None listed
Conditions
Brief summary
MEMOIR aims to evaluate the efficacy of oral memantine and the effectiveness of Graded Motor Imagery (GMI) on pain intensity and pain interference at 16 weeks in people with chronic Complex Regional Pain Syndrome, in a 2 x 2 factorial RCT. Participants will be randomised to one of 4 groups: memantine plus GMI; memantine plus usual care; placebo memantine plus GMI; placebo memantine plus usual care. We hypothesise that memantine and GMI will produce clinically meaningful reductions in pain intensity and pain interference.
Interventions
Intervention 1: Memantine
Target dose of 40mg/day or maximum tolerated dose, administered in 10mg tablets, twice daily. Total duration of treatment = 16 weeks. The treatment regime comprises 4 weeks up-titration (5mg/day for 4 days; 10mg/day for 4 days; 15mg/day for 4 days, 20mg/day for 4 days; 25mg/day for 4 days; 30mg/day for 4 days; 35mg/day for 4 days) 8 weeks maintenance dose (40mg/day) and 4 weeks wash-out (35 mg/day for 4 days; 30mg/day for 4 days; 25 mg/day for 4 days; 20mg/day for 4 day
Intervention 1: Memantine Target dose of 40mg/day or maximum tolerated dose, administered in 10mg tablets, twice daily. Total duration of treatment = 16 weeks. The treatment regime comprises 4 weeks up-titration (5mg/day for 4 days; 10mg/day for 4 days; 15mg/day for 4 days, 20mg/day for 4 days; 25mg/day for 4 days; 30mg/day for 4 days; 35mg/day for 4 days) 8 weeks maintenance dose (40mg/day) and 4 weeks wash-out (35 mg/day for 4 days; 30mg/day for 4 days; 25 mg/day for 4 days; 20mg/day for 4 days; 15 mg/day for 4 days; 10mg/day for 4 days; 5mg/day for 4 days). Participants will be provided with a pill cutters to allow halving of tablets during the up-titration and wash-out periods. Adherence to memantine will be measured via daily self-report medication diaries and via pill counting in returned medication kits. Intervention 2: Graded Motor Imagery (GMI) A progressive rehabilitation program thought to sequentially activate brain regions associated with motor planning and execution. Participants will receive 7, 1-hour sessions delivered over 16 weeks via Telehealth by an experienced physiotherapist/occupational therapist/exercise physiologist directly to the participant's home. The first 4 sessions will be scheduled approximately fortnightly and the final 3 sessions will be scheduled approximately every 3 weeks. Participants will be prescribed approximately 1 hour of home activities daily. The treatment program includes implicit and explicit motor imagery; mirror therapy; simple, complex and functional graded movements; goal-setting; and pain education. Participants will complete activities at a self-directed pace following a standard progression protocol with mandatory advancement at each Telehealth treatment session. Participants will be provided with an education book (developed specifically for this study), access to an E-learning platform with educational and rehabilitation activities, access to the Recognise App, Recognise Flash Cards and Mirror Box (NOI, Adelaide). Participant adherence will be measured via session attendance and self-report therapy diaries. The clinician will undergo approximately 20 hours of online training in Graded Motor Imagery, pain education, goal setting and specifically for familiarisation with the treatment protocol. The clinician will be provided with a clinician manual and have access to clinical supervision. Clinician fidelity to the treatment curriculum will be measured via evaluation of recorded Telehealth sessions 1, 2 and 4. There are 4 arms in this 2x2 factorial trial: Arm 1. Memantine plus GMI Arm 2. Memantine plus usual care Arm 3. Placebo memantine plus GMI Arm 4. Placebo memantine plus usual care
Sponsors
Neuroscience Research Australia
Study design
Allocation
Randomised controlled trial
Intervention model
Factorial
Primary purpose
Treatment
Masking
Blinded (masking used) (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Diagnosis of unilateral, chronic CRPS according to the Budapest research criteria, of 6 months to 5 years duration; at least moderate pain and disability measured by SF-36 items 7 and 8; English language proficiency; access to internet; willingness to provide informed consent.
Exclusion criteria
Known allergies to NMDA receptor antagonists; taking more than 60mg/day of morphine equivalents of opioid analgesics; taking methadone; using more than 450mg/day of pregabalin or more than 1200mg/day gabapentin; using monoamine oxidase inhibitors; using more than 50mg/day of tricyclic antidepressants; having used ketamine in the preceding 4 weeks; having received lidocaine injections or infusions in the preceding 4 weeks; commencement of bisphosphonate therapy in the preceding 4 months; taking anti-arrhythmic cardiac medications; taking anti-psychotic medications; taking cisapride; taking erythromycin; taking quinolones; taking anti-tuberculous agents; taking anti-fungal agents; taking antiretrovirals; uncontrolled hypertension; moderate to severe renal impairment (defined as an estimated Glomerular Filtration Rate below 70mL/min/1.73m2); diagnosis of prolonged QTc syndrome; ventricular fibrillation; ventricular tachycardia; heart block; Torsades de Pointes; acute coronary syndrome in the preceding 3 months; NYHA Classes III-IV heart failure; implanted pacemaker or defibrillator; history of serious neurological conditions (stroke, seizure disorders, Alzheimer’s disease, paralysis); history of schizophrenia, psychosis, bipolar disorder, or clinically significant delusions, hallucinations or delirium; implanted spinal cord or nerve stimulators; females who are pregnant or lactating; females of child-bearing potential and not using reliable contraceptive method(s); males and females planning conception; significant history of illicit substance abuse or drug overuse; current use of Graded Motor Imagery; other pain that may interfere with assessment of CRPS and/or use of Graded Motor Imagery, according to the study physician; scheduled for major surgery during the treatment or follow-up period.
Outcome results
None listed