Acute Nutritional Ketosis in VLCAD Deficiency: Testing the Metabolic Base for Therapeutic Use
To test if a ketone-ester based drink can boost muscle mitochondrial function in vivo in
patients with VLCADD in order to establish a rational basis for therapeutic use in this
Exertional rhabdomyolysis is a common symptom in very long-chain acylCoA dehydrogenase
deficient (VLCADD) patients. Failing muscle ATP homeostasis, due to impaired fatty acid
oxidation, is the most likely cause. Therefore, supplementation with an alternative energy
substrate to boost ATP homeostasis, such as an exogenous ketone ester (KE) drink, could be a
therapeutic option. Previous results suggest that KE is preferentially oxidized in the
tricyclic acid (TCA) cycle and improves physical endurance in athletes. Our primary objective
is to test if KE boosts muscular ATP homeostasis in VLCADD patients to establish a rational
basis for therapeutic use.
VLCADD patients will be included in a randomized, blinded, placebo controlled, 2-way
cross-over trial. Prior to each test, patients receive a KE drink or an isocaloric
carbohydrate equivalent, and completed a 35 min cycling test on an upright bicycle, followed
by 10 minutes of supine cycling inside a MR scanner. The protocol will be repeated after at
least one week with the opposite drink.
Change of ATP concentration in millimolar
kinetic rate constant of ATP synthesis in Hertz
ketone ester drink
Study Arms / Comparison Groups
ketone ester drink
Description: Oral intake of ketone ester drink muscle biopsy exercise muscle biopsy Magnetic Resonance imaging
* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.
April 1, 2016
April 1, 2017
Primary Completion Date
March 31, 2017
- Confirmed VLCADD by genetic profiling
- contraindications for MRI studies (assessed by standardised questionnaire as
previously used in METC 08-267/K; see UMCG section F METC documents)
- inability to perform bicycle exercise.
- recent episode of rhabdomyolysis, or treatment for acute renal failure in the past 2
- intercurrent illness which may influence exercise tolerance (anaemia, musculoskeletal
injury, or other undiagnosed illness under investigation).
- known coronary artery disease, positive history for angina, or changes on ECG
suggestive of previous ischaemia without a negative stress test.
- insulin-dependent diabetes mellitus.
- loss of, or an inability to give informed consent.
- pregnancy or current breastfeeding, or females not taking the oral contraceptive pill
(this is due to the variability in hormonal patterns and substrate levels with
different parts of the menstrual cycle).
- any other cause which in the opinion of the investigators, may affect the volunteers
ability to participate in the study.
16 Years - 65 Years
Accepts Healthy Volunteers
Jeroen AL Jeneson, PhD, ,
University Medical Center Groningen
Jeroen AL Jeneson, PhD, Principal Investigator, Dept of Neuroscience/ Neuroimaging Center Groningen