The primary objective is to develop a disease model predicting clinical meaningful changes based on a combination of results of tests on clinical function, muscle MRI, echocardiography and circulating biomarkers applicable in various stages of…
ID
Source
Brief title
Condition
- Neuromuscular disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The main study endpoint is a model to predict the disease course of individual
BMD patients based on the following parameters: clinical parameters (e.g. loss
of ambulation), functional parameters (e.g. North Star Ambulatory assessment,
strength measures), pulmonary parameters (e.g. forced vital capacity), cardiac
parameters (e.g. left ventricular ejection fraction), muscle MRI
characteristics (e.g. fat fraction) and biomarkers in serum (e.g.
creatine/creatinine ratio).
Secondary outcome
Main clinical parameters at each time point:
- Weight (kg)
- Height (meters)
- Blood pressure (mmHg)
- Heart rate (beats/min)
- Ulna length (cm)
- ACTIVLIM and the PROM upper limb DMD
- Loss of ambulation (date, whenever applicable)
- Other clinical endpoints (first symptoms, diagnosis, use of walking aids,
occasional use of wheelchair, loss of function arm to mouth, start use of
respiratory support, cardiomyopathy, start use of cardiac support; date,
whenever applicable)
Main pulmonary parameters at each time point:
- Forced Vital Capacity (FVC) in percentage
- Forced Expiratory Volume in 1 second (FEV1) in percentage
- Peak Cough Flow (PCF) in percentage
Main functional parameters at each time point:
- North Star Ambulatory Assessment (NSAA) in points
- Timed tests (6 minute walk test (meters), 10 meter run test (seconds), time
to rise from floor (seconds), time to climb 4 stairs (seconds), time to descend
4 stairs (seconds))
- Performance of the Upper Limb (PUL) 2.0 in points.
- Pinch strength (kg), grip strength (kg) measured using Myopinch and MyoGrip.
- Strength (kg) of at minimum: both flexion and extension of knee hip and elbow
Main cardiac parameters at each time point:
- Left ventricular (LV) ejection fraction (LVEF) in percentage
- Left ventricular end diastolic volume (LVEDV) in ml
- Left ventricular end systolic volume (LVESV) in ml
- Left ventricular global longitudinal strain (LVGLS) in percentage
Main qMRI characteristics at each time point
- Multiple MRI parameters including muscle volume, fat fraction and DTI
parameters.
Main parameters of muscle biopsy:
- Fibre size and other structural parameters
- Dystrophin quantification
Background summary
Becker muscular dystrophy (BMD) is a rare X-linked recessive disorder caused by
a mutation in the dystrophin gene resulting in progressive muscle weakness.
Cardiac involvement occurs in around 70% of the BMD patients and in some cases
lung function is affected. Disease progression is slow making chances of
observing clinically relevant end points during a clinical trial low. This in
combination with the rarity of the disease and the large heterogeneity in
symptoms makes research for possible therapies challenging. A model to predict
disease progression based on biomarkers could potentially provide a solution to
this problem in two ways. Firstly, it would enable researchers to select the
patients in whom measurable disease progression is expected, thereby increase
the chances of observing clinical endpoints within the duration of a trial.
Secondly, this model could potentially be used to compare the predicted disease
progression at the beginning of a trial with the observed progression at the
end of a trial. This difference can then be used as a measure for the effect of
the intervention.
Previous research has identified several potential serum and MRI biomarkers. In
2014, a 4 year natural history study was initiated at the LUMC collecting
biomarkers as well as clinical parameters such as strength measures and the 6
minute walking distance. Preliminary data indicated that a longer follow-up and
expansion of the cohort to include a larger disease spectrum are essential to
be able to predict long term changes in BMD and to facilitate trial readiness.
Therefore, this study aims to extend the follow-up in this cohort and expand
the cohort also including children.
Study objective
The primary objective is to develop a disease model predicting clinical
meaningful changes based on a combination of results of tests on clinical
function, muscle MRI, echocardiography and circulating biomarkers applicable in
various stages of disease in BMD patients.
The secondary objective is to link biomarkers to biology in BMD patients by
spatial transcriptomics and quantitative muscle MRI.
Study design
Prospective observational cohort study
Study burden and risks
Patients will not benefit directly from participating in this study, but will
contribute to the knowledge on BMD of which they may benefit in the future. The
burden consists of 4 annual visits lasting a complete day. For patients under
treatment at the LUMC, the study visits will be combined the regular follow-up
as much as possible.
For the vast majority of the investigations in this protocol, there is no risk.
A MRI maybe considered unpleasant, for which there is an opt-out possibility.
Muscle biopsy may result in an hematoma and/or a 1-2 cm scar, for which in
general no treatment is required. Also for muscle biopsy, there is an opt-out
possibility.
Albinusdreef 2
Leiden 2333ZA
NL
Albinusdreef 2
Leiden 2333ZA
NL
Listed location countries
Age
Inclusion criteria
BMD patient cohort:
• Male
• Confirmation of diagnosis of BMD by DNA analysis
• Age >=5 years
In order to be eligible to partake in the muscle biopsy part of this study, the
following additional inclusion criteria apply:
• Age >= 18 years
BMD trial participants cohort:
• Male
• Confirmation of diagnosis of BMD by DNA analysis
• Age >=5 years
• Inclusion in the phase II study of EDG-5506 in BMD (P22-064)
Healthy controls:
• Male
• Age >=5 years
In order to be eligible to partake in the muscle biopsy part of this study, the
following additional inclusion criteria apply:
• Age >= 18 years
Exclusion criteria
Patients will not undergo MRI or muscle biopsy if they have contraindication
for the MRI (such as a metal implant) or muscle biopsy (such as use of
anticoagulation) respectively. If this is the case, it is still possible to
partake in the other parts of this study.
Design
Recruitment
metc-ldd@lumc.nl
metc-ldd@lumc.nl
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 | NL77823.058.22 |