NCT03531554

Acute Nutritional Ketosis in VLCAD Deficiency

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

• Status: Completed
• Phase: N/A
• Study type: Interventional
• Enrollment: 5 (actual)
• Sponsor: University Medical Center Groningen · Academic / Other
• Sex: All
• Age: 16 Years – 65 Years
• Healthy volunteers: Not accepted

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 disorder.

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.

Conditions

• VLCAD Deficiency
• Fatty Acid Oxidation Defects

Interventions

Type	Name	Description
DIETARY_SUPPLEMENT	ketone ester drink	395 mg of ketone ester/kg
BEHAVIORAL	exercise	35 min cycling test on an upright bicycle, followed by 10 minutes of supine cycling inside a MR scanner.
PROCEDURE	muscle biopsy	biopsy from the quadriceps muscle prior to and immediately after upright bicycling
DIAGNOSTIC_TEST	Magnetic Resonance Imaging	1H MR images and 31P MR spectra were acquired from the upper leg prior to-, during and after exercise

Timeline

• Start date: 2016-04-01
• Primary completion: 2017-03-31
• Completion: 2017-04-01
• First posted: 2018-05-21
• Last updated: 2018-05-21

Locations

2 sites across 1 country: Netherlands