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.
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 3
- 试验地点
- 2
- 主要终点
- Glucose Oxidation
研究概览
简要总结
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.
详细描述
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:
- Glucose breath test: glucose oxidation (in mg/kg/min) measured by 13C glucose oxidation.
- Doubly labelled water & urine test: assess free-living total energy expenditure (in kcal).
- Exercise test: VO2 max (in ml/kg/min).
- Muscle content test: Muscle mass (in grams) measured by DXA.
- Quality of life questionnaire test: Quality of life measure by PedsQL.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Single Group
- 主要目的
- Basic Science
- 盲法
- None
入排标准
- 年龄范围
- 10 Years 至 18 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Confirmed diagnosis of the following: Mitochondrial Metabolic Myopathy (mMM), Fatty Acid Oxidation Disorder (FAOD), Pompe disease, or muscle Glycogen Storage Disease (GSD) (McArdle) via demonstration of deficient enzyme activity and / or demonstration of molecular testing confirming respective pathogenic variants and or compatible with disease phenotype.
- •Age ≥10 years up to 18 years.
- •Any gender.
- •No past history of rhabdomyolysis requiring hospitalization.
- •No signs or symptoms of infectious disease at least 14 days prior to the commencement of study visit (to mitigate the risk of rhabdomyolysis and coronavirus transmission).
- •Participant must speak/understand English.
- •Participant must have a smart phone or a tablet with a provider plan or that can be linked to Wi-Fi.
- •Participant must have the time to commit to 11 visits at BC Children's Hospital over 21 weeks.
排除标准
- •Any concurrent disorders / conditions that would interfere with /impact the study procedure (breath test and/or low intensity exercise).
- •Diabetes Mellitus type I or II.
- •Abnormal Cardiac assessment: cardiomyopathy or arrhythmia not allowing physical exercise.
研究组 & 干预措施
13C-Glucose Breath Test
Experiment piece 1:
3 study days (pre-physio intervention) - single oral dose of unlabeled glucose and U-13C-glucose isotope.
3 study days (post-physio intervention) - single oral dose of unlabeled glucose and U-13C-glucose isotope. Both in mg/kg/min.
干预措施: 13C-Glucose Breath Test (Dietary Supplement)
Doubly Labelled Water & Urine Test
Experiment piece 2:
1 study day (pre-physio intervention) - single oral dose of doubly labelled water (2H218O) isotope.
1 study days (post-physio intervention) - single oral dose of doubly labelled water (2H218O) isotope. Assess free-living total energy expenditure (in kcal).
干预措施: Doubly labelled water & urine test (Dietary Supplement)
12-week Physiotherapy Intervention
Performed once by all participants, in between the pre- and post-intervention experiments described in the other arms.
干预措施: 12-week Physiotherapy Intervention (Other)
Clinical Assessments - Exercise Test
Experiment piece 3:
1 study day (pre-intervention) and 1 study day (post-intervention).
Exercise test: Maximum oxygen consumption (VO2 max) (in ml/kg/min).
干预措施: Clinical Assessments - Exercise Test (Diagnostic Test)
Clinical Assessments - Muscle Content
Experiment piece 3:
1 study day (pre-intervention) and 1 study day (post-intervention).
Muscle content test: Muscle mass measured by Dual-Energy X-ray Absorptiometry (DXA/DEXA) (in grams).
干预措施: Clinical Assessment - Muscle Content (Diagnostic Test)
Clinical Assessments - Quality of Life Questionnaire
Experiment piece 3:
1 study day (pre-intervention) and 1 study day (post-intervention).
Quality of life questionnaire test: Quality of life measure by pediatric quality of life questionnaire (PedsQL).
干预措施: Clinical Assessment - Quality of Life (Diagnostic Test)
结局指标
主要结局
Glucose Oxidation
时间窗: 4 Hours
Breath samples will be collected during the 3 pre and post-intervention study days to measure the rate of oxidation of 13C glucose (mg/kg/min).
Glucose Oxidation
时间窗: 4 Hours
Breath samples will be collected during the 3 pre and post-intervention study days to measure the rate of oxidation of 13C glucose (mg/kg/min).
次要结局
- Doubly Labeled Water Free-living Total Energy Expenditure(14 Days)
- Clinical Assessments - Exercise Test(1-2 Hours)
- Doubly Labeled Water Free-living Total Energy Expenditure(14 Days)
- Clinical Assessments - Exercise Test(1-2 Hours)
- Clinical Assessments - Muscle Content(1 Hour)
- Clinical Assessments - Quality of Life(30 minutes)
研究者
Rajavel Elango, PhD
Principal Investigator
University of British Columbia