PRISM: a single-centre prospective longitudinal observational cohort study of patients with Pompe disease treated with enzyme replacement therapy using muscle MRI and muscle function tests
Pompe disease
PRISM is a single-centre, prospective, longitudinal, observational cohort study conducted in the JWMDRC, in Newcastle upon Tyne, UK. The study recruits 40 adult participants: 30 adults with late-onset Pompe disease (LOPD) who are already receiving licensed enzyme replacement therapy (ERT) as part of routine clinical care, and 10 age- and sex-matched healthy controls. Participants with late-onset Pompe disease are observed in two cohorts according to the licensed ERT they are already receiving in routine care: cipaglucosidase alfa plus miglustat or avalglucosidase alfa. The study does not administer, assign, modify or compare treatment. A small pivotal sub-study is conducted before the main longitudinal phase. Three of the 30 participants with LOPD disease receiving routine fortnightly ERT undergo carbon-13 magnetic resonance spectroscopy at three timepoints within a single infusion cycle: Day-1 after infusion, Day-7 after infusion, and Day-14 after infusion. This assesses whether the timing of spectroscopy in relation to routine enzyme replacement therapy infusion influences muscle glycogen measurements and informs the timing of subsequent spectroscopy assessments in the longitudinal phase. Participants with LOPD attend study assessments at baseline, Year 1 and Year 2. Healthy controls attend a single baseline visit only. At each relevant visit, participants undergo muscle MRI and carbon-13 magnetic resonance spectroscopy to assess thigh muscle structure, fat fraction, muscle water T2 relaxation time and muscle glycogen content in the left lower limb. Clinical and functional assessments include demographic and disease history data collection, medical history, concomitant medication review, adverse event and serious adverse event review, patient-reported outcome measures, the 100-metre timed test, the 10-metre walk-carrying test, Timed Up and Go, the North Star Assessment for Limb-Girdle Type Muscular Dystrophies, Performance of Upper Limb entry item, the Biering
1. Adults aged 18 years or over 2. Able and willing to provide informed consent 3. Ambulatory, able to walk with or without assistive devices 4. No contraindications to MRI 5. Able and willing to complete the relevant study assessments, including MRI and carbon-13 magnetic resonance spectroscopy, muscle function tests, pulmonary function tests where applicable, gait analysis, questionnaires, wearable monitoring where applicable, and blood and urine sample collection 6. For participants with late-onset Pompe disease: 6.1. Confirmed diagnosis of late-onset Pompe disease, based on recommendations recently proposed by the European Pompe Consortium: reduced enzymatic activity in leukocytes, fibroblasts or skeletal muscle and/or by the presence of two mutations in the GAA gene 6.2. Symptoms started after 2 years of age and are compatible with a clinical diagnosis of late-onset Pompe disease 6.3. Receiving licensed enzyme replacement therapy (ERT) as part of routine clinical care (either cipaglucosidase alfa plus miglustat or avalglucosidase alfa) 6.4. Medical Research Council quadriceps muscle score of 3 or above 7. For healthy controls: adults without Pompe disease who are age- and sex-matched to participants with late-onset Pompe disease.
1. Contraindications for MRI such as having a metallic prosthesis, pacemaker or any other device that makes the completion of an MRI impossible 2. Having claustrophobia or other conditions that could limit the capacity of the patient to be located inside the MRI 3. Inability to lie supine for up to 60 min 4. Unwillingness to complete all study-related activity 5. Pregnancy, for female participants of childbearing potential 6. Inability to understand the study information or provide informed consent 7. Any other reason which, in the opinion of the study team, makes participation unsuitable