Acute Nutritional Ketosis in VLCAD Deficiency

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

NA

Total Enrollment

5 participants

Study Classification

INTERVENTIONAL

Study Start Date

2016-04-01

Study Completion Date

2017-04-01

Brief Summary

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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.

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Detailed Description

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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

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VLCAD Deficiency Fatty Acid Oxidation Defects

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

CROSSOVER

randomized, blinded, placebo controlled, 2-way cross-over trial

Primary Study Purpose

OTHER

Blinding Strategy

DOUBLE

Participants Outcome Assessors

Double (Participant, Outcomes Assessor)

Study Groups

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ketone ester drink

Oral intake of ketone ester drink muscle biopsy exercise muscle biopsy Magnetic Resonance imaging

Group Type EXPERIMENTAL

ketone ester drink

Intervention Type DIETARY_SUPPLEMENT

395 mg of ketone ester/kg

exercise

Intervention Type BEHAVIORAL

35 min cycling test on an upright bicycle, followed by 10 minutes of supine cycling inside a MR scanner.

muscle biopsy

Intervention Type PROCEDURE

biopsy from the quadriceps muscle prior to and immediately after upright bicycling

Magnetic Resonance Imaging

Intervention Type DIAGNOSTIC_TEST

1H MR images and 31P MR spectra were acquired from the upper leg prior to-, during and after exercise

carbohydrate drink

Oral intake of isocaloric carbohydrate drinkmuscle biopsy exercise muscle biopsy Magnetic Resonance imaging

Group Type PLACEBO_COMPARATOR

exercise

Intervention Type BEHAVIORAL

35 min cycling test on an upright bicycle, followed by 10 minutes of supine cycling inside a MR scanner.

muscle biopsy

Intervention Type PROCEDURE

biopsy from the quadriceps muscle prior to and immediately after upright bicycling

Magnetic Resonance Imaging

Intervention Type DIAGNOSTIC_TEST

1H MR images and 31P MR spectra were acquired from the upper leg prior to-, during and after exercise

Interventions

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ketone ester drink

395 mg of ketone ester/kg

Intervention Type DIETARY_SUPPLEMENT

exercise

35 min cycling test on an upright bicycle, followed by 10 minutes of supine cycling inside a MR scanner.

Intervention Type BEHAVIORAL

muscle biopsy

biopsy from the quadriceps muscle prior to and immediately after upright bicycling

Intervention Type PROCEDURE

Magnetic Resonance Imaging

1H MR images and 31P MR spectra were acquired from the upper leg prior to-, during and after exercise

Intervention Type DIAGNOSTIC_TEST

Other Intervention Names

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deltaG (R) Magnetic Resonance Spectroscopy

Eligibility Criteria

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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 months.
* 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.

Minimum Eligible Age

16 Years

Maximum Eligible Age

65 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No