NCT07268287

Assessment of Energy Metabolism in Metabolic Myopathies

Establishment of a Platform for the in Vivo Assessment of Therapies to Treat Metabolic Myopathies, Using Biomarkers and Stable Isotope Tracers to Evaluate Energy Metabolism: A First Step Towards Monitoring the Effectiveness of Innovative Therapies.

• Status: Completed
• Phase: N/A
• Study type: Interventional
• Enrollment: 3 (actual)
• Sponsor: University of British Columbia · Academic / Other
• Sex: All
• Age: 10 Years – 18 Years
• Healthy volunteers: Not accepted

Summary

Patients with metabolic myopathies suffer from exercise intolerance due to impaired ability to produce energy and secondary de-conditioning. There is a lack of methods enabling a non-invasive assessment of muscle energy production and studies regarding the benefits of therapeutic interventions are lacking as well. In this pilot study, the main aim is to assess the benefit of an intervention: a regular at home physiotherapy program for metabolic myopathies by measuring different outcomes pre and post therapeutic intervention using minimally invasive tests. The secondary aim of this study: investigators plan to describe the results of established non-invasive stable isotope tracer tests, namely, "glucose breath test" and "doubly labelled water \& urine test" in patients pre and post 12 weeks at-home physiotherapy exercise program. The results of this study will be used for a larger scale study to assess energy metabolism in patients in patients with metabolic myopathies using non-invasive tests like breath and urine tests.

Detailed description

Metabolic myopathies are a group of genetic conditions which affect the production of energy in the muscle and are caused by muscle adenosine triphosphate (ATP) depletion. This group includes disorders of mitochondrial oxidative phosphorylation (mitochondrial myopathies, MM), fatty acid oxidation (FAOD), Pompe disease and generation of glycolytic substrates (muscle glycogenosis, GSDs) from muscle glycogen. At large, these disorders are amenable to treatment including exercise and dietary treatment and/or vitamins cofactors supplementation. There is a lack of non-invasive biomarkers which could be used to monitor treatment effectiveness. Traditionally, maximal oxygen consumption (VO2 max), quality of life questionnaire, dual-energy x-ray absorptiometry (DXA/DEXA), muscle biopsies, blood lactate and creatine kinase are used as a surrogate biomarker but have a limited validity to assess response to therapeutic interventions in patients with myopathies. The ultimate goal is to established a platform for clinical trials using minimally invasive tests to evaluate energy metabolism in patients with metabolic myopathies in response to therapeutic interventions, such as physiotherapy exercise program. These minimally invasive tests could be used to develop a platform for clinical trials for patients with muscle disease. The main aim (objective) of this study is to assess the benefit of an intervention: a 12 weeks at-home physiotherapy exercises program for metabolic myopathies by measuring different outcomes pre and post therapeutic intervention using minimally-invasive tests. The investigators will administer a 12-week at-home physiotherapy exercises program to 3 metabolic myopathies pediatric patients between age 10 and 18 years. The following outcomes will be measured pre and post intervention: 1. Glucose breath test: glucose oxidation (in mg/kg/min) measured by 13C glucose oxidation. 2. Doubly labelled water \& urine test: assess free-living total energy expenditure (in kcal). 3. Exercise test: VO2 max (in ml/kg/min). 4. Muscle content test: Muscle mass (in grams) measured by DXA. 5. Quality of life questionnaire test: Quality of life measure by PedsQL. The secondary aim (objective) of this study is to show that a glucose breath test measuring glucose oxidation (in mg/kg/min) and a doubly labelled water \& urine test measuring total energy expenditure (in kcal) are outcomes that can be used in clinical trials to evaluate therapeutic interventions, along VO2 max, DXA and quality of life questionnaires. In that regard, this is a proof-of-concept study with the aim to describe the two biomarkers results in response to a therapeutic intervention in comparison to VO2-max and DXA scan and quality of life and clinical questionnaire in 3 participants. The study design is n of 1 and will compare results of the tests pre and post therapeutic interventions in the same patients. The glucose breath test: for the glucose oxidation (in mg/kg/min) measured by 13C glucose oxidation, results will be plotted as repeated measurements (3 times pre and post-intervention) for each individual participant. Repeat measurements will reduce the intra-individual variability. A 12 weeks at-home physiotherapy exercise protocol has been developed by the investigator team physician and kinesiologists experienced with exercise, children and metabolic myopathies. The therapeutic intervention, a 12 weeks at-home physiotherapy exercises program performed at least 5 times per week, under virtual supervision 3 times per week by a kinesiologist, contains the same type of exercises that are normally prescribed to this population on a clinical basis. All patients will perform the same program to reduce inter-variability. In parallel, clinical methods such as VO2max, PedsQL and DXA will be measured pre- (baseline) and post-intervention evaluation. The investigators consulted a BCCHRI statistician with regard to the data analysis. Statistical analysis will include the intra-individual data analysis (n=1 study design) and will compare - using a Paired T test -the pre- and post- intervention data obtained from the two stable isotope tracer methods, VO2 max, DXA and quality of life questionnaires. The results of these tests will also be descriptively analyzed and the pre and post-intervention results will be plotted graphically. The results of this proof of concept study will inform a larger scale project that was initially planned.

Conditions

• Metabolic Myopathies

Interventions

Type	Name	Description
OTHER	12-week Physiotherapy Intervention	A 12 week at-home physiotherapy exercises program performed at least 5 times per week, under virtual supervision 3 times per week by a kinesiologist, contains the same type of exercises that are normally prescribed to this population on a clinical basis. All patients will perform the same program to reduce inter-variability.
DIETARY_SUPPLEMENT	13C-Glucose Breath Test	Experiment piece 1: Oral glucose isotope is administered to fasted participants on pre and post-intervention study days. Breath is collected over a 4-hour period following ingestion. Other Names: • D-glucose (Thermo Scientific™ NERL™ Trutol™)
DIETARY_SUPPLEMENT	Doubly labelled water & urine test	Experiment piece 2: 1 study day pre and post-intervention fasted participants ingest a single oral dose of doubly labelled water (2H218O) isotope. 4 urine samples are collected over a 4 hour period following isotope administration, and once a day over 14 days. DLW is a safe and minimally invasive technique, considered the gold standard for precise measurement energy expenditure in humans. It involves enriching the body water with heavy hydrogen and oxygen (2H218O). The method is based on the principle that the 2H2 derived from body water is eliminated only as water (2H2O), while 18O is eliminated as both water (H2 18O) and carbon dioxide (C18O2).
DIAGNOSTIC_TEST	Clinical Assessments - Exercise Test	Experiment piece 3: Using a well-established clinical method VO2 max, once pre and post-intervention to assess for body composition (oxygen consumption during exercise).
DIAGNOSTIC_TEST	Clinical Assessment - Muscle Content	Experiment piece 3: Using a well-established clinical method, DXA, once pre and post-intervention to assess for body muscle content (lean muscle mass)
DIAGNOSTIC_TEST	Clinical Assessment - Quality of Life	Experiment piece 3: Using a well-established clinical survey, PedsQL, once pre and post-intervention to assess for participants perception of quality of life.

Timeline

• Start date: 2022-06-26
• Primary completion: 2024-05-24
• Completion: 2025-10-08
• First posted: 2025-12-05
• Last updated: 2025-12-05

Locations

1 site across 1 country: Canada