GDF-15 as a Biomarker for Mitochondrial Disease

NCT02745938 | Completed DMC

• 1 other identifier: H-16023953
• Study Type: observational
• Target: 97
• Locations: 1 country
• Sites: 1

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.

Conditions

Mitochondrial Disease; Metabolic Myopathy; Muscular Dystrophy

Keywords

Exercise test; GDF-15; Growth and Differentiation Factor 15

Outcome Measures

Primary Outcomes (1)

• GDF-15 concentration in plasma sample at rest.

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

  One blood sample per subject will be analysed. It takes 5 minutes.

Secondary Outcomes (7)

• GDF-15 concentration in plasma after exercise

  The exercise test takes half an hour. Blood samples will be taken 1, 2, 3, 24 and 48 hours after the exercise test.

• Other biomarkers of energy metabolism disorders at rest and after exercise test.

  If the blood samples are only taken at rest, the test takes 5 minutes. If an exercise test is done, it takes 48 hours.

• Other biomarkers of energy metabolism disorders at rest and after exercise test.

  If the blood samples are only taken at rest, the test takes 5 minutes. If an exercise test is done, it takes 48 hours.

• Other biomarkers of energy metabolism disorders at rest and after exercise test.

  If the blood samples are only taken at rest, the test takes 5 minutes. If an exercise test is done, it takes 48 hours.

• Other biomarkers of energy metabolism disorders at rest and after exercise test.

  If the blood samples are only taken at rest, the test takes 5 minutes. If an exercise test is done, it takes 48 hours.

Study Arms (4)

Mitochondrial disease

Patients with mitochondrial disease, investigated by blood samples and exercise test.

Metabolic myopathy

Patients with metabolic myopathy, investigated by blood samples and exercise test.

Muscular dystrophy

Patients with muscular dystrophy, investigated by blood samples and exercise test.

Healthy controls

Healthy controls, investigated by blood samples and exercise test.

Eligibility Criteria

• Age: 15 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Four groups are studied: 1. Patients with mitochondrial disease. 2. Patients with metabolic myopathy. 3. Patients with muscular dystrophy. 4. Healthy controls.

You may qualify if:

• Verified mitochondrial disease, metabolic myopathy or muscular dystrophy.

You may not qualify if:

• Other muscle disorders.
• Heart failure or significantly reduced kidney or lung function.
• Contraindications for exercise test, e.g. serious heart and lung disease. The investigator will decide whether or not it is possible for the subject to participate (Only for the subjects doing an exercise test.).
• Criteria for healthy individuals:
• None (except age \> 15 years).
• Any muscle disorder
• Heart failure
• Contraindications for exercise test, e.g. serious heart and lung disease. The investigator will decide whether or not it is possible for the subject to participate (Only when participating in the exercise test).

Sponsors & Collaborators

• Rigshospitalet, Denmark: lead

Study Sites (1)

Rigshospitalet

Copenhagen, Copenhagen East., 2100, Denmark

Location

Related Publications (6)

• Sharp LJ, Haller RG. Metabolic and mitochondrial myopathies. Neurol Clin. 2014 Aug;32(3):777-99, ix. doi: 10.1016/j.ncl.2014.05.001.

  PMID: 25037090 BACKGROUND

• Lightowlers RN, Taylor RW, Turnbull DM. Mutations causing mitochondrial disease: What is new and what challenges remain? Science. 2015 Sep 25;349(6255):1494-9. doi: 10.1126/science.aac7516. Epub 2015 Sep 24.

  PMID: 26404827 BACKGROUND

• Yatsuga S, Fujita Y, Ishii A, Fukumoto Y, Arahata H, Kakuma T, Kojima T, Ito M, Tanaka M, Saiki R, Koga Y. Growth differentiation factor 15 as a useful biomarker for mitochondrial disorders. Ann Neurol. 2015 Nov;78(5):814-23. doi: 10.1002/ana.24506. Epub 2015 Oct 14.

  PMID: 26463265 BACKGROUND

• Kalko SG, Paco S, Jou C, Rodriguez MA, Meznaric M, Rogac M, Jekovec-Vrhovsek M, Sciacco M, Moggio M, Fagiolari G, De Paepe B, De Meirleir L, Ferrer I, Roig-Quilis M, Munell F, Montoya J, Lopez-Gallardo E, Ruiz-Pesini E, Artuch R, Montero R, Torner F, Nascimento A, Ortez C, Colomer J, Jimenez-Mallebrera C. Transcriptomic profiling of TK2 deficient human skeletal muscle suggests a role for the p53 signalling pathway and identifies growth and differentiation factor-15 as a potential novel biomarker for mitochondrial myopathies. BMC Genomics. 2014 Feb 1;15:91. doi: 10.1186/1471-2164-15-91.

  PMID: 24484525 BACKGROUND

• Kitaoka Y, Ogborn DI, Nilsson MI, Mocellin NJ, MacNeil LG, Tarnopolsky MA. Oxidative stress and Nrf2 signaling in McArdle disease. Mol Genet Metab. 2013 Nov;110(3):297-302. doi: 10.1016/j.ymgme.2013.06.022. Epub 2013 Jul 6.

  PMID: 23906480 BACKGROUND

• Suomalainen A, Elo JM, Pietilainen KH, Hakonen AH, Sevastianova K, Korpela M, Isohanni P, Marjavaara SK, Tyni T, Kiuru-Enari S, Pihko H, Darin N, Ounap K, Kluijtmans LA, Paetau A, Buzkova J, Bindoff LA, Annunen-Rasila J, Uusimaa J, Rissanen A, Yki-Jarvinen H, Hirano M, Tulinius M, Smeitink J, Tyynismaa H. FGF-21 as a biomarker for muscle-manifesting mitochondrial respiratory chain deficiencies: a diagnostic study. Lancet Neurol. 2011 Sep;10(9):806-18. doi: 10.1016/S1474-4422(11)70155-7. Epub 2011 Aug 3.

  PMID: 21820356 BACKGROUND

Biospecimen

Retention: SAMPLES WITH DNA

Blood samples

MeSH Terms

Conditions

Mitochondrial Diseases; Muscular Dystrophies

Condition Hierarchy (Ancestors)

Metabolic Diseases; Nutritional and Metabolic Diseases; Muscular Disorders, Atrophic; Muscular Diseases; Musculoskeletal Diseases; Neuromuscular Diseases; Nervous System Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Study Officials

• Nanna S. Nielsen, B.Sc.

  Copenhagen Neuromuscular Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: CROSS SECTIONAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Student researcher

Study Record Dates

• First Submitted: April 12, 2016
• First Posted: April 20, 2016
• Study Start: June 1, 2016
• Primary Completion: August 1, 2017
• Study Completion: August 1, 2017
• Last Updated: August 17, 2017

Record last verified: 2017-08

Data Sharing

• IPD Sharing: Will not share

Locations

DK (1)