Clinical Trial: GDF-15 as a Biomarker for Mitochondrial Disease

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Observational

Official Title: GDF-15 as a Biomarker for Mitochondrial Disease

Brief Summary:

Mitochondrial disorders are a group of inherited disorders causing malfunctional mitochondria. Mitochondria are found in every cell of the body, and the disorders therefore give symptoms from every tissue, especially those with high energy needs as the brain, heart and muscles. The symptoms are often unspecific in terms of muscle weakness and fatigue, which delays the first contact to the doctor and further delays the diagnosis.

The aim of this study is to investigate if it is possible to use GDF-15 (Growth and Differentiation Factor 15) as a biomarker for mitochondrial disease and compare the results with that of healthy controls, metabolic myopathies and muscular dystrophies. The concentration relative to exercise will further be investigated.


Detailed Summary:

BACKGROUND

Energy insufficiency:

Mitochondrial and metabolic myopathies are inherited diseases compromising cellular energy metabolism, which especially affects skeletal muscle because of its high energy needs. Chemical energy is stored in the body as adenosine triphosphate (ATP), which is derived from different sources including breakdown of carbohydrates, lipids and purine nucleotides. In the respiratory chain in the inner mitochondrial membrane, ATP is released through oxidative phosphorylation.

Any genetic disorder affecting any step in the production of energy, from storage and breakdown of glycogen and lipids to transport and conversion of substrates, can manifest as energy insufficiency in the affected tissues.

Mutations in genes encoding enzymes of the lipid or carbohydrate metabolism result in metabolic myopathies and mutations in the enzyme complexes of the respiratory chain result in mitochondrial disorders.

Mitochondrial disorders:

Mitochondrial disorders are caused by mutations in either mitochondrial DNA (mtDNA) or nuclear DNA (nDNA) which lead to impaired function of the respiratory chain and reduced energy generation. The disorders derived from mtDNA mutations are maternally inherited, while the nDNA mutations are autosomal recessively or dominantly inherited.

Mitochondrial disorders present with a wide range of symptoms and syndromes depending on the mutation and mutation load in tissues. Symptoms usually arise from the brain, nerves, skeletal and cardiac muscle, as these tissues have a high energy demand. The patients may suffer from muscle weakness, exercise
Sponsor: Rigshospitalet, Denmark

Current Primary Outcome: GDF-15 concentration in plasma sample at rest. [ Time Frame: One blood sample per subject will be analysed. It takes 5 minutes. ]

The blood sample will be analysed with a Luminex analyser to determine the concentration of GDF-15.


Original Primary Outcome: Same as current

Current Secondary Outcome:

  • GDF-15 concentration in plasma after exercise [ Time Frame: The exercise test takes half an hour. Blood samples will be taken 1, 2, 3, 24 and 48 hours after the exercise test. ]
    The subjects perform an incremental exercise test until exhaustion on a cycle ergometer. The concentration of GDF-15 is measured afterwards with a Luminex analyser.
  • Other biomarkers of energy metabolism disorders at rest and after exercise test. [ Time Frame: If the blood samples are only taken at rest, the test takes 5 minutes. If an exercise test is done, it takes 48 hours. ]
    Lactate is a muscle marker, that is measured in this study.
  • Other biomarkers of energy metabolism disorders at rest and after exercise test. [ Time Frame: If the blood samples are only taken at rest, the test takes 5 minutes. If an exercise test is done, it takes 48 hours. ]
    Pyruvate is a muscle marker, that is measured in this study.
  • Other biomarkers of energy metabolism disorders at rest and after exercise test. [ Time Frame: If the blood samples are only taken at rest, the test takes 5 minutes. If an exercise test is done, it takes 48 hours. ]
    Creatin kinase is a muscle marker, that is measured in this study.
  • Other biomarkers of energy metabolism disorders at rest and after exercise test. [ Time Frame: If the blood samples are only taken at rest, the test takes 5 minutes. If an exercise test is done, it takes 48 hours. ]
    FGF-21 (Fibroblast Growth Factor 21) is a muscle marker that is measured in this study.
  • Maximal oxidative capacity (VO2max) [ Time Frame: The test takes half an hour per subject. ]
    During the exercise test, the subjects will breath through a mask, that is connected to a machine. The machine is able to calculate the VO2max.
  • Maximal workload capacity (Wmax) [ Time Frame: The test takes half an hour per subject. ]
    The Wmax will be calculated during the exercise test.


Original Secondary Outcome: Same as current

Information By: Rigshospitalet, Denmark

Dates:
Date Received: April 12, 2016
Date Started: June 2016
Date Completion: January 2018
Last Updated: July 4, 2016
Last Verified: July 2016