Pompe disease Nutritional, Metabolic, Endocrine
Conditions
Interventions
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-onse
Sponsors
Newcastle upon Tyne Hospitals NHS Foundation Trust
Eligibility
Sex/Gender
All
Age
18 Years to 120 Years
Inclusion criteria
Inclusion criteria: 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.
Exclusion criteria
Exclusion criteria: 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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| MRI-derived thigh muscle structure and composition measured using fat fraction, cross-sectional area, contractile cross-sectional area and muscle water T2 relaxation time of the thigh muscles measured using 3-point Dixon MRI and muscle water T2 MRI, at baseline, Year 1 and Year 2 for participants with late-onset Pompe disease, and baseline only for healthy controls;Muscle glycogen content in the muscles of the left lower limb measured using carbon-13 magnetic resonance spectroscopy at baseline, Year 1 and Year 2 for participants with late-onset Pompe disease, and baseline only for healthy controls;Pivotal sub-study: short-term variation in thigh muscle glycogen content across the routine enzyme replacement therapy infusion cycle measured using carbon-13 magnetic resonance spectroscopy in a subset of three participants with late-onset Pompe disease at Day 1 after routine enzyme replacement therapy infusion, Day 7 after infusion, and Day 14 after infusion | — |
Secondary
| Measure | Time frame |
|---|---|
| Skeletal muscle functional outcomes measured using standardised functional assessments, including RPACT, 100-metre timed test, 10-metre walk-carrying test, Timed Up and Go, North Star Assessment for Limb-Girdle Type Muscular Dystrophies, Performance of Upper Limb entry item, Biering-Sorenson back extensor test, handheld dynamometry, 6-minute walk test, and gait analysis at baseline, Year 1 and Year 2 for participants with late-onset Pompe disease, and baseline only for healthy controls;Pulmonary function outcomes measured using spirometric and respiratory pressure measures, including seated forced vital capacity, supine forced vital capacity, maximal inspiratory pressure and maximal expiratory pressure, at baseline, Year 1 and Year 2 for participants with late-onset Pompe disease, and baseline only for healthy controls;Biomarkers measured using blood and urine samples collected and stored in the JWMDRC Biobank for future research, where authorised by participant consent, at baseline, Year 1 and Year 2 for participants with late-onset Pompe disease, and baseline only for healthy controls | — |
Countries
England, United Kingdom
Contacts
Public ContactAlejandro Gonzalez Chamorro
Outcome results
None listed