Abstract
Feasible, sensitive and clinically relevant outcome measures are of extreme importance when designing clinical trials. For paediatric mitochondrial disease, no robust end point has been described to date. The aim of this study was to select the domains of daily physical activity, which can be measured by 3D accelerometry, that could serve as sensitive end points in future clinical trials in children with mitochondrial disorders.
In this exploratory observational study, 17 patients with mitochondrial disease and 16 age- and sex-matched controls wore 3D accelerometers at the upper leg, upper arm, lower arm and chest during one weekend. Using the raw data obtained by the accelerometers, we calculated the following outcome measures: (1) average amount of counts per hour the sensors were worn; (2) the maximal intensity; (3) the largest area under the curve during 30 min and (4) categorized activities lying, standing or being dynamically active. Measuring physical activity during the whole weekend was practically feasible in all participants. We found good face validity by visually correlating the validation videos and activity diaries to the accelerometer data-graphs. Patients with mitochondrial disorders had significantly lower peak intensity and were resting more, compared to their age- and sex-matched peers.
Finally, we suggest domains of physical activity that could be included when measuring daily physical activity in children with mitochondrial disorders, preferably using more user-friendly devices. These include peak activity parameters for the arms (all patients) and legs (ambulatory patients). We recommend using or developing devices that measure these domains of physical activity in future clinical studies.
Ilse Dirks and Esmee van Mierlo contributed equally to this work.
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Communicated by: Shamima Rahman, FRCP, FRCPCH, PhD
Electronic Supplementary Material
Supplementary Table 1
Characteristics of patients and their age- and sex-matched controls. A level of p = 0.05 was used for significance; significant values are indicated in bold; BMI Body Mass Index (XLSX 13 kb)
Supplementary Table 2
Patient characteristics. Genetic, biochemical and clinical details for each patient. Psychomotor retardation is defined: IQ <50 = severe; IQ 50–70 = mild and IQ >70 = normal. 1 = genetically confirmed primary mitochondrial disease; 2 = genetically confirmed secondary mitochondrial disease; 3 = biochemically confirmed mitochondrial dysfunction. # siblings, A ankle, CI complex I, F female, GMFM gross motor function measure, L leukocytes, M male, Mu muscle, ND not done, PEDI pediatric evaluation of disability inventory, PMR psychomotor retardation, UEC urinary epithelial cells (XLSX 14 kb)
Supplementary Table 3
Correlations between the GMFM and the PEDI and activity parameters measured with the accelerometer. A level of p = 0.001 was used for significance; significant values are indicated in bold; AUC area under the curve, GMFM gross motor function measure, PEDI pediatric evaluation of disability inventory (XLSX 9 kb)
Supplementary Fig. 1
Percentage of rest during the weekend for patients versus matched controls. The dark bars represent the patients and the light bars represent their matched controls. Group 1 = genetically confirmed primary mitochondrial disease; group 2 = genetically confirmed secondary mitochondrial disease; group 3 = biochemically confirmed mitochondrial dysfunction (PNG 10 kb)
Take Home Message
Take Home Message
Children with mitochondrial disorders have lower peak activity rather than a lower amount activity compared to healthy peers.
Details of the Contributions of Individual Authors
Saskia Koene | Planning, supervising and reporting of study |
Ilse Dirks | Execution and planning of study, critical review manuscript |
Esmee van Mierlo | Execution of study, critical review manuscript |
Pascal de Vries | Analysis of data, critical review manuscript |
Anjo J. W. M. Janssen | Performance physiotherapeutic tests, critical review manuscript |
Jan A. M. Smeitink | Supervision of study, critical review manuscript |
Arjen Bergsma | Data analysis, critical review manuscript |
Hans Essers | Data analysis, critical review manuscript |
Kenneth Meijer | Critical review manuscript |
Imelda J. M. de Groot | Supervision of planning of study, critical review manuscript |
Name of One Author Who Serves as Guarantor
Saskia Koene.
A Competing Interest Statement
Imelda J. M. de Groot is consultant for Biomarin, PTC, Treat-NMD. She has collaborations in scientific projects on the development of technical aids (arm and hand exoskeletons) with Focal Meditech, Hankamp, BAAT Medical products, Summit, Laevo, Xsens, Maastricht Instruments. She has no financial interest in these firms. Jan Smeitink is the founding CEO of Khondrion BV.
Details of Funding
We thank all patients and parents participating in this study. This project was sponsored by Stofwisselkracht, Zeldzame Ziekten Fonds and ZonMW (The Netherlands Organization for Health Research and Development). The author(s) confirm(s) independence from the sponsors; the content of the article has not been influenced by the sponsors.
Details of Ethics Approval/A Patient Consent Statement
This study was approved by the regional Medical Research Ethics Committee (MREC NL50560.091.14). In accordance with the Helsinki agreement, written informed consent was obtained from participant’s legal guardian and, where indicated, the participant.
Approval from the Institutional Committee for Care and Use of Laboratory Animals
Not indicated.
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Koene, S. et al. (2017). Domains of Daily Physical Activity in Children with Mitochondrial Disease: A 3D Accelerometry Approach. In: Morava, E., Baumgartner, M., Patterson, M., Rahman, S., Zschocke, J., Peters, V. (eds) JIMD Reports, Volume 36. JIMD Reports, vol 36. Springer, Berlin, Heidelberg. https://doi.org/10.1007/8904_2016_35
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DOI: https://doi.org/10.1007/8904_2016_35
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