Ecstasy to Alleviate SEvere Chronic Neuropathic... — Clinical Trial Details | Blossom
Clinical TrialChronic PainMDMAPlaceboRecruiting
Ecstasy to Alleviate SEvere Chronic Neuropathic Pain Trial
This Phase II, randomised, triple-blinded, parallel trial (n=40) will evaluate the feasibility, tolerability and preliminary efficacy of a single oral dose of MDMA for adults with moderate-to-severe chronic neuropathic pain. The primary purpose is to determine feasibility for a larger multi-centre trial by assessing recruitment, data completion, blinding integrity and drug-related adverse events, while secondary aims include preliminary assessment of pain interference and other clinical outcomes at 16 weeks.
Participants are randomised to a treatment arm receiving MDMA 120 mg (3 × 40 mg capsule) orally as a single dose with psychological support and an optional 40 mg supplemental dose at 2 hours (maximum 160 mg), or to an active-placebo arm receiving methylphenidate 30 mg (3 × 10 mg capsule) orally with an optional 10 mg supplemental dose at 2 hours (maximum 40 mg). Preparatory psychotherapy is delivered in the weeks before dosing, the combined dosing and psychotherapy session occurs at week 6, and integrative psychotherapy follows through weeks 7–16; adjunctive home psychotherapy modules are also used. Key outcomes include feasibility metrics and clinical measures such as PROMIS Pain Interference (primary clinical signal at 16 weeks), pain intensity, physical function, emotional function, overall improvement ratings and adverse events; each participant is followed for 16 weeks and the total study duration is 2 years.
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).
Study Arms & Interventions
3,4-Methylenedioxymethamphetamine
active comparator
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)
Interventions
MDMA
Locations
St. Michael's Hospital — Toronto, Ontario, Canada
Methylphenidate
inactive
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)
Interventions
Placebo
Unmatched intervention: Methylphenidate
Participants
Ages
18 – ?
Sexes
Male & Female
BMI
-
Psychosis History
-
Inclusion Criteria
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.
Exclusion Criteria
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
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.