Glycogen Storage Disease Type II Clinical Trial
Official title:
Fat and Sugar Metabolism During Exercise in Patients With Metabolic Myopathy
This study aims to characterize the pathophysiological mechanisms of 21 different metabolic myopathies. The study will focus on exercise capacity and the metabolic derangement during exercise.
Patients will be compared to a group of matched healthy control subjects (matched for age,
gender, physical activity level and BMI) for comparison of the primary and secondary outcome
measures.
Methods:
Each subject will go through 3 test days.
Test day 1:
- International Physical Activity Questionnaire (IPAQ). The results will be used to match
the patients to control subjects.
- DEXA-scan. This is used to estimate the volume of distribution for stable isotope
tracers.
- Maximal oxidative capacity test (max-test). On a cycle ergometer, subjects will exercise
for approximately 15 minutes with increasing resistance until exhaustion. The peak
oxidative and workload capacities will be compared to the healthy controls and will be
used to find the workload that corresponds to 55-65 % of VO2max used in the following
exercise tests.
- Blood samples. Samples will be drawn before exercise and at exhaustion and will be
analyzed for the plasma concentrations of glucose, lactate, ammonia, creatine kinase and
myoglobin.
Test day 2:
•Long exercise test #1. The purpose of this test is to measure the total fat and sugar
oxidation rates during exercise by using stable isotope tracers.
Subjects arrive at the laboratory after 3-9 hours of fasting. One IV-catheter is inserted in
the cubital vein in one arm and another in a peripheral vein in the other hand. The stable
isotope tracers will be given in the cubital vein as a constant infusion of solutions of:
- [U-13C]-palmitate (0.0026 mg x kg-1 x min-1, after a priming bolus of 0.085 mg x kg-1
NaH13CO3)
- [1,1,2,3,3-2H5]-glycerol (0.0049 mg x kg-1 x min-1 )
- [6.6-2H2]-glucose (0.0728 mg x kg-1 x min-1 ) For two hours the subjects rests while
receiving the infusions until the tracers have distributed in the body and reached a
steady state. After the rest, the subjects exercise on the cycle-ergometer until
exhaustion or for a maximum of 1 hour at an intensity that corresponds to 55-65% of
VO2max.
The heart rate is continuously measured during exercise, and every other minute the subject
evaluates his/her degree of exertion (Rate of Perceived Exertion, RPE) on a Borg scale.
•Blood and breath samples From 20 minutes before exercise and every ten minutes until the end
of exercise, blood samples are drawn and samples of the expired breath are collected.The
breath is analysed for 13CO2 -enrichment. The blood is analysed for the plasma concentrations
of glucose, lactate, ammonia, creatine kinase and myoglobin.
Test day 3:
•Long exercise test #2. The purpose of this test is to investigate exercise capacity and
performance measured as HR, VO2 and RPE during prolonged exercise. To mimic the conditions
for the working muscles in healthy persons who have an intact metabolism, the patients are
given an infusion of a 10% glucose solution to maintain the blood sugar while exercising.
Subjects arrive at the laboratory after 3-9 hours fasting. After 2 hours of rest, the
subjects exercise on the cycle-ergometer until exhaustion or for a maximum of 1 hour at an
intensity that corresponds to 60-65% of VO2max, like they did on test day 2. This time the
subjects are not given stable isotope tracers. 10 minutes before exercising, the subjects are
given a bolus of glucose solution 0.2 g/kg in a cubital vein catheter and a constant infusion
of 10% glucose solution is started (100ml/h). The infusion continues throughout the exercise
period.
Assessments of heart rate, Rate of Perceived Exertion and blood sampling follow the same
protocol as on test day 1, except no breath samples are taken and no analyses of stable
isotopes are made, since the tracers are not used on test day 3.
- Blood samples. From 20 minutes before exercise and every ten minutes until the end of
exercise, blood samples are drawn. The blood is analysed for the plasma concentrations
of glucose, lactate, ammonia, creatine kinase and myoglobin.
- Muscle Biopsy At the end of test day 1 the investigators will perform a voluntary muscle
biopsy.
Statistical Methods:
The investigators will use a paired t-test, two-tailed testing (or the corresponding
non-parametric test, if the assumption of normality is not met). A p-value of < 0.05 will be
considered significant. Results will be reported with Confidence Intervals of the difference
in means. SigmaPlot version 11.0 (or a similar statistical program) will be used for
statistical analysis.
No interim analyses will be made during the 4 days trial period. In the case, that a patient
withdraws/is withdrawn, the obtained data from the completed tests will be included in the
analyses. Raw data that is clearly and indisputably a result of an error in measurement will
not be included (evaluated by the investigator). Missing or lost data will if possible be
reassessed.
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