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Completed

NCT Number: NCT03011203

Acute Nutritional Ketosis in GSD IIIa

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

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Key information

Conditions

Glycogen Storage Disease IIIA Behavior Motor Activity

Age range

18 year–65 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

University of Groningen, UMC Groningen

Groningen, Netherlands

About this study

Glycogen Storage Disease type IIIa (GSD IIIa) is an inborn error of carbohydrate metabolism caused by impaired glycogen debranching enzyme (GDE) activity. The ageing GSD IIIa cohort shows that muscle involvement -despite dietary management- is a common disabling phenotype in adulthood. Currently, no specific therapy has been established for muscle problems in adult GSD IIIa patients.

However, it could be hypothesized that nutritional ketosis (NK) will be highly beneficial to patients. Amongst others, ketone bodies could take on the role of primary energy source in exercising muscle. Recently, acute NK in exercise was studied in humans. NK was found to enhance muscle mitochondrial function in athletes.

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

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • 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.

Exclusion criteria

  • 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

Treatment and study plan

Physical exercise

Other

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

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.

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

Secondary outcomes

  1. time of individual desired workload

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

    #minutes

  2. completion of supine bicycling bout at desired workload in scanner

    Time frame: 10 min

    (yes/no; if no, #minutes)

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

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

    Will be performed during study session I by a neurologist.

  4. Muscle force unilateral

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

    Will be performed during study session I by a neurologist.

  5. Subjective fatigue and muscle ache score

    Time frame: after each exercise bout and 24 hours after exercise

    scale 0-10

  6. International Physical Activity Questionnaire

    Time frame: This questionnaire will take 10 minutes to fill out. Participants will be asked to fill out the questionnaire one week before study session II and III

  7. Structural muscle parameters: fat infiltration.

    Time frame: During the in-magnet exercise test of 10 minutes during session II and III

  8. Change in blood glucose levels

    Time frame: Up to 7 samples will be taken during the 25 minutes exercise test (session II and III).

    #1 and #2 at baseline, #3 after 10 min, #4 after 15 minutes, #5 at the start of bicycle exercise test inside scanner, #6 after 10 minutes of in-magnet exercise and #7 three hours post-exercise inside scanner.

  9. Blood ketones level (β-hydroxybutyrate, acetoacetate).

    Time frame: Up to 7 samples will be taken during the 25 minutes exercise test (session II and III).

    #1 and #2 at baseline, #3 after 10 min, #4 after 15 minutes, #5 at the start of bicycle exercise test inside scanner, #6 after 10 minutes of in-magnet exercise and #7 three hours post-exercise inside scanner.

  10. Change of blood pH

    Time frame: Up to 7 samples will be taken during the 25 minutes exercise test (session II and III).

    #1 and #2 at baseline, #3 after 10 min, #4 after 15 minutes, #5 at the start of bicycle exercise test inside scanner, #6 after 10 minutes of in-magnet exercise and #7 three hours post-exercise inside scanner.

  11. Blood levels of free fatty acids

    Time frame: Up to 7 samples will be taken during the 25 minutes exercise test (session II and III).

    #1 and #2 at baseline, #3 after 10 min, #4 after 15 minutes, #5 at the start of bicycle exercise test inside scanner, #6 after 10 minutes of in-magnet exercise and #7 three hours post-exercise inside scanner.

  12. Blood levels of insulin

    Time frame: Up to 7 samples will be taken during the 25 minutes exercise test (session II and III).

    #1 and #2 at baseline, #3 after 10 min, #4 after 15 minutes, #5 at the start of bicycle exercise test inside scanner, #6 after 10 minutes of in-magnet exercise and #7 three hours post-exercise inside scanner.

  13. Blood levels of creatine kinase

    Time frame: Up to 7 samples will be taken during the 25 minutes exercise test (session II and III).

    #1 and #2 at baseline, #3 after 10 min, #4 after 15 minutes, #5 at the start of bicycle exercise test inside scanner, #6 after 10 minutes of in-magnet exercise and #7 three hours post-exercise inside scanner.

  14. Blood levels of ammonia

    Time frame: Up to 7 samples will be taken during the 25 minutes exercise test (session II and III).

    #1 and #2 at baseline, #3 after 10 min, #4 after 15 minutes, #5 at the start of bicycle exercise test inside scanner, #6 after 10 minutes of in-magnet exercise and #7 three hours post-exercise inside scanner.

  15. Blood levels of NT-proBNP

    Time frame: Up to 7 samples will be taken during the 25 minutes exercise test (session II and III).

    #1 and #2 at baseline, #3 after 10 min, #4 after 15 minutes, #5 at the start of bicycle exercise test inside scanner, #6 after 10 minutes of in-magnet exercise and #7 three hours post-exercise inside scanner.

  16. Blood levels of lactate

    Time frame: Up to 7 samples will be taken during the 25 minutes exercise test (session II and III).

    #1 and #2 at baseline, #3 after 10 min, #4 after 15 minutes, #5 at the start of bicycle exercise test inside scanner, #6 after 10 minutes of in-magnet exercise and #7 three hours post-exercise inside scanner.

  17. Change of urine levels of myoglobin, ketones, tetraglucoside

    Time frame: Urine will be collected through study session II and III. A study session will take place from 8 am till 2 pm.

  18. optional: muscle metabolic profile (according to Cox et. al. 2016] of a muscle biopsy.

    Time frame: This procedure takes 30 minutes each time and will be performed prior to and immediately post-exercise during study session II and III.

    optional, on a patient-voluntary basis. If consent has been given a total of 4 muscle biopsies will be performed.

  19. optional: individual phenotypic muscle properties (fiber type, mitochondrial density, capillary density

    Time frame: This procedure takes 30 minutes each time and will be performed prior to and immediately post-exercise during study session II and III.

    optional, on a patient-voluntary basis. If consent has been given a total of 4 muscle biopsies will be performed.

  20. Individual physical performance during exercise; VO2 and VCO2 dynamics.

    Time frame: During session I; the maximum exercise test of approximately 12 minutes and during the exercise tests of 15 minutes outside the MR scanner at session II and III.

Sponsors and collaborators

Lead sponsor

University Medical Center Groningen

Other

Collaborators

  • Stichting Metakids
  • Stichting Stofwisselkracht
  • University of Oxford
  • University of the Faroe Islands

Registry information

Official study title

Acute Nutritional Ketosis and Exercise in Glycogen Storage Disease Type IIIa

Important dates

Study start
2017
Primary completion
2018
Study completion
2018
First posted
Jan 5, 2017
Registry last updated
May 1, 2018

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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