Top

Published in:

Open Access 01-11-2018 | Original Article

Outcome measures for children with mitochondrial disease: consensus recommendations for future studies from a Delphi-based international workshop

Authors: Saskia Koene, Lara van Bon, Enrico Bertini, Cecilia Jimenez-Moreno, Lianne van der Giessen, Imelda de Groot, Robert McFarland, Sumit Parikh, Shamima Rahman, Michelle Wood, Jiri Zeman, Anjo Janssen, Jan Smeitink

Published in: Journal of Inherited Metabolic Disease | Issue 6/2018

Abstract

Although there are no effective disease-modifying therapies for mitochondrial diseases, an increasing number of trials are being conducted in this rare disease group. The use of sensitive and valid endpoints is essential to test the effectiveness of potential treatments. There is no consensus on which outcome measures to use in children with mitochondrial disease. The aims of this two-day Delphi-based workshop were to (i) define the protocol for an international, multi-centre natural history study in children with mitochondrial myopathy and (ii) to select appropriate outcome measures for a validation study in children with mitochondrial encephalopathy. We suggest two sets of outcome measures for a natural history study in children with mitochondrial myopathy and for a proposed validation study in children with mitochondrial encephalopathy.

Casey AF, Wang X, Osterling K (2012) Test–retest reliability of the 6-minute walk test in individuals with Down syndrome. Arch Phys Med Rehabil 93:2068–2074CrossRefPubMed

Chinnery PF, Turnbull DM (2001) Epidemiology and treatment of mitochondrial disorders. Am J Med Genet 106:94–101CrossRefPubMed

Cox GF (2018) The art and science of choosing efficacy endpoints for rare disease clinical trials. Am J Med Genet A 176:759–772CrossRefPubMed

de Laat P, Koene S, van den Heuvel LP, Rodenburg RJ, Janssen MC, Smeitink JA (2012) Clinical features and heteroplasmy in blood, urine and saliva in 34 Dutch families carrying the m.3243A > G mutation. J Inherit Metab Dis 35:1059–1069CrossRefPubMedPubMedCentral

Debray FG, Lambert M, Chevalier I et al (2007) Long-term outcome and clinical spectrum of 73 pediatric patients with mitochondrial diseases. Pediatrics 119:722–733CrossRefPubMed

Food and Drug Administration (2009) Guidance for industry: patient-reported outcome measures: use in medical product development to support labeling claims. U.S. Department of Health and Human Services

Gorman GS, Chinnery PF, DiMauro S et al (2016) Mitochondrial diseases. Nat Rev Dis Primers 2:16080CrossRef

Jorm AF (2015) Using the Delphi expert consensus method in mental health research. Aust N Z J Psychiatry 49:887–897CrossRefPubMed

Keshavan NRS (2018) Natural history of mitochondrial disorders: a systematic review. Essays Biochem (in press)

Koene S, Kozicz TL, Rodenburg RJ et al (2009) Major depression in adolescent children consecutively diagnosed with mitochondrial disorder. J Affect Disord 114:327–332CrossRefPubMed

Koene S, Jansen M, Verhaak CM, De Vrueh RL, De Groot IJ, Smeitink JA (2013) Towards the harmonization of outcome measures in children with mitochondrial disorders. Dev Med Child Neurol 55:698–706PubMed

Koopman WJ, Beyrath J, Fung CW et al (2016) Mitochondrial disorders in children: toward development of small-molecule treatment strategies. EMBO Mol Med 8:311–327CrossRefPubMedPubMedCentral

Leonard JV, Schapira AH (2000a) Mitochondrial respiratory chain disorders I: mitochondrial DNA defects. Lancet 355:299–304CrossRefPubMed

Leonard JV, Schapira AH (2000b) Mitochondrial respiratory chain disorders II: neurodegenerative disorders and nuclear gene defects. Lancet 355:389–394CrossRefPubMed

Mancuso M, McFarland R, Klopstock T, Hirano M; consortium on Trial Readiness in Mitochondrial Myopathies (2017) International workshop:: outcome measures and clinical trial readiness in primary mitochondrial myopathies in children and adults. Consensus recommendations. 16–18 November 2016, Rome, Italy. Neuromuscul Disord 27:1126–1137CrossRefPubMedPubMedCentral

Pfeffer G, Horvath R, Klopstock T et al (2013) New treatments for mitochondrial disease-no time to drop our standards. Nat Rev Neurol 9:474–481CrossRefPubMedPubMedCentral

Rahman J, Rahman S (2018) Mitochondrial medicine in the omics era. Lancet. pii: S0140-6736(18)30727-X

Schaefer AM, McFarland R, Blakely EL et al (2008) Prevalence of mitochondrial DNA disease in adults. Ann Neurol 63:35–39CrossRefPubMed

Schuller Y, Hollak CEM, Gispen-de Wied CC, Stoyanova-Beninska V, Biegstraaten M (2017) Factors contributing to the efficacy–effectiveness gap in the case of orphan drugs for metabolic diseases. Drugs 77:1461–1472CrossRefPubMedPubMedCentral

Skladal D, Sudmeier C, Konstantopoulou V et al (2003) The clinical spectrum of mitochondrial disease in 75 pediatric patients. Clin Pediatr (Phila) 42:703–710CrossRef

Valanne L, Ketonen L, Majander A, Suomalainen A, Pihko H (1998) Neuroradiologic findings in children with mitochondrial disorders. AJNR Am J Neuroradiol 19:369–377PubMed

Viscomi C (2016) Toward a therapy for mitochondrial disease. Biochem Soc Trans 44:1483–1490CrossRefPubMedPubMedCentral

Title: Outcome measures for children with mitochondrial disease: consensus recommendations for future studies from a Delphi-based international workshop
Authors: Saskia Koene
Lara van Bon
Enrico Bertini
Cecilia Jimenez-Moreno
Lianne van der Giessen
Imelda de Groot
Robert McFarland
Sumit Parikh
Shamima Rahman
Michelle Wood
Jiri Zeman
Anjo Janssen
Jan Smeitink
Publication date: 01-11-2018
Publisher: Springer Netherlands
Published in: Journal of Inherited Metabolic Disease / Issue 6/2018
Print ISSN: 0141-8955
Electronic ISSN: 1573-2665
DOI: https://doi.org/10.1007/s10545-018-0229-5

ACC 2024 Congress Coverage

Heart Failure Video

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Outcome measures for children with mitochondrial disease: consensus recommendations for future studies from a Delphi-based international workshop

Abstract

ACC 2024 Congress Coverage

Year in Review: Heart failure and cardiomyopathies

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

Incentivised to exercise

New intervention for STEMI-related cardiogenic shock

» View more highlights on the ACC 2024 congress hub page

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Abstract

Please log in to get access to this content

Other articles of this Issue 6/2018

Correction to: Medical and financial burden of acute intermittent porphyria

Postsynaptic movement disorders: clinical phenotypes, genotypes, and disease mechanisms

Induced pluripotent stem cells (iPSCs) as model to study inherited defects of neurotransmission in inborn errors of metabolism

The efficacy of intracerebroventricular idursulfase-beta enzyme replacement therapy in mucopolysaccharidosis II murine model: heparan sulfate in cerebrospinal fluid as a clinical biomarker of neuropathology

Molecular biology and gene therapy for glycogen storage disease type Ib

Next-generation glycogen storage diseases

ACC 2024 Congress Coverage

Year in Review: Heart failure and cardiomyopathies

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

Incentivised to exercise

New intervention for STEMI-related cardiogenic shock

» View more highlights on the ACC 2024 congress hub page