Hoofddoel: We aim to assess the utility of ultrasound-defined contractile performance as a biomarker for monitoring disease progression and treatment effects in patients with FSHD.Stage I:Primary Objective:To establish the feasibility, optimal…
ID
Source
Brief title
Condition
- Musculoskeletal and connective tissue disorders congenital
- Muscle disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Stage I:
In the first stage, we will focus on the data collected using the Biodex
system. The primary outcome parameter is repeatability, where we examine the
degree of agreement of the repeated ultrasound measurements with the force
generation and surface electromyography (sEMG) measurements:
o Biodex: Dynamometric force generation
Peak torque (Nm)
Time to peak torque (mSec)
Angle of peak torque (Deg)
Time rate of stress development (Nm)
o Ultrasound: speckle detection
Deformation (%)
Displacement (mm)
Muscle contractile performance
o Ultrasound: Ultrafast Shear Wave Elastography Imaging (UF-SWEI)
Muscle stiffness (N/mm2)
o sEMG
Neural input/activation (mV)
Stage I data will first be collected from 15 healthy participants by performing
3 repeated measures to develop the most feasible and repeatable protocol for
this group. Subsequently, the same repetitive measurements are performed in 10
patients with FSHD type 1 or 2 to check whether the protocol is also feasible
and repeatable in patients or whether adjustments are required.
Phase II:
In addition to the measurements in stage I, stage II will focus on collecting
Biodex measures from more patients (n=50) and healthy participants (n=25).
Furthermore, all patients will receive an MRI scan. Based on the MRI data, we
mainly look at the amount of fat and edema present in the muscle, but also at
the muscle contraction volume. In stage 2, the primary outcome parameter is the
relationship between muscle contraction performance, clinical measures, other
ultrasound and MRI measures in both healthy participants and patients with
FSHD. The second outcome parameter is the responsiveness to change after 1 year
of follow-up of the parameters mentioned in the stages above.
Secondary outcome
N.A.
Background summary
FSHD is a slowly progressive muscle dystrophy characterized by initial
asymmetrical weakness. However, the straightforward assumption that loss of
muscle fibers can be linearly translated to loss of strength has recently been
challenged. There is still a lack of studies about how the disrupted muscle
architecture in muscle dystrophies influences the contractile performance.
Therefore, it is possible that muscle contractile performance may be the
intermediate factor in FSHD strength loss. Muscle imaging has previously
contributed to a better understanding of the pathophysiology of various
neuromuscular disorders. Both MRI and ultrasound have proven their clinical
relevance in neuromuscular dystrophy. With the current development of FSHD
clinical trials, the extensive need for biomarkers to follow disease
progression is growing. To investigate whether muscle contractile performance
can help explain the loss in strength and thereby also has the potential to act
as a future biomarker, will be explored in this project.
Study objective
Hoofddoel: We aim to assess the utility of ultrasound-defined contractile
performance as a biomarker for monitoring disease progression and treatment
effects in patients with FSHD.
Stage I:
Primary Objective:
To establish the feasibility, optimal protocol, and repeatability of
quantifying ultrasound-defined muscle contractile performance in the upper and
lower limb muscles in healthy volunteers and patients with FSHD.
Stage II:
Primary Objectives:
1. To determine the differences in ultrasound-defined contractile performance
between healthy individuals and patients with FSHD, and compare to conventional
clinical measures, ultrasound measures and MRI measures.
2. To determine the responsiveness of ultrasound-defined contractile
performance to disease progression in FSHD patients after 1 year, and compare
to MRI measures and other ultrasound measures.
Study design
This prospective cohort study consists of two distinct stages. In stage I, the
feasibility and repeatability of the qualitative ultrasound-defined muscle
contractile performance will be assessed. In phase II, the differences in
ultrasound-defined contractile performance between healthy subjects and
patients with FSHD are examined and also compared with other ultrasound
parameters, clinical parameters and MRI parameters. In addition, the
responsiveness to change after 1 year is also analyzed.
Study burden and risks
In this study, the risks to the participants are negligible. Participants do
not directly benefit from a contribution to this project. The scientific
benefit of this project is the future availability of a potential new imaging
biomarker that responds to changes and can be used in new clinical trials.
Subjects in stage 1:
Healthy participants are expected to visit Radboudumc once in stage 1. Patients
with FSHD are also expected to visit Radboudumc once in stage 1
Subjects in stage 2:
Healthy participants are expected to visit the hospital at least 1 time and
maximal 2 times in stage 2 Patients are expected to visit the Radboudumc at
least 4 times in due to the follow-up measurements after 1 year (there is a
possibility some measurements can be scheduled at the same day ).
Geert Grooteplein Zuid 10
Nijmegen 6525GA
NL
Geert Grooteplein Zuid 10
Nijmegen 6525GA
NL
Listed location countries
Age
Inclusion criteria
All participants:
• Age between 18 and 70 years.
• Informed consent is given by the participant.
• Ability to read and understand written and spoken instruction in Dutch.
• Willingness and ability to understand nature and content of the study.
Patients with FSHD:
• Clinically and genetically proven FSHD type 1 or type 2.
Exclusion criteria
A potential subject who meets any of the following criteria will be excluded
from participation in this study:
All participants:
• BMI >= 35
• Other diseases that could diffusely affect muscle integrity or disturb the
imaging appearance beyond that what can be extrapolated.
• Wheelchair dependence.
• Pregnancy
In stage 2: participants who will undergo an MRI-scan
-Any contra-indications for MRI, including:
o Claustrophobia
o Pacemakers and defibrillators
o Nerve stimulators
o Intracranial clips
o Intraorbital or intraocular metallic fragments
o Cochlear implants
o Ferromagnetic implants (e.g. thoracic implant for scoliosis)
o Inability to lie supine for 60 minutes
o Necessity of (continuous) daytime ventilation
o Scoliosis surgery
Healthy participants:
• Any known nerve or muscle disorder affecting the muscles measured.
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 | NL84168.091.23 |