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The Effect of Triheptanoin in Adults With McArdle Disease (Glycogen Storage Disease Type V)

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ClinicalTrials.gov Identifier: NCT02432768
Recruitment Status : Completed
First Posted : May 4, 2015
Last Update Posted : October 16, 2019
Sponsor:
Collaborators:
Groupe Hospitalier Pitie-Salpetriere
University of Texas Southwestern Medical Center
Ultragenyx Pharmaceutical Inc
Information provided by (Responsible Party):
Karen Lindhardt Madsen, Rigshospitalet, Denmark

Brief 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 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, Hopital Pitié-Sapêtrière in Paris, France and through The University of Texas Southwestern Medical Center in Dallas, Texas.

  1. 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

  2. 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.

  3. Washout period (1 week):

    Subjects receive no treatment

  4. Treatment period #2 (2 weeks):

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.


Condition or disease Intervention/treatment Phase
Glycogen Storage Disease Type V Drug: Triheptanoin Other: Placebo oil Phase 2

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 22 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: The Effect of Triheptanoin in Adults With McArdle Disease (Glycogen Storage Disease Type V)
Actual Study Start Date : April 2015
Actual Primary Completion Date : April 2018
Actual Study Completion Date : February 2019


Arm Intervention/treatment
Active Comparator: Triheptanoin
14 days on Triheptanoin treatment including a 7 days titration period and a 7 days full dose treatment of 1mL/kg/day.
Drug: Triheptanoin
Anaplerotic dietary oil
Other Name: UX007

Placebo Comparator: Placebo oil
14 days of diet on a placebo oil including 7 days titration period and 7 days full dose treatment of 1mL/kg/day.
Other: Placebo oil
Safflower oil
Other Name: UX007 Placebo Oral Liquid




Primary Outcome Measures :
  1. 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).


Secondary Outcome Measures :
  1. Change in maximal oxidative capacity (VO2max) with Triheptanoin vs. placebo treatment [ Time Frame: Day 14 and day 28 ]
    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.

  2. Change in self-rated severity of fatigue symptoms with Triheptanoin vs. placebo treatment [ Time Frame: Day 14 and day 28 ]
    Total score on a Fatigue Severity Scale (FSS)

  3. Change in urine concentrations of organic acids with Triheptanoin vs. placebo treatment [ Time Frame: Day 14 and day 28 ]
    Urine concentrations of: 3OH-propionate, heptanoate, methylmalonate, pimelate methylcitrate

  4. Change in maximal workload capacity (Wmax) with Triheptanoin vs. placebo treatment [ Time Frame: Day 14 and day 28 ]
    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.

  5. Change in plasma concentrations of metabolites, citric acid cycle (CAC) intermediates with Triheptanoin vs. placebo treatment [ Time Frame: Day 14 and day 28 ]
    Plasma concentrations of metabolites and citric acid cycle (CAC) intermediates: Lactate, ammonia, glucose, Free Fatty Acids (FFA), acyl-carnitines and malate (a CAC intermediate).



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Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Genetically and/or biochemically verified diagnosis of McArdle disease
  • Body Mass Index of 18-32
  • Capacity to consent

Exclusion Criteria:

  • Significant cardiac and pulmonary disease
  • Pregnancy
  • Treatment with beta-blockers
  • Inability to perform cycling exercise
  • Any other significant disorder that may confound the interpretation of the findings

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02432768


Locations
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Denmark
Copenhagen Neuromuscular Center, 3342, Rigshospitalet
Copenhagen, Denmark, 2100
Sponsors and Collaborators
Rigshospitalet, Denmark
Groupe Hospitalier Pitie-Salpetriere
University of Texas Southwestern Medical Center
Ultragenyx Pharmaceutical Inc
Investigators
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Principal Investigator: Karen L Madsen, MD Neuromuscular Research Unit, Rigshospitalet
Publications:
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Responsible Party: Karen Lindhardt Madsen, MD, Rigshospitalet, Denmark
ClinicalTrials.gov Identifier: NCT02432768    
Other Study ID Numbers: H-8-2014-006
2014-003644-12 ( EudraCT Number )
First Posted: May 4, 2015    Key Record Dates
Last Update Posted: October 16, 2019
Last Verified: October 2019
Keywords provided by Karen Lindhardt Madsen, Rigshospitalet, Denmark:
Anaplerotic diet
McArdle Disease
Glycogen Storage Disease
Triheptanoin
Additional relevant MeSH terms:
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Glycogen Storage Disease
Glycogen Storage Disease Type V
Metabolic Diseases
Disease
Pathologic Processes
Carbohydrate Metabolism, Inborn Errors
Metabolism, Inborn Errors
Genetic Diseases, Inborn