McArdle DiseaseGSDVNCT03945370
Oral Ketone Body Supplementation in Patients With McArdle Disease
A study testing β-hydroxybuturate esters in people with McArdle Disease, run by Copenhagen University Hospital, Rigshospitalet at 1 site in Denmark.
Trial summary
McArdle disease, glycogen storage disease type V, is a rare metabolic disease. Affected individuals are unable to utilize sugar stored as glycogen in muscle. Investigators hypothesize that ketones can be an alternative fuel substrate for skeletal muscle when muscle glycogenolysis is blocked as in McArdle disease. Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- McArdle Disease
- What is being tested?
- β-hydroxybuturate esters
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 8 participants
- Where
- 1 siteDenmark
- Study dates
- 6 May 2019to 1 Oct 2020
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Genetically confirmed McArdle disease or healthy control.
- Patient is willing and able to provide written informed consent prior to participation.
- Patient is ambulatory.
Who cannot join
- Patient has any prior or current medical conditions that, in the judgment of the Investigator, would prevent the patient from safely participating in and/or completing all study requirements.
- Pregnancy or breastfeeding
- Patient does not have the cognitive capacity to understand/comprehend and complete all study assessments.
Trial locations and contacts
1 site in 1 country.
About this study
McArdle disease, glycogen storage disease type V, is a rare metabolic disease. Affected individuals are unable to utilize sugar stored as glycogen in muscle.
Investigators hypothesize that ketones can be an alternative fuel substrate for skeletal muscle when muscle glycogenolysis is blocked as in McArdle disease.
In this study investigators will investigate the immediate effects of an oral supplementation of exogenous ketone bodies (poly-hydroxybuturate) on exercise capacity in patients with metabolic myopathies, compared with a placebo drink.
Read the detailed description
McArdle disease, glycogen storage disease type V, is a rare metabolic disease caused by mutations in the PYGM gene resulting in absence of the enzyme muscle phosphorylase. Affected individuals are unable to utilize sugar stored as glycogen in muscle, leading to exercise intolerance, exercise-induced muscle pain, contractures and rhabdomyolysis, which may cause renal failure. Currently, there are no satisfactory treatment options for McArdle disease.
A key element of alleviating symptoms in McArdle disease is to provide alternative fuels for energy metabolism. Investigators hypothesize that ketones can be an alternative fuel substrate for skeletal muscle when muscle glycogenolysis is blocked as in McArdle disease.
Aim: To investigate the immediate effects of an oral supplementation of exogenous ketone bodies (poly-hydroxybuturate) on exercise capacity in patients with metabolic myopathies.
Supplement description: food supplement containing β-hydroxybuturate esters
Methods:
Study design: Placebo-controlled, single-blind, cross-over study. Inclusion: 5-8 patients with McArdle disease and 3-5 healthy controls.
Time table:
Subjects will meet to 2 test days. Subjects will be randomized using a 1:1 assignment ratio to receive either the keto-drink or placebo drink first. The oral supplement received will be blinded for the participants and the investigators. On each test day, subjects spend approximately 4 hours at the laboratory:
- Insertion of peripheral brachial venous catheters for extracting blood samples and stable isotope infusion and hydroxybutyrate infusion.
- Baseline blood sampling, medical examination, vital sign measurements, weight and height.
- Stable isotope infusion 2 hours before the cycling exercise test. Three stable isotope tracers [2,4-13C2]-D- β-hydroxybutyrate, [1,1,2,3,3-2H5]-glycerol and [6,6-2H2]-glucose solutions, are infused via a venous catheter until a steady-state is reached. The tracer infusions will continue during the cycling test. The tracers (all from Cambridge Isotope Laboratories, Andover, MA, USA) will be dissolved and injected into a solution of 0.9% saline (NaCl) through a bacterial filter.
- One Ketone or placebo drink administration 30 minutes before the exercise test
- Subjects will perform a 40 minutes cycle exercise test at a constant load corresponding to 60-70% of their VO2max (found in a screening study). During the test, subjects wear a mask for continuous gas-exchange measurements and ECG electrodes to determine VO2 and heart rate during constant load cycling (VO2const and HRconst). Blood samples will be drawn 4 times before, every 10 minutes during exercise and after exercise. During the test participants will be asked to rate perceived exertion (RPE) on a Borg scale.
- Conditions
- McArdle Disease
- Being tested
- β-hydroxybuturate esters, Placebo drink
- Medical subject headings
- Glycogen Storage Disease Type V
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
β-hydroxybuturate estersDietary supplement
Oral dietary supplement product containing β-hydroxybuturate esters
Placebo drinkDietary supplement
Oral placebo drink
| Study group | Role | What they receive |
|---|---|---|
| Intervention sequence 1 | Active comparator | Ketone drink first - Placebo drink secondly Receives: Dietary Supplement: β-hydroxybuturate esters; Dietary Supplement: Placebo drink |
| Intervention sequence 2 | Placebo comparator | Placebo drink first - Ketone drink secondly Receives: Dietary Supplement: β-hydroxybuturate esters; Dietary Supplement: Placebo drink |
What is being measured
The primary outcome is the main question the study is designed to answer.
Heart rate
Change between visit 1 and 2 in mean heart rate during constant load cycling exercise (40 minute submaximal cycle test)
Measured: 30 minuts x 2
Secondary outcomes (8)
Ketone metabolism
Change between visit 1 and 2, measured with stable isotope technique during the constant load cycling test
Measured: 150 minuts x 2
Carbohydrate metabolism
Change between visit 1 and 2, measured with stable isotope technique during the constant load cycling test
Measured: 150 minuts x 2
Fat metabolism
Change between visit 1 and 2, measured with stable isotope technique during the constant load cycling test
Measured: 150 minuts x 2
Indirect calorimetry
Changes in oxidation rates at visit 1 and visit 2, measured via indirect calorimetry before and during exercise
Measured: 30 minuts x 2
Perceived exertion
Changes in perceived exertion beween visit 1 and 2 during the cycle test
Measured: 30 minuts x 2
Blood ketone
Changes in ketone bodies in the blood between visit 1 and 2, measured at both before, during and at end exercise.
Measured: 150 minuts x 2
Insulin
Insulin changes between visit 1 and 2 measured before, during and at end exercise.
Measured: 30 minuts x 2
Metabolites
changes between visit 1 and 2
Measured: 30 minuts x 2
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 May 2019
- Study start6 May 2019
- Primary completion1 Oct 2020
- Study completion1 Oct 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for McArdle DiseaseStudies of the same condition, open and under way.
- More trials run by Copenhagen University Hospital, RigshospitaletThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Model description
- Placebo-controlled, single-blind, cross-over study
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 8 participants (actual)
Sponsor and investigators
- Lead sponsor
- Copenhagen University Hospital, Rigshospitalet
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Nicoline Løkken, Copenhagen University Hospital, Rigshospitalet
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03945370
- Sponsor's protocol ID
- H-18033230.1
- Acronym
- GSDV
- Status last verified
- Oct 2020
- First submitted
- 18 Feb 2019
- Last updated
- 6 Oct 2020
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 6 Oct 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Oral Ketone Body Supplementation in Patients With McArdle Disease
- ClinicalTrials.gov ID
- NCT03945370
- Acronym / sponsor ID
- GSDV / H-18033230.1
- Conditions
- McArdle Disease
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 8 participants (actual)
- Lead sponsor
- Copenhagen University Hospital, RigshospitaletUniversity, hospital or other
- Study start
- 6 May 2019 (actual)
- Primary completion
- 1 Oct 2020 (actual)
- Study completion
- 1 Oct 2020 (actual)
- First posted
- 10 May 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
McArdle disease, glycogen storage disease type V, is a rare metabolic disease. Affected individuals are unable to utilize sugar stored as glycogen in muscle.
Investigators hypothesize that ketones can be an alternative fuel substrate for skeletal muscle when muscle glycogenolysis is blocked as in McArdle disease.
In this study investigators will investigate the immediate effects of an oral supplementation of exogenous ketone bodies (poly-hydroxybuturate) on exercise capacity in patients with metabolic myopathies, compared with a placebo drink.
Detailed description
McArdle disease, glycogen storage disease type V, is a rare metabolic disease caused by mutations in the PYGM gene resulting in absence of the enzyme muscle phosphorylase. Affected individuals are unable to utilize sugar stored as glycogen in muscle, leading to exercise intolerance, exercise-induced muscle pain, contractures and rhabdomyolysis, which may cause renal failure. Currently, there are no satisfactory treatment options for McArdle disease.
A key element of alleviating symptoms in McArdle disease is to provide alternative fuels for energy metabolism. Investigators hypothesize that ketones can be an alternative fuel substrate for skeletal muscle when muscle glycogenolysis is blocked as in McArdle disease.
Aim: To investigate the immediate effects of an oral supplementation of exogenous ketone bodies (poly-hydroxybuturate) on exercise capacity in patients with metabolic myopathies.
Supplement description: food supplement containing β-hydroxybuturate esters
Methods:
Study design: Placebo-controlled, single-blind, cross-over study. Inclusion: 5-8 patients with McArdle disease and 3-5 healthy controls.
Time table:
Subjects will meet to 2 test days. Subjects will be randomized using a 1:1 assignment ratio to receive either the keto-drink or placebo drink first. The oral supplement received will be blinded for the participants and the investigators. On each test day, subjects spend approximately 4 hours at the laboratory:
- Insertion of peripheral brachial venous catheters for extracting blood samples and stable isotope infusion and hydroxybutyrate infusion.
- Baseline blood sampling, medical examination, vital sign measurements, weight and height.
- Stable isotope infusion 2 hours before the cycling exercise test. Three stable isotope tracers [2,4-13C2]-D- β-hydroxybutyrate, [1,1,2,3,3-2H5]-glycerol and [6,6-2H2]-glucose solutions, are infused via a venous catheter until a steady-state is reached. The tracer infusions will continue during the cycling test. The tracers (all from Cambridge Isotope Laboratories, Andover, MA, USA) will be dissolved and injected into a solution of 0.9% saline (NaCl) through a bacterial filter.
- One Ketone or placebo drink administration 30 minutes before the exercise test
- Subjects will perform a 40 minutes cycle exercise test at a constant load corresponding to 60-70% of their VO2max (found in a screening study). During the test, subjects wear a mask for continuous gas-exchange measurements and ECG electrodes to determine VO2 and heart rate during constant load cycling (VO2const and HRconst). Blood samples will be drawn 4 times before, every 10 minutes during exercise and after exercise. During the test participants will be asked to rate perceived exertion (RPE) on a Borg scale.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
- Model description
- Placebo-controlled, single-blind, cross-over study
| Arm | Type | Receives |
|---|---|---|
| Intervention sequence 1 | Active comparator | Dietary Supplement: β-hydroxybuturate esters, Dietary Supplement: Placebo drinkKetone drink first - Placebo drink secondly |
| Intervention sequence 2 | Placebo comparator | Dietary Supplement: β-hydroxybuturate esters, Dietary Supplement: Placebo drinkPlacebo drink first - Ketone drink secondly |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Genetically confirmed McArdle disease or healthy control.
- Patient is willing and able to provide written informed consent prior to participation.
- Patient is ambulatory.
Key exclusion criteria (3 listed)
- Patient has any prior or current medical conditions that, in the judgment of the Investigator, would prevent the patient from safely participating in and/or completing all study requirements.
- Pregnancy or breastfeeding
- Patient does not have the cognitive capacity to understand/comprehend and complete all study assessments.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| β-hydroxybuturate estersOral dietary supplement product containing β-hydroxybuturate esters | Dietary supplement | Intervention sequence 1, Intervention sequence 2 |
| Placebo drinkOral placebo drink | Dietary supplement | Intervention sequence 1, Intervention sequence 2 |
Primary outcome
Heart rate
Time frame: 30 minuts x 2
Change between visit 1 and 2 in mean heart rate during constant load cycling exercise (40 minute submaximal cycle test)
8 secondary outcomes
Ketone metabolism
Time frame: 150 minuts x 2
Carbohydrate metabolism
Time frame: 150 minuts x 2
Fat metabolism
Time frame: 150 minuts x 2
Indirect calorimetry
Time frame: 30 minuts x 2
Perceived exertion
Time frame: 30 minuts x 2
Blood ketone
Time frame: 150 minuts x 2
Insulin
Time frame: 30 minuts x 2
Metabolites
Time frame: 30 minuts x 2
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Oct 2020.
- Individual participant dataSharing planned: No
Related trials for McArdle Disease
Active, not recruitingObservational study
Novel Metabolic Muscular Biomarkers in Pompe Disease - a Non-invasive Magnetic Resonance Exploratory Pilot Study.
Pompe Disease, McArdle Disease
Active, not recruitingObservational study
Carbon-13 Magnetic Resonance Spectroscopy in Glycogen Storage Diseases
Glycogen Storage Disease, McArdle Disease
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing β-hydroxybuturate esters in people with McArdle Disease, run by Copenhagen University Hospital, Rigshospitalet at 1 site in Denmark.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 6 Oct 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Denmark. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Heart rate (time frame: 30 minuts x 2). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Oct 2020.