Clinical Trial: Acute Nutritional Ketosis in GSD IIIa
Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional
Official Title: Acute Nutritional Ketosis and Exercise in Glycogen Storage Disease Type IIIa
Brief Summary: The investigators will study if acute nutritional ketosis in adult GSD IIIa patients can boost muscle mitochondrial function in vivo.
Detailed Summary:
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.
Sponsor: University Medical Center Groningen
Current Primary Outcome: 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. ]
Original Primary Outcome:
- Description of 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. ]
- 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. ]
Current Secondary Outcome:
- time of individual desired workload [ Time Frame: through completion of the maximum exercise test (of approximately 12 minutes) during study session I. ]#minutes
- completion of supine bicycling bout at desired workload in scanner [ Time Frame: 10 min ](yes/no; if no, #minutes)
- 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.
- 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.
- Subjective fatigue and muscle ache score [ Time Frame: after each exercise bout and 24 hours after exercise ]scale 0-10
- 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 ]
- Structural muscle parameters: fat infiltration. [ Time Frame: During the in-magnet exercise test of 10 minutes during session II and III ]
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- Change of urine levels of myoglobin, ketones, tetraglucoside [ Time&nbs
Original Secondary Outcome:
- time of individual desired workload [ Time Frame: through completion of the maximum exercise test (of approximately 12 minutes) during study session I. ]#minutes
- completion of supine bicycling bout at desired workload in scanner [ Time Frame: 10 min ](yes/no; if no, #minutes)
- 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.
- 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.
- Subjective fatigue and muscle ache score [ Time Frame: after each exercise bout and 24 hours after exercise ]scale 0-10
- 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 ]
- Structural muscle parameters: fat infiltration. [ Time Frame: During the in-magnet exercise test of 10 minutes during session II and III ]
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- Change of urine levels of myoglobin, ketones, tetraglucoside [ Time&nbs
Information By: University Medical Center Groningen
Dates:
Date Received: December 22, 2016
Date Started: February 10, 2017
Date Completion: February 2019
Last Updated: February 15, 2017
Last Verified: February 2017
- time of individual desired workload [ Time Frame: through completion of the maximum exercise test (of approximately 12 minutes) during study session I. ]
