Glycogen Storage Disease Type VPhase 2NCT02919631
Triheptanoin in Mc Ardle
A Phase 2 study testing Triheptanoin in people with Glycogen Storage Disease Type V, run by Institut National de la Santé Et de la Recherche Médicale, France at 1 site in France.
Trial summary
Background: Patients with the sugar metabolism disorder, Glycogen Storage Disease Type V, have insufficient breakdown of sugar stored as, glycogen, within the cells. The investigators know from previous studies with McArdle patients, that they not only have a reduced sugar metabolism, both also have problems in… Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Glycogen Storage Disease Type V
- What is being tested?
- Triheptanoin
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 12 participants
- Where
- 1 siteFrance
- Study dates
- 16 Nov 2016to 26 Jun 2017
- Phase
- Phase 2
- 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 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Male or female between 18 and 65 years of age,
- Genetically and/or biochemically verified diagnosis of McArdle disease
- Body Mass Index of 18-32
- Women in child-bearing age on contraceptive treatment with: Birth control pills, coil, ring, transdermal hormone patch injection of gestagen or subdermal implant.
- French national health insurance
- Signed informed consent
- Available for phone calls
Who cannot join
- Minor
- Significant cardiac or pulmonary disease
- Pregnancy (confirmed by urinary-HCG) or breastfeeding. Pregnancy not planned and to be avoided during the study by use of effective contraceptive methods.
- Persons deprived of their liberty by judicial or administrative decision
- Adult subject under legal protection or unable to consent
- Treatment with beta-blockers
Show all 9Show fewer
- Inability to perform cycling exercise
- Any other significant disorder that may confound the interpretation of the findings
- Person subject to an exclusion period for a previous clinical trial
Trial locations and contacts
1 site in 1 country.
France1 site
Pitié-Salpêtrière,centre de référence de pathologie neuromusculaire, 47 Bd de l'hôpital
Paris, 75651
About this study
Official title: The Effect of Triheptanoin in Adults With Mc Ardle Disease (Glycogen Storage Disease Type V)
Background: Patients with the sugar metabolism disorder, Glycogen Storage Disease Type V, have insufficient breakdown of sugar stored as, glycogen, within the cells. The investigators know from previous studies with McArdle patients, that they not only have a reduced sugar metabolism, both also have problems in increasing their fat metabolism during exercise to fully compensate for the energy deficiency.
Studies on Triheptanoin diet used in patients with other metabolic diseases have shown that Triheptanoin can increase metabolism of both fat and sugar. In these patients, Triheptanoin has had a positive effect on the physical performance and has reduces the level of symptoms experienced by patients.
Read more
Aim: To investigate the effect of treatment with the dietary oil, Triheptanoin, in patients with McArdle disease on exercise capacity.
Methods: 20-30 adult patients will be recruited through Rigshospitalet in Copenhagen, Denmark and Hopital Pitié-Sapêtrière in Paris, France.
- Pre-experimental testing (1 day): Baseline blood samples are collected to obtain baseline values of safety parameters: Plasma-acylcarnitines, free fatty acids and creatine kinase. Subjects perform a max-test to determine their VO2max
- Treatment period #1 (2 weeks): Subjects follow a diet consuming a dietary treatment oil. Neither patients nor members of the study group know who receive which type of oil.
- Washout period (1 week +7 days): Subjects receive no treatment
- Treatment period #2 (2 weeks +7days): Subjects who received Triheptanoin oil in the first treatment period, now receive placebo oil and vice versa.
Assessments: Before and after each treatment periods, subjects perform a 30-minutes exercise test on a cycle ergometer, comprising of 20-22 minutes of constant load exercise and 6-8 minutes increasing load to peak. Subjects will complete a Fatigue Severity Scale questionnaire and metabolic products will be measured in blood and urine.
Read the detailed description
This project will investigate the treatment potential of the drug Triheptanoin in patients with the inborn defect in glycogen metabolism, McArdle Disease. There is currently no treatment available for this group of patients. The condition leads to intolerance to physical exercise with a risk of developing severe cramps and contractures followed by muscle damage and acute kidney failure. Also one third of the patients develop progressive muscle weakness and wasting.
The McArdle patients have an inherited defect in the enzyme, myofosforylase, an important link in the glycogenolysis within skeletal muscle. As a consequence, the patients lack substrates for glycolysis to fuel muscle work (1). The investigators have previously shown that patients with McArdle disease are unable to increase fat metabolism enough to compensate for the energy insufficiency that occurs in these patients in response to exercise (2).
A key limitation to exercise in McArdle disease is the reduced production of pyruvate, causing depletion of intermediates in the Citric Acid Cycle (CAC). Triheptanoin is a triglyceride of glycerol and three 7-carbon fatty acid chains (heptanoate). The breakdown of odd-number carbon fatty acids, such as heptanoate, generates CAC-intermediates. Triheptanoin can therefore potentially boost the flux through the CAC and increase the ATP and energy generation in the cells.
In other patients with inborn errors of metabolism, treatment with daily Triheptanoin supplement can increase metabolism of both fat and glucose. Triheptanoin treatment has reduced the symptom frequency and increased exercise tolerance and physical performance in these patients (3,4).
The aim of this study is to investigate the effect of Triheptanoin on exercise performance and tolerance and frequency of symptoms in patients with McArdle disease.
METHODS
The study will be designed as a double blinded placebo controlled cross-over study. During a 5 week trial period each study patient will go through a 2 week treatment period, a 1 week (+7days) wash-out period without treatment followed by another 2 week treatment period. In one treatment period, the patient takes a daily dietary oil supplement containing Triheptanoin and in the other period (2 weeks +7days), the oil contains regular safflower oil (placebo). Both Triheptanoin and placebo oil is manufactured, packed and handed out by the manufacturer, Ultragenyx Pharmaceuticals Inc. in a way that neither patients, nor the investigators will know in which period, which treatment is given to which patient.
Assessments:
The patients will meet at the laboratory for assessments on 5 occasions:
Screening visit: Patients perform a peak exercise test on a cycle ergometer wearing a mask that can measure oxygen and carbon dioxide exchange rates. Patients exercise with increasing workload until exhaustion to find their maximal oxidative capacity and maximal workload Test days 1-4: On one test day before and one after each treatment period, the patients perform a 30-minutes exercise test on a cycle ergometer working at a constant moderate intensity for 20-22 minutes followed by a 6-8 minutes stepwise increase to peak workload. Blood samples will be taken before, during and after exercise to measure concentrations of metabolic products. Patients report their current feeling of fatigue in a Fatigue Severity Scale (FSS-questionnaire)
Subjects:
A total number of 21-26 patients will be included in the study across three trial sites. From the French cohort of McArdle Patients; 10-15 patients will be included and from the Danish cohort; 11 patients have been already included.
- Conditions
- Glycogen Storage Disease Type V
- Being tested
- Triheptanoin, Placebo oil
- 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.
TriheptanoinDrug
Also called UX007
Anaplerotic dietary oil
Placebo oilDrug
Also called UX007 Placebo Oral Liquid
Safflower oil
| Study group | Role | What they receive |
|---|---|---|
| triheptanoin | Active comparator | 14 days on Triheptanoin treatment including a 7 days titration period and a 7 days full dose treatment of 1mL/kg/day. Receives: Drug: Triheptanoin |
| placebo oil | Placebo comparator | 14 days of diet on a placebo oil including 7 days titration period and 7 days full dose treatment of 1mL/kg/day Receives: Drug: Placebo oil |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in heart rate during constant load cycling exercise (HRconst) with Triheptanoin vs. placebo treatment.
Subject heart rate will be measured during 20 minutes exercise test performed on a cycle ergometer at a workload corresponding to approximately 60% of maximal oxidative capacity (VO2max).
Measured: Day 14 and Day 28
Secondary outcomes (5)
Change in maximal oxidative capacity (VO2max) with Triheptanoin vs. placebo treatment.
The maximal oxidative capacity measured at peak workload after a 6 minutes ramp test performed on a cycle ergometer after 20 minutes constant load cycling.
Measured: Day 14 and Day 28
Change in self-rated severity of fatigue symptoms with Triheptanoin vs. placebo treatment.
Total score on a Fatigue Severity Scale (FSS)
Measured: Day 14 and 28
Change in urine concentrations of organic acids with Triheptanoin vs. placebo treatment. Urine concentrations of: 3OH-propionate, heptanoate, methylmalonate, pimelate methylcitrate
Measured: Day 14 and 28
Change in maximal workload capacity (Wmax) with Triheptanoin vs. placebo treatment.
The maximal workload capacity (Wmax) is measured at peak workload after a 6 minutes ramp test performed on a cycle ergometer after 20 minutes constant load cycling.
Measured: Day 14 and Day 28
Change in plasma concentrations of metabolites, citric acid cycle (CAC) intermediates with Triheptanoin vs. placebo treatment.
Plasma concentrations of metabolites and citric acid cycle (CAC) intermediates: Lactate, ammonia, glucose, Free Fatty Acids (FFA), acyl-carnitines and malate (a CAC intermediate).
Measured: Day 14 and Day 28
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Sep 2016 (estimated)
- Study start16 Nov 2016
- Primary completion26 Jun 2017
- Study completion26 Jun 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Glycogen Storage Disease Type VStudies of the same condition, open and under way.
- More trials run by Institut National de la Santé Et de la Recherche Médicale, FranceThe 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 12 participants (actual)
Sponsor and investigators
- Sponsor type
- Other government
- Collaborators
- Copenhagen University Hospital, Rigshospitalet
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02919631
- Sponsor's protocol ID
- C15-54
- Status last verified
- Mar 2025
- First submitted
- 28 Sep 2016
- Last updated
- 4 Sep 2025
- Results posted
- No
Publications
Madsen KL, Laforet P, Buch AE, Stemmerik MG, Ottolenghi C, Hatem SN, Raaschou-Pedersen DT, Poulsen NS, Atencio M, Luton MP, Ceccaldi A, Haller RG, Quinlivan R, Mochel F, Vissing J. No effect of triheptanoin on exercise performance in McArdle disease. Ann Clin Transl Neurol. 2019 Oct;6(10):1949-1960. doi: 10.1002/acn3.50863. Epub 2019 Sep 14.
PubMed 31520525
Study at a glance
From the registry record, last updated by the sponsor on 4 Sep 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Effect of Triheptanoin in Adults With Mc Ardle Disease (Glycogen Storage Disease Type V)
- ClinicalTrials.gov ID
- NCT02919631
- Acronym / sponsor ID
- C15-54
- Conditions
- Glycogen Storage Disease Type V
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 12 participants (actual)
- Lead sponsor
- Institut National de la Santé Et de la Recherche Médicale, FranceOther government
- Collaborators
- Copenhagen University Hospital, Rigshospitalet
- Study start
- 16 Nov 2016 (actual)
- Primary completion
- 26 Jun 2017 (actual)
- Study completion
- 26 Jun 2017 (actual)
- First posted
- 29 Sep 2016 (estimated)
- 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.
Background: Patients with the sugar metabolism disorder, Glycogen Storage Disease Type V, have insufficient breakdown of sugar stored as, glycogen, within the cells. The investigators know from previous studies with McArdle patients, that they not only have a reduced sugar metabolism, both also have problems in increasing their fat metabolism during exercise to fully compensate for the energy deficiency.
Studies on Triheptanoin diet used in patients with other metabolic diseases have shown that Triheptanoin can increase metabolism of both fat and sugar. In these patients, Triheptanoin has had a positive effect on the physical performance and has reduces the level of symptoms experienced by patients.
Aim: To investigate the effect of treatment with the dietary oil, Triheptanoin, in patients with McArdle disease on exercise capacity.
Methods: 20-30 adult patients will be recruited through Rigshospitalet in Copenhagen, Denmark and Hopital Pitié-Sapêtrière in Paris, France.
- Pre-experimental testing (1 day): Baseline blood samples are collected to obtain baseline values of safety parameters: Plasma-acylcarnitines, free fatty acids and creatine kinase. Subjects perform a max-test to determine their VO2max
- Treatment period #1 (2 weeks): Subjects follow a diet consuming a dietary treatment oil. Neither patients nor members of the study group know who receive which type of oil.
- Washout period (1 week +7 days): Subjects receive no treatment
- Treatment period #2 (2 weeks +7days): Subjects who received Triheptanoin oil in the first treatment period, now receive placebo oil and vice versa.
Assessments: Before and after each treatment periods, subjects perform a 30-minutes exercise test on a cycle ergometer, comprising of 20-22 minutes of constant load exercise and 6-8 minutes increasing load to peak. Subjects will complete a Fatigue Severity Scale questionnaire and metabolic products will be measured in blood and urine.
Detailed description
This project will investigate the treatment potential of the drug Triheptanoin in patients with the inborn defect in glycogen metabolism, McArdle Disease. There is currently no treatment available for this group of patients. The condition leads to intolerance to physical exercise with a risk of developing severe cramps and contractures followed by muscle damage and acute kidney failure. Also one third of the patients develop progressive muscle weakness and wasting.
The McArdle patients have an inherited defect in the enzyme, myofosforylase, an important link in the glycogenolysis within skeletal muscle. As a consequence, the patients lack substrates for glycolysis to fuel muscle work (1). The investigators have previously shown that patients with McArdle disease are unable to increase fat metabolism enough to compensate for the energy insufficiency that occurs in these patients in response to exercise (2).
A key limitation to exercise in McArdle disease is the reduced production of pyruvate, causing depletion of intermediates in the Citric Acid Cycle (CAC). Triheptanoin is a triglyceride of glycerol and three 7-carbon fatty acid chains (heptanoate). The breakdown of odd-number carbon fatty acids, such as heptanoate, generates CAC-intermediates. Triheptanoin can therefore potentially boost the flux through the CAC and increase the ATP and energy generation in the cells.
In other patients with inborn errors of metabolism, treatment with daily Triheptanoin supplement can increase metabolism of both fat and glucose. Triheptanoin treatment has reduced the symptom frequency and increased exercise tolerance and physical performance in these patients (3,4).
The aim of this study is to investigate the effect of Triheptanoin on exercise performance and tolerance and frequency of symptoms in patients with McArdle disease.
METHODS
The study will be designed as a double blinded placebo controlled cross-over study. During a 5 week trial period each study patient will go through a 2 week treatment period, a 1 week (+7days) wash-out period without treatment followed by another 2 week treatment period. In one treatment period, the patient takes a daily dietary oil supplement containing Triheptanoin and in the other period (2 weeks +7days), the oil contains regular safflower oil (placebo). Both Triheptanoin and placebo oil is manufactured, packed and handed out by the manufacturer, Ultragenyx Pharmaceuticals Inc. in a way that neither patients, nor the investigators will know in which period, which treatment is given to which patient.
Assessments:
The patients will meet at the laboratory for assessments on 5 occasions:
Screening visit: Patients perform a peak exercise test on a cycle ergometer wearing a mask that can measure oxygen and carbon dioxide exchange rates. Patients exercise with increasing workload until exhaustion to find their maximal oxidative capacity and maximal workload Test days 1-4: On one test day before and one after each treatment period, the patients perform a 30-minutes exercise test on a cycle ergometer working at a constant moderate intensity for 20-22 minutes followed by a 6-8 minutes stepwise increase to peak workload. Blood samples will be taken before, during and after exercise to measure concentrations of metabolic products. Patients report their current feeling of fatigue in a Fatigue Severity Scale (FSS-questionnaire)
Subjects:
A total number of 21-26 patients will be included in the study across three trial sites. From the French cohort of McArdle Patients; 10-15 patients will be included and from the Danish cohort; 11 patients have been already included.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| triheptanoin | Active comparator | Drug: Triheptanoin14 days on Triheptanoin treatment including a 7 days titration period and a 7 days full dose treatment of 1mL/kg/day. |
| placebo oil | Placebo comparator | Drug: Placebo oil14 days of diet on a placebo oil including 7 days titration period and 7 days full dose treatment of 1mL/kg/day |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Male or female between 18 and 65 years of age,
- Genetically and/or biochemically verified diagnosis of McArdle disease
- Body Mass Index of 18-32
- Women in child-bearing age on contraceptive treatment with: Birth control pills, coil, ring, transdermal hormone patch injection of gestagen or subdermal implant.
- French national health insurance
Key exclusion criteria (9 listed)
- Minor
- Significant cardiac or pulmonary disease
- Pregnancy (confirmed by urinary-HCG) or breastfeeding. Pregnancy not planned and to be avoided during the study by use of effective contraceptive methods.
- Persons deprived of their liberty by judicial or administrative decision
- Adult subject under legal protection or unable to consent
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 |
|---|---|---|
| TriheptanoinAlso: UX007Anaplerotic dietary oil | Drug | triheptanoin |
| Placebo oilAlso: UX007 Placebo Oral LiquidSafflower oil | Drug | placebo oil |
Primary outcome
Change in heart rate during constant load cycling exercise (HRconst) with Triheptanoin vs. placebo treatment.
Time frame: Day 14 and Day 28
Subject heart rate will be measured during 20 minutes exercise test performed on a cycle ergometer at a workload corresponding to approximately 60% of maximal oxidative capacity (VO2max).
5 secondary outcomes
Change in maximal oxidative capacity (VO2max) with Triheptanoin vs. placebo treatment.
Time frame: Day 14 and Day 28
Change in self-rated severity of fatigue symptoms with Triheptanoin vs. placebo treatment.
Time frame: Day 14 and 28
Change in urine concentrations of organic acids with Triheptanoin vs. placebo treatment. Urine concentrations of: 3OH-propionate, heptanoate, methylmalonate, pimelate methylcitrate
Time frame: Day 14 and 28
Change in maximal workload capacity (Wmax) with Triheptanoin vs. placebo treatment.
Time frame: Day 14 and Day 28
Change in plasma concentrations of metabolites, citric acid cycle (CAC) intermediates with Triheptanoin vs. placebo treatment.
Time frame: Day 14 and Day 28
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 4 Sep 2025.
- Results publication: PubMed 31520525Madsen KL, Laforet P, Buch AE, Stemmerik MG, Ottolenghi C, Hatem SN, Raaschou-Pedersen DT, Poulsen NS, Atencio M, Luton MP, Ceccaldi A, Haller RG, Quinlivan R, Mochel F, Vissing J. No effect of triheptanoin on exercise performance in McArdle disease. Ann Clin Transl Neurol. 2019 Oct;6(10):1949-1960. doi: 10.1002/acn3.50863. Epub 2019 Sep 14.
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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 Phase 2 study testing Triheptanoin in people with Glycogen Storage Disease Type V, run by Institut National de la Santé Et de la Recherche Médicale, France at 1 site in France.
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 7 inclusion and 9 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 4 Sep 2025. 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 France. 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.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
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?
Change in heart rate during constant load cycling exercise (HRconst) with Triheptanoin vs. placebo treatment. (time frame: Day 14 and Day 28). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02919631, which also lists 1 linked publication.
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 4 Sep 2025.