The primary objective is to determine the effect of dietary ribose supplementation on muscle function in patients with isolated LGMD as caused by a dystroglycanopathy. The secondary aim is to determine if ribose is well tolerated in this patient…
Source
Brief title
Condition
- Muscle disorders
Synonym
Research involving
Sponsors and support
Intervention
No registrations found.
Outcome measures
Primary outcome
Primary study parameters include effectiveness of sugar supplementation on
improved muscle function as investigated by standardized questionnaires and
muscle function tests and a muscle biopsy.
Secondary outcome
Secondary study parameter includes if sugar supplementation is well tolerated
in this patient group.
Background summary
Dystroglycanopathies are orphan diseases, forming a subgroup of the Congenital
Muscular Dystrophies with central nervous system involvement. Less severe forms
of the disease result in isolated limb-girdle muscular dystrophy (LGMD) at
later age. Currently, no causative treatment exists for any form of the
dystroglycanopathies.
The pathogenic mechanism is based on deficient modification of the protein
alpha-Dystroglycan (aDG) with glycans. These glycans are composed of
monosaccharides that are derived from the food or are synthesized in the body.
Deficient aDG glycosylation results in deficient binding of the muscle membrane
to the extracellular matrix, thereby resulting in muscular dystrophy. Over 15
different genetic defects have been identified as cause of this group of
diseases.
Recently, we discovered the function of one of these genetic defects, ISPD. The
ISPD enzyme produces the sugar CDP-ribitol. We found that supplementation of
culture patient cells with ribitol and ribose improved the levels of the
CDP-ribitol sugar and also restored the glycosylation of aDG. Since ribose has
been used as a safe and naturally occurring food supplement in human, these
data indicate a potential safe way to intervene in dystroglycanopathy patients
due to ISPD mutations.
Study objective
The primary objective is to determine the effect of dietary ribose
supplementation on muscle function in patients with isolated LGMD as caused by
a dystroglycanopathy. The secondary aim is to determine if ribose is well
tolerated in this patient group.
Study design
Patients will be assessed for muscle function and strength, via standardized
questionnaires and by clinical chemistry parameters in blood and urine before
start of dietary supplementation. After start of therapy, these investigations
will be repeated every two months during 8 months. After 6 months, additionally
a muscle biopsy will be taken to assess improved muscle function biochemically.
Intervention
Intervention involves daily dietary intake of the monosaccharide ribose.
Study burden and risks
Participants will be asked for a visit to the outpatient clinic at the
department of Neurology of the Radboudumc or collaborating institutions abroad.
Their medical history will be taken, they will undergo a clinical examination
and they will fill out questionnaires. Blood and urine samples will be
collected before and during ribose supplementation. Participants will undergo a
muscle biopsy of the leg after 6 months of treatment, unless they object
against this procedure. This material will be used for biochemical assessment
of the response to ribose. Complications of (muscle) biopsies are very uncommon
and include hematoma and very localized loss of sensation of the skin
(hypesthesia). The dietary monosaccharides are used as safe food supplement. In
case of fasting, ribose at much higher concentrations than used in this study
were reported to result in lowered blood glucose levels. To avoid such
potential risks, patients will take ribose in the fed-state. We classify the
risk of this study as negligible.
Geert grooteplein 10
Nijmegen 6525 GA
NL
Geert grooteplein 10
Nijmegen 6525 GA
NL
Listed location countries
Age
Inclusion criteria
- Confirmed Congenital muscular dystrophy with mutations in ISPD, FKRP, or FKTN
- Dystroglycan dysfunction in muscle
- Normoglycemic before start of supplementation
- Isolated muscle dystrophy, no central nervous system symptoms
- Age >18 years
Exclusion criteria
Persons with contra-indications for a muscle biopsy or who are unwilling to undergo a biopsy, are excluded for that one procedure, but can still be included in the study. Patients with a known condition of severe hypoglycaemia in the fed-state will not be included in this study.
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
Register | ID |
---|---|
CCMO | NL58620.091.16 |