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

NCT02432768 | Completed Phase 2 DMC

• 2 other identifiers: H-8-2014-0062014-003644-12
• Study Type: interventional
• Target: 22
• Locations: 1 country
• Sites: 1

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. 1.Pre-experimental testing (1 day):
2. 2.Treatment period #1 (2 weeks):
3. 3.Washout period (1 week):
4. 4.Treatment period #2 (2 weeks):

Conditions

Glycogen Storage Disease Type V

Keywords

Anaplerotic diet; McArdle Disease; Glycogen Storage Disease; Triheptanoin

Outcome Measures

Primary Outcomes (1)

• 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).

  Day 14 and day 28

Secondary Outcomes (5)

• Change in maximal oxidative capacity (VO2max) with Triheptanoin vs. placebo treatment

  Day 14 and day 28

• Change in self-rated severity of fatigue symptoms with Triheptanoin vs. placebo treatment

  Day 14 and day 28

• Change in urine concentrations of organic acids with Triheptanoin vs. placebo treatment

  Day 14 and day 28

• Change in maximal workload capacity (Wmax) with Triheptanoin vs. placebo treatment

  Day 14 and day 28

• Change in plasma concentrations of metabolites, citric acid cycle (CAC) intermediates with Triheptanoin vs. placebo treatment

  Day 14 and day 28

Study Arms (2)

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.

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.

Other: Placebo oil

Interventions

Triheptanoin DRUG

Anaplerotic dietary oil

Also known as: UX007

Triheptanoin

Placebo oil OTHER

Safflower oil

Also known as: UX007 Placebo Oral Liquid

Placebo oil

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• 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

Sponsors & Collaborators

• Rigshospitalet, Denmark: lead
• Groupe Hospitalier Pitie-Salpetriere: collaborator
• University of Texas Southwestern Medical Center: collaborator
• Ultragenyx Pharmaceutical Inc: collaborator

Study Sites (1)

Copenhagen Neuromuscular Center, 3342, Rigshospitalet

Copenhagen, 2100, Denmark

Location

Related Publications (5)

• Mommaerts WF, Illingworth B, Pearson CM, Guillory RJ, Seraydarian K. A FUNCTIONAL DISORDER OF MUSCLE ASSOCIATED WITH THE ABSENCE OF PHOSPHORYLASE. Proc Natl Acad Sci U S A. 1959 Jun;45(6):791-7. doi: 10.1073/pnas.45.6.791. No abstract available.

  PMID: 16590445 BACKGROUND

• Orngreen MC, Jeppesen TD, Andersen ST, Taivassalo T, Hauerslev S, Preisler N, Haller RG, van Hall G, Vissing J. Fat metabolism during exercise in patients with McArdle disease. Neurology. 2009 Feb 24;72(8):718-24. doi: 10.1212/01.wnl.0000343002.74480.e4.

  PMID: 19237700 BACKGROUND

• Roe CR, Sweetman L, Roe DS, David F, Brunengraber H. Treatment of cardiomyopathy and rhabdomyolysis in long-chain fat oxidation disorders using an anaplerotic odd-chain triglyceride. J Clin Invest. 2002 Jul;110(2):259-69. doi: 10.1172/JCI15311.

  PMID: 12122118 BACKGROUND

• Roe CR, Yang BZ, Brunengraber H, Roe DS, Wallace M, Garritson BK. Carnitine palmitoyltransferase II deficiency: successful anaplerotic diet therapy. Neurology. 2008 Jul 22;71(4):260-4. doi: 10.1212/01.wnl.0000318283.42961.e9.

  PMID: 18645163 BACKGROUND

• Stojkovic T, Vissing J, Petit F, Piraud M, Orngreen MC, Andersen G, Claeys KG, Wary C, Hogrel JY, Laforet P. Muscle glycogenosis due to phosphoglucomutase 1 deficiency. N Engl J Med. 2009 Jul 23;361(4):425-7. doi: 10.1056/NEJMc0901158. No abstract available.

  PMID: 19625727 BACKGROUND

MeSH Terms

Conditions

Glycogen Storage Disease Type V; Glycogen Storage Disease

Interventions

triheptanoin

Condition Hierarchy (Ancestors)

Carbohydrate Metabolism, Inborn Errors; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Metabolic Diseases; Nutritional and Metabolic Diseases

Study Officials

• Karen L Madsen, MD

  Neuromuscular Research Unit, Rigshospitalet

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD

Study Record Dates

• First Submitted: November 4, 2014
• First Posted: May 4, 2015
• Study Start: April 1, 2015
• Primary Completion: April 1, 2018
• Study Completion: February 1, 2019
• Last Updated: October 16, 2019

Record last verified: 2019-10

Locations

DK (1)