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Updated: Jan 7, 2026
Author Spotlight: Methodologies and Advancements of Chronic Pain Management Research
Published on: January 5, 2024
Memantine and graded motor imagery for complex regional pain syndrome (MEMOIR): study protocol and statistical
Michael C Ferraro1,2, Yannick L Gilanyi3,4, Eric J Visser5
1School of Health Sciences, Faculty of Medicine and Health, University of New South Wales, Sydney, Australia. m.ferraro@neura.edu.
Background:
Complex regional pain syndrome (CRPS) is a rare chronic pain condition characterised by severe pain, sensory, motor, autonomic, and trophic abnormalities. Effective treatment options are limited, and international guidelines rely on low-quality evidence and consensus. Two interventions-memantine, an N-methyl-D-aspartate receptor antagonist, and graded motor imagery, a rehabilitation approach targeting sensorimotor processing-have shown promise in pilot studies but lack definitive evaluation in large-scale trials. MEMOIR aims to evaluate the benefits and harms of memantine and graded motor imagery for CRPS.
Methods:
MEMOIR is a fully decentralised, 2 × 2 factorial, randomised trial comparing memantine with placebo and graded motor imagery with no graded motor imagery in adults with CRPS. A total of 204 participants with CRPS of 6 months to 5 years duration will be randomised to one of four groups: (i) memantine and graded motor imagery, (ii) memantine only, (iii) placebo and graded motor imagery, or (iv) placebo only. Memantine will be administered at 40 mg/day (or maximum tolerated dose); graded motor imagery will comprise seven 1-h sessions delivered via telehealth. The treatment period is 16 weeks. The dual primary outcomes are pain intensity (11-point numeric rating scale) and PROMIS pain interference assessed at 16 weeks. Secondary outcomes include physical function, fatigue, cognitive function, depressive symptoms, self-efficacy, health-related quality of life, CRPS severity, healthcare use, and adverse events. The follow-up period is 52 weeks. The estimands of interest are the mean effect of memantine compared to placebo and the mean effect of graded motor imagery compared to no graded motor imagery on all outcomes. All analyses will follow the intention-to-treat principle.
Discussion:
MEMOIR will be the largest investigator-initiated CRPS trial to date. The 2 × 2 factorial design and decentralised delivery aim to maximise efficiency, accessibility, and equity. If effective, memantine and graded motor imagery represent scalable, low-cost treatments that can be given in clinics or at home, with the potential to transform CRPS management.
Trial Registration:
Australian New Zealand Clinical Trials Registry ( ACTRN12621000175875 ). Registered on 12 February 2021.
