Ecstasy to Alleviate SEvere Chronic Neuropathic Pain Trial

What this study is about

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, triple blinded study. 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).

Who can join (things the study team will check)

✅ You may be able to join if…

• 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.

🚫 You may not be able to join if…

• 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

+ 11 more criteria — see the full checklist in the app.

Where this trial is running

• St. Michael's Hospital, Toronto, Ontario, Canada

Who to contact

Akash Goel, MD,MPH,FRCPC · 4168645071 · Akash.Goel@unityhealth.to

It's completely normal to call and ask questions before deciding anything. Mention the study ID: NCT07301632.