NCT03531554

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 disorder.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
5

participants targeted

Target at below P25 for not_applicable

Timeline
Completed

Started Apr 2016

Geographic Reach
1 country

2 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

April 1, 2016

Completed
12 months until next milestone

Primary Completion

Last participant's last visit for primary outcome

March 31, 2017

Completed
1 day until next milestone

Study Completion

Last participant's last visit for all outcomes

April 1, 2017

Completed
7 months until next milestone

First Submitted

Initial submission to the registry

October 17, 2017

Completed
7 months until next milestone

First Posted

Study publicly available on registry

May 21, 2018

Completed
Last Updated

May 21, 2018

Status Verified

May 1, 2018

Enrollment Period

12 months

First QC Date

October 17, 2017

Last Update Submit

May 8, 2018

Conditions

VLCAD DeficiencyFatty Acid Oxidation Defects

Keywords

Fatty acid Oxidation Disordersketone esterVLCAD deficiency

Outcome Measures

Primary Outcomes (3)

  • Change of ATP concentration in millimolar

    steady-state in vivo intramuscular concentration of ATP metabolites during rest and exercise.

    During session 2 and 3: continuous measurements from t=75 minutes until t=85 minutes

  • Change of PCr concentration in millimolar

    steady-state in vivo intramuscular concentration of ATP metabolites during rest and exercise.

    During session 2 and 3: continuous measurements from t=75 minutes until t=85 minutes

  • Change of Pi concentration in millimolar

    steady-state in vivo intramuscular concentration of ATP metabolites during rest and exercise.

    During session 2 and 3: continuous measurements from t=75 minutes until t=85 minutes

Secondary Outcomes (35)

  • kinetic rate constant of ATP synthesis in Hertz

    session 2 and 3, 10 minutes each time

  • intramuscular concentration of H+ in millimolar

    session 2 and 3, 10 minutes each time

  • completion of 35 minute upright bicycling bout at FATMAX

    Session 2 and 3, 35 minutes

  • completion of 10 minute supine bicycling bout at FATMAX in scanner

    Session 2 and 3, 10 minutes

  • HR in beats per minute

    During session 1, 15 minutes During Session 2 + 3: 35 minutes

  • +30 more secondary outcomes

Study Arms (2)

ketone ester drink

EXPERIMENTAL

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

Dietary Supplement: ketone ester drinkBehavioral: exerciseProcedure: muscle biopsyDiagnostic Test: Magnetic Resonance Imaging

carbohydrate drink

PLACEBO COMPARATOR

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

Behavioral: exerciseProcedure: muscle biopsyDiagnostic Test: Magnetic Resonance Imaging

Interventions

ketone ester drinkDIETARY_SUPPLEMENT

395 mg of ketone ester/kg

Also known as: deltaG (R)
ketone ester drink
exerciseBEHAVIORAL

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

carbohydrate drinkketone ester drink
muscle biopsyPROCEDURE

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

carbohydrate drinkketone ester drink
Magnetic Resonance ImagingDIAGNOSTIC_TEST

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

Also known as: Magnetic Resonance Spectroscopy
carbohydrate drinkketone ester drink

Eligibility Criteria

Age16 Years - 65 Years
Sexall
Healthy VolunteersNo
Age GroupsChild (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

  • \- Confirmed VLCADD by genetic profiling

You may not qualify if:

  • 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.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (2)

Academic Medical Center

Amsterdam, North Holland, 1105 AZ, Netherlands

Location

Dept of Neuroscience/ Neuroimaging Center

Groningen, 9700RB, Netherlands

Location

Related Publications (3)

  • Cox PJ, Kirk T, Ashmore T, Willerton K, Evans R, Smith A, Murray AJ, Stubbs B, West J, McLure SW, King MT, Dodd MS, Holloway C, Neubauer S, Drawer S, Veech RL, Griffin JL, Clarke K. Nutritional Ketosis Alters Fuel Preference and Thereby Endurance Performance in Athletes. Cell Metab. 2016 Aug 9;24(2):256-68. doi: 10.1016/j.cmet.2016.07.010. Epub 2016 Jul 27.

    PMID: 27475046BACKGROUND

  • Diekman EF, Visser G, Schmitz JP, Nievelstein RA, de Sain-van der Velden M, Wardrop M, Van der Pol WL, Houten SM, van Riel NA, Takken T, Jeneson JA. Altered Energetics of Exercise Explain Risk of Rhabdomyolysis in Very Long-Chain Acyl-CoA Dehydrogenase Deficiency. PLoS One. 2016 Feb 16;11(2):e0147818. doi: 10.1371/journal.pone.0147818. eCollection 2016.

    PMID: 26881790BACKGROUND

  • Bleeker JC, Visser G, Clarke K, Ferdinandusse S, de Haan FH, Houtkooper RH, IJlst L, Kok IL, Langeveld M, van der Pol WL, de Sain-van der Velden MGM, Sibeijn-Kuiper A, Takken T, Wanders RJA, van Weeghel M, Wijburg FA, van der Woude LH, Wust RCI, Cox PJ, Jeneson JAL. Nutritional ketosis improves exercise metabolism in patients with very long-chain acyl-CoA dehydrogenase deficiency. J Inherit Metab Dis. 2020 Jul;43(4):787-799. doi: 10.1002/jimd.12217. Epub 2020 Feb 5.

    PMID: 31955429DERIVED

MeSH Terms

Conditions

VLCAD deficiency

Interventions

ExerciseMagnetic Resonance ImagingPositron-Emission Tomography

Intervention Hierarchy (Ancestors)

Motor ActivityMovementMusculoskeletal Physiological PhenomenaMusculoskeletal and Neural Physiological PhenomenaTomographyDiagnostic ImagingDiagnostic Techniques and ProceduresDiagnosisTomography, Emission-ComputedImage Interpretation, Computer-AssistedImage EnhancementPhotographyRadionuclide ImagingDiagnostic Techniques, Radioisotope

Study Officials

  • Jeroen AL Jeneson, PhD

    Dept of Neuroscience/ Neuroimaging Center Groningen

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
not applicable
Allocation
RANDOMIZED
Masking
DOUBLE
Who Masked
PARTICIPANT, OUTCOMES ASSESSOR
Masking Details
Double (Participant, Outcomes Assessor)
Purpose
OTHER
Intervention Model
CROSSOVER
Model Details: randomized, blinded, placebo controlled, 2-way cross-over trial
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Principal Investigator

Study Record Dates

First Submitted

October 17, 2017

First Posted

May 21, 2018

Study Start

April 1, 2016

Primary Completion

March 31, 2017

Study Completion

April 1, 2017

Last Updated

May 21, 2018

Record last verified: 2018-05

Locations

NL(2)