The main objective of this prospective population based cohort study of patients with KD in the Netherlands and Flemish part of Belgium is to perform multiple tests (i.e. clinical and blood) and genomic profiling to discover possible biomarkers for…
ID
Source
Brief title
Condition
- Chromosomal abnormalities, gene alterations and gene variants
- Endocrine disorders of gonadal function
- Neuromuscular disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The main study parameters of this study are the correlations between possible
biomarkers and the disease progression in patients. Disease status and
progression will be measured with the ALS-FRS-R, Norris scale and ShortForm-36.
Possible biomarkers are the manual muscle testing, 6minute-walking-test,
circumference of limbs, bloodtesten (transaminases, creatine kinase, glucose,
HbA1c, prolactine, testosterone, luteinizing hormone, follicle stimulating
hormone and sex-hormone-binding-globuline) and genomic profiling of mRNA. With
the discovery of (a) new biomarker(s) the sample size calculation for drug
efficacy trials in KD can be made.
Secondary outcome
NA
Background summary
Kennedy Disease (KD), also called spinal and bulbar muscular atrophy, is a
neurodegenerative disorder of motor neurons characterized by proximal muscle
weakness and atrophy, bulbar involvement, hand tremor, mild sensory symptoms
and gynaecomastia. Although the majority of symptoms comprises motor function,
sensory disturbances can also occur. Kennedy Disease is a so-called X-linked
polyglutamine disease with an expansion of the CAGrepeat at the N-terminal of
the Androgen Receptor (AR) gene. Testosterone plays a major part in the
pathogenesis of KD, because binding of testosterone at mutant AR induces a
toxic gain of function of the AR with subsequent neuronal degeneration. Despite
the knowledge of the pathogenesis and underlying genetic defect, a treatment to
cure or stabilize KD has not yet been discovered. Limitations of efficacy
trials in KD are the rarity of the disease, the slow progression of the disease
and the required extensive trial duration.
Study objective
The main objective of this prospective population based cohort study of
patients with KD in the Netherlands and Flemish part of Belgium is to perform
multiple tests (i.e. clinical and blood) and genomic profiling to discover
possible biomarkers for disease progression in KD. New biomarkers in KD are
needed to effectively screen future disease-modifying therapies.
Study design
A prospective, population based cohort study
Study burden and risks
This research will be done in patients with KD. The burden of participation
consists of filling out a questionnaire, undergoing physical examination and
the drawing of blood samples every six months. The blood amount varies per
visit from 2 tubes (3ml + 3.5ml) up to 5 tubes (10ml + 10ml + 3ml + 3.5ml +
2.5ml). Every six months multiple functional tests will be performed. Overall,
the burden and risks associated with participation in the study will be minor.
Heidelberglaan 100
3584 CX Utrecht
NL
Heidelberglaan 100
3584 CX Utrecht
NL
Listed location countries
Age
Inclusion criteria
1) genetically confirmed KD in patients with more than one of the following symptoms,: muscle weakness, muscle atrophy, bulbar palsy, fasciculations, tremor or mild sensory symptoms
2) male
3) Androgen receptor gene with a CAG repeat exceeding 38 copies
4) age >18 years
5) given written informed consent
Exclusion criteria
1) Androgen receptor gene with CAG repeat of less than 38 repeats
2) female carriers
3) <18 years of age
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 | NL29819.041.09 |