsule) PO single dose plus psychological support; optional 40mg supplemental dose at 2hr mark if there are no tolerability issues reported, patient consents and lead physician deems appropriate. (Maximum dose 160mg)
干预措施: 3,4-Methylenedioxymethamphetamine (Drug)
Methylphenidate
Placebo arm: Methylphenidate 30mg (3 x 10mg capsule) PO single dose plus psychological support; optional 10mg supplemental dose at 2hr mark if there are no tolerability issues reported, patient consents and lead physician deems appropriate. (Maximum dose of 40 mg)
干预措施: Methylphenidate (Drug)
结局指标
主要结局
The primary outcome of this pilot trial is to determine feasibility of a large-scale, multi-center trial.
时间窗: 16 weeks
Average Monthly recruitment of \>1 participant per center means that the full trial should meet recruitment requirements within 12 months.
Secondary feasibility outcome
时间窗: 16 weeks
Data completion rate (of primary clinical outcome)≥ 80%
Participant Retention
时间窗: 16 weeks
Retention of ≥80% of participants at the reported primary outcome point of 16 weeks after the experimental session should minimize attrition bias in the definitive trial's primary outcome data (e.g. withdrawal due to side-effects)
Blinding
时间窗: 16 weeks
Blinding Integrity (≤80% of participants in both arms correctly guess their treatment allocation (Note: 50% of participants would be expected to correctly guess treatment allocation due to chance alone)
Adverse Events
时间窗: 16 weeks
≤3 serious drug-related adverse events
Secondary Feasibility Outcome
时间窗: 16 weeks
identification of patient, clinician and researcher-identified trial barriers using qualitative methods (e.g. interviews at the end of the study with participants who provides consent )
次要结局
- The Patient-Reported Outcomes Measurement Information System (PROMIS) pain Intensity, Pain Interference and Physical Function Scale(Week 1, Week 7, Week 11 and Week 16)
- Patient Health Questionnaire (PHQ-9)(Week 1, Week 7, Week 11 and Week 16)
- The Post traumatic Stress Disorder Checklist for Diagnostic and Statistical Manual for Mental Disorder-5 (PCL-5)(Week 1, Week 7, Week 11 and Week 16)
- Generalized Anxiety Disorder 7-Item (GAD-7) Questionnaire(Week 1, Week 7, Week 11 and Week 16)
- Health Questionnaire (EQ-5D-5L)(Week 1, Week 7, Week 11 and Week 16)
- The Patient Global Impression of Change Scale (PGIC)(Week 7, Week 11 and Week 16)
- The Toronto Side Effect Scale (TSES)(Week 7, Week 11 and Week 16)
- STAR-P(Week 7, Week 11 and Week 16)
- Subjective Drug Effects (VAS)(Week 6)