Acute Nutritional Ketosis in VLCAD Deficiency

Brief Title

Acute Nutritional Ketosis in VLCAD Deficiency

Official Title

Acute Nutritional Ketosis in VLCAD Deficiency: Testing the Metabolic Base for Therapeutic Use

Brief Summary

      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

Detailed Description

      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.

Study Type


Primary Outcome

Change of ATP concentration in millimolar

Secondary Outcome

 kinetic rate constant of ATP synthesis in Hertz


VLCAD Deficiency


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.

Recruitment Information

Recruitment Status

Dietary Supplement

Estimated Enrollment


Start Date

April 1, 2016

Completion Date

April 1, 2017

Primary Completion Date

March 31, 2017

Eligibility Criteria

        Inclusion Criteria:

        - Confirmed VLCADD by genetic profiling

        Exclusion Criteria:

          -  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, , 

Location Countries


Location Countries


Administrative Informations



Organization ID


Responsible Party

Principal Investigator

Study Sponsor

University Medical Center Groningen


 UMC Utrecht

Study Sponsor

Jeroen AL Jeneson, PhD, Principal Investigator, Dept of Neuroscience/ Neuroimaging Center Groningen

Verification Date

May 2018