Selecting Outcome measures for MITOchondrial disease in children: an explorative study

For clinical trials, it is of great importance to select clinically relevant,
feasible, reliable and valid instruments to measure disease progression. To
date, there is no experience or information on which instruments to use in
children with mitochondrial disorders. Previously, we selected 33 clinically
relevant and scientifically robust instruments based on an extensive literature
search. Besides, several instruments for paediatric mitochondrial disease have
been developed. In this study we aim to obtain more knowledge about the value
of these instruments in measuring disease severity and progression in children
with mitochondrial disease with the final aim to provide more information on
these instruments to be used in future drug intervention clinical trial.

To study feasibility, reliability and validity of a specific set of outcome
measures in children with mitochondrial myopathy.

The study is a longitudinal observational study, in which patients are seen at
time x, time x + 2 weeks (retest) and time x * 2 weeks (training). The patients
will be seen by two experienced assessors, who will both keep their own CRF.
The examinations will be videotaped and, where possible, be scored again after
4 weeks to determine inter-rater reliability. Since mitochondrial disorders,
are rare, we use a multi-centre design (for recruitment only).

This protocol was supported by three different patients organizations,
underlining the need for reliable outcome measures also from a patient
perspective. Patients will be seen at the outpatient clinic of the
Rehabilitation department three times. This means that they will not be able to
attend day-care, kindergarden, or school during that time. They will be asked
to perform several tests, which are regularly used to follow the functional
capacities of handicapped children. Most children will be familiar with these
kinds of test from their daily (rehabilitation) care. All tests measure daily
functional capacities, none of the tests alone will be too tiring, though since
these patients have a mitochondrial disorder and are easily tired, it is
possible that the total day of testing will be tiring. To minimize this, we
created a balanced programme with regular pauses, which in our previous
experiences is not too burdensome to the patient. The programme was checked by
a child with mitochondrial myopathy and estimated to be feasible. Also, it is
known that some patients with mitochondrial disease may suffer from muscle pain
after light exercise. The risks of a serious complication of the individual
tests are however, both in literature and in our experience, negligible.
Since we aim to test paediatric measurement instruments, this study cannot be
performed in adults. We think this study will be relevant not only for children
with mitochondrial myopathies, but also for other paediatric and adult
mitochondrial diseases, since using feasible, reliable and valid instruments
increases the likelihood that relevant and valid conclusions will be drawn on
the effect of future treatments.