McArdle Disease Clinical Trial
Official title:
Oral Ketone Body Supplementation in Patients With McArdle Disease
McArdle disease, glycogen storage disease type V, is a rare metabolic disease. Affected
individuals are unable to utilize sugar stored as glycogen in muscle.
Investigators hypothesize that ketones can be an alternative fuel substrate for skeletal
muscle when muscle glycogenolysis is blocked as in McArdle disease.
In this study investigators will investigate the immediate effects of an oral supplementation
of exogenous ketone bodies (poly-hydroxybuturate) on exercise capacity in patients with
metabolic myopathies, compared with a placebo drink.
McArdle disease, glycogen storage disease type V, is a rare metabolic disease caused by
mutations in the PYGM gene resulting in absence of the enzyme muscle phosphorylase. Affected
individuals are unable to utilize sugar stored as glycogen in muscle, leading to exercise
intolerance, exercise-induced muscle pain, contractures and rhabdomyolysis, which may cause
renal failure. Currently, there are no satisfactory treatment options for McArdle disease.
A key element of alleviating symptoms in McArdle disease is to provide alternative fuels for
energy metabolism. Investigators hypothesize that ketones can be an alternative fuel
substrate for skeletal muscle when muscle glycogenolysis is blocked as in McArdle disease.
Aim: To investigate the immediate effects of an oral supplementation of exogenous ketone
bodies (poly-hydroxybuturate) on exercise capacity in patients with metabolic myopathies.
Supplement description: food supplement containing β-hydroxybuturate esters
Methods:
Study design: Placebo-controlled, single-blind, cross-over study. Inclusion: 5-8 patients
with McArdle disease and 3-5 healthy controls.
Time table:
Subjects will meet to 2 test days. Subjects will be randomized using a 1:1 assignment ratio
to receive either the keto-drink or placebo drink first. The oral supplement received will be
blinded for the participants and the investigators. On each test day, subjects spend
approximately 4 hours at the laboratory:
- Insertion of peripheral brachial venous catheters for extracting blood samples and
stable isotope infusion and hydroxybutyrate infusion.
- Baseline blood sampling, medical examination, vital sign measurements, weight and
height.
- Stable isotope infusion 2 hours before the cycling exercise test. Three stable isotope
tracers [2,4-13C2]-D- β-hydroxybutyrate, [1,1,2,3,3-2H5]-glycerol and [6,6-2H2]-glucose
solutions, are infused via a venous catheter until a steady-state is reached. The tracer
infusions will continue during the cycling test. The tracers (all from Cambridge Isotope
Laboratories, Andover, MA, USA) will be dissolved and injected into a solution of 0.9%
saline (NaCl) through a bacterial filter.
- One Ketone or placebo drink administration 30 minutes before the exercise test
- Subjects will perform a 40 minutes cycle exercise test at a constant load corresponding
to 60-70% of their VO2max (found in a screening study). During the test, subjects wear a
mask for continuous gas-exchange measurements and ECG electrodes to determine VO2 and
heart rate during constant load cycling (VO2const and HRconst). Blood samples will be
drawn 4 times before, every 10 minutes during exercise and after exercise. During the
test participants will be asked to rate perceived exertion (RPE) on a Borg scale.
;
Status | Clinical Trial | Phase | |
---|---|---|---|
Completed |
NCT04349566 -
Fast Troponin as a Biomarker to Assess Exercise-induced Muscle Damage in Muscle Diseases
|
||
Enrolling by invitation |
NCT03211923 -
Muscle Relaxation in Myopathies With Positive Muscle Phenomena
|
||
Completed |
NCT03112889 -
Sodium Valproate for GSDV
|
Phase 2 | |
Completed |
NCT04694547 -
Ketogenic Diet Survey in Patients With McArdle Disease (GSDV)
|
||
Completed |
NCT03843606 -
Modified Ketogenic Diet in Patients With McArdle Disease Part A
|
N/A | |
Recruiting |
NCT04929002 -
Carbon-13 Magnetic Resonance Spectroscopy in Glycogen Storage Diseases
|
||
Completed |
NCT04226274 -
A Study of the Safety of REN001 in Patients With McArdle Disease
|
Phase 1 | |
Completed |
NCT04044508 -
Modified Ketogenic Diet in Patients With McArdle Disease Part B
|
N/A | |
Recruiting |
NCT05943678 -
Novel Metabolic Muscular Biomarkers in Pompe Disease - a Non-invasive Magnetic Resonance Exploratory Pilot Study.
|