KETOMY: trail, Safety, efficacy and feasibility of ketogenic diet in mitochondrial myopathy,

Mitochondrial myopathy is a common presentation of mitochondrial disease, for
which there is no curative therapy. Diet could be an important disease modifier
in these patients, since it provides the essential nutrients for mitochondria
to produce energy. Ketogenic diet has been proven effective to treat
intractable epilepsy in children with or without a mitochondrial disease. In
cell studies and mice models for mitochondrial myopathy, ketone bodies or
ketogenic diets significantly improve mitochondrial function and delay disease
progression. The hypothesis is that because of heterogenicity in MD not al MD
patients will respond in the same way to the MAD intervention.
Ketogenic diets can cause side effects, such as headaches, fatigue, weight
loss, nausea, and gastro-intestinal symptoms. More recently, a study in five
patients with a mitochondrial myopathy showed muscle damage and increased
muscle pain after two weeks modified Atkins diet (mAD) as a potential
additional serious adverse event.

Objective: Our proposed pilot study explores the safety, feasibility and
efficacy of ketogenic diet in adults with mitochondrial myopathy to improve
exercise intolerence and look for biomarkers that might predict patient
response to the MAD intervention..

Study design: controlled trial, one armed intervention, pilot study healthy
controls just voor metabolomics

Modified Atkins diet

During the complete study period, patients are asked for a hospital visit six
times, of which three will include a maximal incremental cycling test, muscle
strength test and physical examination including body composition
measurements. The questionnaires and body composition test are non-invasive
but the cycling test can be burdensome for patients with a mitochondrial
disease who experience exercise intolerance in daily life. Blood sampling: a
venous blood sample will be drawn an screening and at every hospital visit
(seven times in total). At home, fingerprick blood sampling to control glucose
level will be performed by the participant 25 times. At home, a three-day food
diary has to be filled in eight times during the study course. An
accelerometer, as an activity tracker, has to be worn four times during the
study duration and a headache diary has to be filled in whenever such an event
occurs. Side effects are scored at every visit or if such an event occurs in
between. The diet itself can be a burden because patients are very much
restricted in carbohydrates (e.g. the patients cannot eat comfort food or
sweets) for 12 weeks. This is difficult for most patients especially in social
situations but they also have to cook and shop different products from their
normal eating pattern. Last burden for the participants is that the diet might
have side effects. Mild side effects especially in the beginning of the diet
are known like gastro- intestinal discomfort (constipation and nausea),
fatigue, headage and flu-like symptoms (*keto-flu*). These symptoms are usually
mild and can be treated with fine tuning of the diet. A more severe possible
side effect is muscle pain that is rare in our experience and will be monitored
closely in this study.
Blood test for lipids glucose and body composition measurements are preferably
done in a fasting state in the morning. So 3 out of 6 hospital visit need to
be in de morning after an overnight fast.

Patient on a ketogenic diet usually lose weight and this can be both a risk as
a benefit for patients depending on their nutritional status. The study can
give them other benefits as well: it might give them more energy, and improve
their exercise intolerance. Ketogenic diet might also improve their migraine,
if present. The diet gives participants an opportunity to help find possible
new treatment options for this progressive disease wherefor until now treatment
options are scarce. It also gives them the means to possible help themselves.
Ketogenic diet is commonly discussed and advised in lay-literature and social
platforms and we get plenty of questions from patients who want to try it. This
study gives them to opportunity to do so in a safe and controlled manner.
Because of the weight loss, the lipid profile and cardiovascular risk can
improve but on the other hand hyperlipemia as a side effect of ketogenic diet
has also been reported.

healthy controls minor risk only midl side effects are espected like gastro
intestinal burden