Acute Nutritional Ketosis and Exercise in Glycogen Storage Disease Type IIIa
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 6
- 试验地点
- 1
- 主要终点
- 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.
研究概览
简要总结
The investigators will study if acute nutritional ketosis in adult GSD IIIa patients can boost muscle mitochondrial function in vivo.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Other
- 盲法
- Double (Participant, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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
研究组 & 干预措施
Carbohydrate drink
Oral intake - physical exercise
干预措施: physical exercise (Other)
Ketone-ester drink
Oral intake - physical exercise
干预措施: physical exercise (Other)
结局指标
主要结局
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.
时间窗: 10 minutes; during in-magnet exercise test of session II and III.
次要结局
- International Physical Activity Questionnaire(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)
- Blood levels of lactate(Up to 7 samples will be taken during the 25 minutes exercise test (session II and III).)
- 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)
- Blood levels of insulin(Up to 7 samples will be taken during the 25 minutes exercise test (session II and III).)
- Blood levels of NT-proBNP(Up to 7 samples will be taken during the 25 minutes exercise test (session II and III).)
- Change of urine levels of myoglobin, ketones, tetraglucoside(Urine will be collected through study session II and III. A study session will take place from 8 am till 2 pm.)
- 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)
- Change of blood pH(Up to 7 samples will be taken during the 25 minutes exercise test (session II and III).)
- Blood levels of free fatty acids(Up to 7 samples will be taken during the 25 minutes exercise test (session II and III).)
- Blood levels of creatine kinase(Up to 7 samples will be taken during the 25 minutes exercise test (session II and III).)
- optional: individual phenotypic muscle properties (fiber type, mitochondrial density, capillary density(This procedure takes 30 minutes each time and will be performed prior to and immediately post-exercise during study session II and III.)
- 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.)
- Structural muscle parameters: fat infiltration.(During the in-magnet exercise test of 10 minutes during session II and III)
- Change in blood glucose levels(Up to 7 samples will be taken during the 25 minutes exercise test (session II and III).)
- Blood ketones level (β-hydroxybutyrate, acetoacetate).(Up to 7 samples will be taken during the 25 minutes exercise test (session II and III).)
- Blood levels of ammonia(Up to 7 samples will be taken during the 25 minutes exercise test (session II and III).)
- Individual physical performance during exercise; VO2 and VCO2 dynamics.(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.)
- optional: muscle metabolic profile (according to Cox et. al. 2016] of a muscle biopsy.(This procedure takes 30 minutes each time and will be performed prior to and immediately post-exercise during study session II and III.)
研究者
Terry G.J. Derks, MD, PhD
Pediatrician consultant metabolic medicine
University Medical Center Groningen