We aim at investigating the interplay between DUX4 and inflammation in FSHD combining MRI imaging, histology, gene and cytokine expression.
ID
Source
Brief title
Condition
- Muscle disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Main outcomes will be: evaluation of inflammation in muscles using MRI;
differential immunohistological characterization of muscle biopsies between
patients and controls; difference in genomic expression profiling and cytokine
profiling on blood cells and muscle tissue between patients and controls.
Secondary outcome
Secondary objectives are:
1) Assess FSHD Severity Score
2) Evaluates muscle weakness degree by MRC grading.
3) Compare the diagnostic quality of MRI and 3D ultrasound images in order to
develop future 3D US guided biopsies.
4) Compare the 3D ultrasound images of patients with already acquired 3D US of
healthy volunteers in order to understand possible factor contributing to
muscle weakness in FSHD.
Background summary
Facioscapulohumeral dystrophy (FSHD) is one of the most prevalent inherited
myopathies and is caused by the transcriptional de-repression of DUX4, a
transcription factor, in skeletal muscle, responsible for a deregulation
cascade resulting in the miss-expression of several immune genes, retroelements
and germlines genes in FSHD muscle. Moreover, recent studies describe muscle
inflammatory infiltrates mainly composed by CD8+ T cells in muscles showing
hyperintensity features on T2-weighted short tau inversion recovery magnetic
resonance imaging (T2-STIR-MRI) sequences. We wonder if and which relationship
exists between DUX4 activation and muscle inflammation in FSHD and we
hypothesize that DUX4 induced muscle inflammation can ultimately lead to
dystrophy.
Study objective
We aim at investigating the interplay between DUX4 and inflammation in FSHD
combining MRI imaging, histology, gene and cytokine expression.
Study design
The study has an explorative and observational nature and it will be perform as
a case-control study involving FSHD patient and healthy controls.
Study burden and risks
A total of 40 subjects will undergo a muscle biopsy. A maximum of 100 patients
will be asked to join the screening procedure: 1) complete medical history; 2)
blood samples collection; 3) MRI screeing scan of shoulders, upper arm and leg;
4) 3D US of one clinically affected muscel of the leg.The screening will close
with the first 25 FSHD patietns reporting a MRI-STIR positivity. There are
minimal risks associated with blood sampling: bleeding, a slight risk of
infection, fainting or feeling light-headed. There are no associated risk with
the 3D US examination and only one affected muscle of the leg will be screened
only in the patient group. Also, 25 patients will undergo an MRI guided muscle
biopsy of the leg, similar to a previous approved study conducted by Drs S.
Lassche (Why are FSHD muscles weak? NL35549.091.11). 15 healthy controls will
be asked for a needle biopsy from the leg at the outpatient clinic of the
neurology department. Complications of muscle biopsies are very uncommon and
include hematoma and hypoesthesia. Therefore we classify the risk of this study
as negligible.
Reinier Postlaan 4
Nijmegen 6525 GC
NL
Reinier Postlaan 4
Nijmegen 6525 GC
NL
Listed location countries
Age
Inclusion criteria
- > 18 year old
- Genetically confirmed FSHD
- unrelated
- with symptomatic lower limb weakness
Exclusion criteria
- Age <18
- Diabetes mellitus
- Chronic obstructive pulmonary disease
- Current malignancy
- Current use of corticosteroids
- Current use of statines
- Contra-indications for MRI-scan or muscle biopsy
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 | NL64690.091.18 |