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).
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 Total study duration: 2 years Duration for each subject: 16 weeks. Preparatory psychotherapy from week 1 to 5; a single dosing session with psychotherapy at week 6 and integrative psychotherapy at weeks 7 to 16. Follow up for primary clinical endpoint and final follow up at week 16. Dosage regimen: 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) 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) Treatment/ assessment visits: Week -1: Screening Week 1: Baseline data collection, psychotherapy workbook 1 (preparation) Week 2: Psychotherapy preparatory session 1 Week 3: Psychotherapy workbook 2 (preparation) Week 4: Psychotherapy preparation session 2 Week 5: Psychotherapy workbook 3 (preparation) Week 6: (Day 0): Randomization to drug and experimental session with in-person psychotherapy (Day 1) Psychotherapy integration session 1 Week7: Psychotherapy workbook 4 (integration). Questionnaire and AE follow up Week 8: Psychotherapy integration session 2 Week 9 to 11 Psychotherapy workbook 5 (integration) Week 10: Questionnaire and AE follow up Week 12: Psychotherapy integration session 3 Week 13 to 15: Psychotherapy workbook 6 (integration) Week 16: Psychotherapy integration session 4. Primary clinical end point (Questionnaires and Adverse Event (AE) follow up)
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
50
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)
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)
St. Michael's Hospital
Toronto, Ontario, Canada
RECRUITINGThe primary outcome of this pilot trial is to determine feasibility of a large-scale, multi-center trial.
Average Monthly recruitment of \>1 participant per center means that the full trial should meet recruitment requirements within 12 months.
Time frame: 16 weeks
Secondary feasibility outcome
Data completion rate (of primary clinical outcome)≥ 80%
Time frame: 16 weeks
Participant Retention
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)
Time frame: 16 weeks
Blinding
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)
Time frame: 16 weeks
Adverse Events
≤3 serious drug-related adverse events
Time frame: 16 weeks
Secondary Feasibility Outcome
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 )
Time frame: 16 weeks
The Patient-Reported Outcomes Measurement Information System (PROMIS) pain Intensity, Pain Interference and Physical Function Scale
In the past 7 days patients to rate their pain on average- 0 scale-indicates No pain and 10 scale- indicates Worst imaginable pain
Time frame: Week 1, Week 7, Week 11 and Week 16
Patient Health Questionnaire (PHQ-9)
Over the last 2 weeks how often the patient has been bothered by daily activities on a scale of 0 to 3. 0 (Not at all) and 3 (Nearly every day)
Time frame: Week 1, Week 7, Week 11 and Week 16
Generalized Anxiety Disorder 7-Item (GAD-7) Questionnaire
Over the last 2 weeks, how often patients have been bothered by anxiety on a scale of 0 to 3. 0 equals Not at all and 3 equals Nearly every day
Time frame: 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)
Over the past month, how patients were bothered by internal and external feelings like stress, negativity etc. This is measured on a scale of 0 (Not at all) to 4 (Extremely)
Time frame: Week 1, Week 7, Week 11 and Week 16
Health Questionnaire (EQ-5D-5L)
Patients to describe how their health is affected in terms of mobility, self-care, Usual activities like (work, study, family), Pain/Discomfort, Anxiety/Depression on a scale of 0( Worst health you can imagine) to 100 (Best health you can imagine)
Time frame: Week 1, Week 7, Week 11 and Week 16
The Patient Global Impression of Change Scale (PGIC)
This questionnaire measures how the patient impression changed before being enrolled in the study. Measured in a scale of 1 (Very much Improved) to 7 ( Very Much Worse)
Time frame: Week 7, Week 11 and Week 16
The Toronto Side Effect Scale (TSES)
This questionnaire measures patient's symptoms in the last two weeks for Agitation, tremor, twitching etc in terms of frequency and Severity in a scale of 1 (Never) to 5 (Every day)
Time frame: Week 7, Week 11 and Week 16
STAR-P
This questionnaire measures patient's perception and attitude regarding the clinician on a scale of 0 (Never) to 4 (Always)
Time frame: Week 7, Week 11 and Week 16
Subjective Drug Effects (VAS)
On a scale of 0 (Not at all) to 10 (Extremely) patients to describe their experience during intervention session regarding the subjective drug effects
Time frame: Week 6
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.