Assessment of Energy Metabolism in Metabolic Myopathies

NCT ID: NCT07268287

Last Updated: 2025-12-05

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

NA

Total Enrollment

3 participants

Study Classification

INTERVENTIONAL

Study Start Date

2022-06-26

Study Completion Date

2025-10-08

Brief Summary

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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

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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

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Metabolic Myopathies

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

SINGLE_GROUP

Primary Study Purpose

BASIC_SCIENCE

Blinding Strategy

NONE

Study Groups

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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.

Group Type EXPERIMENTAL

13C-Glucose Breath Test

Intervention Type DIETARY_SUPPLEMENT

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™)

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).

Group Type EXPERIMENTAL

Doubly labelled water & urine test

Intervention Type DIETARY_SUPPLEMENT

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).

12-week Physiotherapy Intervention

Performed once by all participants, in between the pre- and post-intervention experiments described in the other arms.

Group Type EXPERIMENTAL

12-week Physiotherapy Intervention

Intervention Type OTHER

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.

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).

Group Type EXPERIMENTAL

Clinical Assessments - Exercise Test

Intervention Type DIAGNOSTIC_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).

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).

Group Type EXPERIMENTAL

Clinical Assessment - Muscle Content

Intervention Type DIAGNOSTIC_TEST

Experiment piece 3: Using a well-established clinical method, DXA, once pre and post-intervention to assess for body muscle content (lean muscle mass)

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).

Group Type EXPERIMENTAL

Clinical Assessment - Quality of Life

Intervention Type DIAGNOSTIC_TEST

Experiment piece 3: Using a well-established clinical survey, PedsQL, once pre and post-intervention to assess for participants perception of quality of life.

Interventions

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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.

Intervention Type OTHER

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™)

Intervention Type 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).

Intervention Type DIETARY_SUPPLEMENT

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).

Intervention Type 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)

Intervention Type 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.

Intervention Type DIAGNOSTIC_TEST

Eligibility Criteria

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Inclusion Criteria

* 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.

Exclusion Criteria

* 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.
Minimum Eligible Age

10 Years

Maximum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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University of British Columbia

OTHER

Sponsor Role lead

Responsible Party

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Rajavel Elango, PhD

Principal Investigator

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Rajavel Elango, PhD

Role: PRINCIPAL_INVESTIGATOR

University of British Columbia

Catherine Brunel, MD, FRCPS, FCCMG

Role: PRINCIPAL_INVESTIGATOR

Provincial Health Services Authority British Columbia

Locations

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BC Children's Hospital Research Institute

Vancouver, British Columbia, Canada

Site Status

Countries

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Canada

Other Identifiers

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H20-01177

Identifier Type: -

Identifier Source: org_study_id

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