NCT03011203

Brief Summary

The investigators will study if acute nutritional ketosis in adult GSD IIIa patients can boost muscle mitochondrial function in vivo.

Trial Health

87
On Track

Trial Health Score

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

Enrollment
6

participants targeted

Target at below P25 for not_applicable

Timeline
Completed

Started Feb 2017

Geographic Reach
1 country

1 active site

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

First Submitted

Initial submission to the registry

December 22, 2016

Completed
14 days until next milestone

First Posted

Study publicly available on registry

January 5, 2017

Completed
1 month until next milestone

Study Start

First participant enrolled

February 10, 2017

Completed
1.1 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

March 23, 2018

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

March 23, 2018

Completed
Last Updated

May 1, 2018

Status Verified

April 1, 2018

Enrollment Period

1.1 years

First QC Date

December 22, 2016

Last Update Submit

April 30, 2018

Conditions

Glycogen Storage Disease IIIA

Keywords

glycogen storage disease type IIIaexerciseketone estersmagnetic resonance spectroscopy

Outcome Measures

Primary Outcomes (1)

  • Description of in vivo energy and proton balance during exercise in MR scanner with and without ketone ester drink: steady-state intramuscular levels of glycogen, Pi, PCr and pH and kinetic rate constant of metabolic recovery.

    10 minutes; during in-magnet exercise test of session II and III.

Secondary Outcomes (20)

  • time of individual desired workload

    through completion of the maximum exercise test (of approximately 12 minutes) during study session I.

  • completion of supine bicycling bout at desired workload in scanner

    10 min

  • Muscle ultrasound density of the biceps, quadriceps, calf (gastrocnemius and/or soleus) and tibialis anterior muscles.

    Together with the muscle force examination this assessment will take 1.5 hour.

  • Muscle force unilateral

    Together with the muscle ultrasound this assessment will take 1.5 hour.

  • Subjective fatigue and muscle ache score

    after each exercise bout and 24 hours after exercise

  • +15 more secondary outcomes

Study Arms (2)

Ketone-ester drink

EXPERIMENTAL

Oral intake - physical exercise

Other: physical exercise

Carbohydrate drink

ACTIVE COMPARATOR

Oral intake - physical exercise

Other: physical exercise

Interventions

physical exerciseOTHER

In session II and III participants will perform an exercise test on a bicycle inside and outside the MR scanner.

Carbohydrate drinkKetone-ester drink

Eligibility Criteria

Age18 Years - 65 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • GSD III confirmed with enzyme assay and/or AGL mutation analysis and GSD IIIa further specified as deficient debranching enzyme activity in muscle or clinical and/or biochemical signs of cardiac and/or skeletal muscular involvement.

You may not qualify if:

  • contraindications for MRI studies (assessed by standardised questionnaire)
  • inability to perform bicycle exercise.
  • intercurrent illness which may influence exercise tolerance (anemia, musculoskeletal injury, or other undiagnosed illness under investigation).
  • known coronary artery disease, positive history for angina or cardiomyopathy.
  • insulin-dependent diabetes mellitus.
  • loss of, or an inability to give informed consent.
  • pregnancy or current breastfeeding.
  • any other cause which in the opinion of the investigators, may affect the participant's ability to participate in the study

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

University of Groningen, UMC Groningen

Groningen, Netherlands

Location

Related Publications (6)

  • 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

  • Sentner CP, Hoogeveen IJ, Weinstein DA, Santer R, Murphy E, McKiernan PJ, Steuerwald U, Beauchamp NJ, Taybert J, Laforet P, Petit FM, Hubert A, Labrune P, Smit GPA, Derks TGJ. Glycogen storage disease type III: diagnosis, genotype, management, clinical course and outcome. J Inherit Metab Dis. 2016 Sep;39(5):697-704. doi: 10.1007/s10545-016-9932-2. Epub 2016 Apr 22.

    PMID: 27106217BACKGROUND

  • Verbeek RJ, Sentner CP, Smit GP, Maurits NM, Derks TG, van der Hoeven JH, Sival DA. Muscle Ultrasound in Patients with Glycogen Storage Disease Types I and III. Ultrasound Med Biol. 2016 Jan;42(1):133-42. doi: 10.1016/j.ultrasmedbio.2015.08.013. Epub 2015 Oct 3.

    PMID: 26437929BACKGROUND

  • Preisler N, Laforet P, Madsen KL, Prahm KP, Hedermann G, Vissing CR, Galbo H, Vissing J. Skeletal muscle metabolism is impaired during exercise in glycogen storage disease type III. Neurology. 2015 Apr 28;84(17):1767-71. doi: 10.1212/WNL.0000000000001518. Epub 2015 Apr 1.

    PMID: 25832663BACKGROUND

  • Hoogeveen IJ, de Boer F, Boonstra WF, van der Schaaf CJ, Steuerwald U, Sibeijn-Kuiper AJ, Vegter RJK, van der Hoeven JH, Heiner-Fokkema MR, Clarke KC, Cox PJ, Derks TGJ, Jeneson JAL. Effects of acute nutritional ketosis during exercise in adults with glycogen storage disease type IIIa are phenotype-specific: An investigator-initiated, randomized, crossover study. J Inherit Metab Dis. 2021 Jan;44(1):226-239. doi: 10.1002/jimd.12302. Epub 2020 Sep 7.

    PMID: 33448466DERIVED

MeSH Terms

Conditions

Glycogen Storage Disease IIIAMotor Activity

Interventions

Exercise

Condition Hierarchy (Ancestors)

Behavior

Intervention Hierarchy (Ancestors)

Motor ActivityMovementMusculoskeletal Physiological PhenomenaMusculoskeletal and Neural Physiological Phenomena

Study Officials

  • T.G.J. Derks, MD PhD

    University Medical Center Groningen

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
not applicable
Allocation
RANDOMIZED
Masking
DOUBLE
Who Masked
PARTICIPANT, OUTCOMES ASSESSOR
Purpose
OTHER
Intervention Model
CROSSOVER
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Pediatrician consultant metabolic medicine

Study Record Dates

First Submitted

December 22, 2016

First Posted

January 5, 2017

Study Start

February 10, 2017

Primary Completion

March 23, 2018

Study Completion

March 23, 2018

Last Updated

May 1, 2018

Record last verified: 2018-04

Locations

NL(1)