The primary objective of this CMO application is to acquire follow-up MRI data of the skeletal muscles in FSHD patients to investigate the progression in fat infiltration and changes in muscle volume in these patients after 3-4 years, by using the…
ID
Source
Brief title
Condition
- Muscle disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The change in fat fraction and muscle volume over 3-4 years in the lower
extremity muscles of FSHD patients
Secondary outcome
1) The effect of fat infiltration and STIR/TIRM hyper intensity at the baseline
scan on the change in fat fraction and muscle volume over 3-4 years. To
evaluate this we will first determine the percentage of muscles that were
* Intermediately fat infiltrated at baseline that became fully fat infiltrated
in 3-4 years
* Non-fat infiltrated at baseline that became intermediately fat infiltrated in
3-4 years
* Non-fat infiltrated at baseline that remained non-fat infiltrated after 3-4
years
* STIR/TIRM hyper intensity at baseline and showed increased fat fraction in
3-4 years
Second, we will apply a linear mixed model, see statistics paragraph.
2) Outcome measures for evaluating the pattern of infiltration in the baseline
MRI scan are:
* Fit quality (r2) of each model for every muscle.
* The percentage of muscles where a) model A is the best fit b) model B is the
best, c) model C is the best fit
Background summary
Facioscapulohumeral muscular dystrophy (FSHD) is a hereditary disease
characterized by progressive loss of muscle strength. Since the DUX4 gene has
been discovered as the genetic cause for FSHD the development of new treatments
focuses on this genetic abnormality. However, to develop and evaluate
successful treatments it is equally important to understand what mechanism
initiates the production of toxic DUX4 proteins and to understand the normal
disease progression.
The loss of muscle strength in FSHD is strongly related to the replacement of
muscle tissue by fat, and by muscle cell loss and reduction of muscle cell
size. Identifying where this fat replacement starts may give clues on what
mechanisms are responsible for disease initiation. Magnetic Resonance Imaging
(MRI) is an ideal tool to investigate this, because it allows quantitative
assessment of the intramuscular fat percentage and muscle volume of whole
muscles from tendon to tendon.
Furthermore, MRI findings on natural progression over 4 months indicates that
once a muscle starts to become fat infiltration, complete fatty replacement of
an affected muscle on average occurs in about 3.5 years. This knowledge is of
great clinical use, but requires confirmation in longitudinal studies over
longer time periods.
Study objective
The primary objective of this CMO application is to acquire follow-up MRI data
of the skeletal muscles in FSHD patients to investigate the progression in fat
infiltration and changes in muscle volume in these patients after 3-4 years, by
using the already acquired baseline MRI data of the aTYR1940 study
(NL49110.091.14). The first secondary objective, is to investigate if these
changes in fat infiltration and muscle volume differ between non-fat
infiltrated muscles vs. fat infiltrated muscles at baseline and STIR/TIRM
hyperintense muscles vs. STIR/TIRM normo-intense muscles at baseline. The
second secondary objective is to determine the pattern of intramuscular fat
infiltration in muscles of patients with FSHD.
Study design
Observational MRI study to acquire follow-up MRI scans of the skeletal muscles
in FSHD patients who underwent 3-4 years ago a MRI scan of the whole lower
extremity for the aTYR1940 study (NL49110.091.14).
Study burden and risks
The proposed study is fully non-invasive. Therefore, burden and risk is
minimal. The patients will undergo one MRI scan with a maximum duration of 90
minutes. Patients participating in this study will not derive any direct
benefit, but considering the general benefits for the FSHD population it can be
concluded that the benefits outweigh the burden and negligible risk (NFU
document *Kwaliteitsborging mensgebonden onderzoek 2.0*) associated with this
study.
Geert Grooteplein-Zuid 10
Nijmegen 6500 HB
NL
Geert Grooteplein-Zuid 10
Nijmegen 6500 HB
NL
Listed location countries
Age
Inclusion criteria
Genetically confirmed FSHD
Adult (> 18 years old)
Already underwent a MRI scan of the whole lower extremity ± 3 years ago
Exclusion criteria
contra-indications for undergoing a MRI scan (e.g. because of pacemaker, claustrophobia, metal implants, metal splinters in the eye)
inability to lie supine for 90 minutes.
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 | NL66071.091.18 |