Clinical Trial Details
— Status: Not yet recruiting
Administrative data
| NCT number |
NCT06390566 |
| Other study ID # |
APHP230610 |
| Secondary ID |
|
| Status |
Not yet recruiting |
| Phase |
|
| First received |
|
| Last updated |
|
| Start date |
April 30, 2024 |
| Est. completion date |
April 30, 2026 |
Study information
| Verified date |
October 2023 |
| Source |
Assistance Publique - Hôpitaux de Paris |
| Contact |
Edoardo Malfatti, Professor |
| Phone |
0033149814496 |
| Email |
edoardo.malfatti[@]aphp.fr |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Observational
|
Clinical Trial Summary
Limb girdle muscular dystrophies were originally defined as a postnatal progressive muscle
disease, which begins and primarily affects the pelvic and scapular muscles.
Description:
Intro:
Limb girdle muscular dystrophies were originally defined as a postnatal progressive muscle
disease, which begins and primarily affects the pelvic and scapular muscles.
To be considered a form of limb-girdle muscular dystrophy, according to the European
Neuromuscular Center, the condition must be described in at least two unrelated families with
affected individuals achieving independent walking, must have elevated serum creatine kinase
activity, must demonstrate degenerative changes on muscle imagery over the course of the
disease, and must exhibit dystrophic changes on muscle histology, ultimately leading to
end-stage pathology for the most affected muscles.
They are classified into dominant forms (LGMD 1, old nomenclature; LGMD D, new nomenclature)
and recessive forms (LGMD 2, old nomenclature; LGMD R new nomenclature). Recessive forms
predominate in terms of number of subtypes and individual prevalence, with regional
variations due to founder effects in some cases (Murphy et al, 2015).
Individually, distinct subtypes of LGMD are relatively rare; however, as a group, the minimum
prevalence of LGMD is probably between 2.27 per 100,000 and 10 per 100,000. In Europe and the
United States, calpainopathies, also called LGMD R1 or LGMD-2A (OMIM 253600 ), are the most
common of the different types of LGMD, accounting for up to 30% of all cases of recessive
LGMD.
There is currently no cure for the disease, the management of which is still based on
rehabilitation therapies and the prevention of other complications. The development of new
therapeutic approaches, in particular gene therapies, requires the best possible
characterization of the natural history of the disease, in order to identify the patients
with the most unfavorable evolutions and to characterize their chronology, and in order to
identify the clinical and paraclinical parameters that are most sensitive to change, allowing
the effectiveness of new treatments to be better assessed in future randomized trials.
However, there are currently no or few recent data from prospective cohorts representative of
the population of interest and including detailed phenotyping data such as muscle MRI.
Hypothesis/Objective
Primary objective :
The main objective of this study is to identify and quantify the loss of strength of the
muscle groups of the upper (e.g.: raising the arms, lifting a weight, etc.) and lower (e.g.:
walking, standing, etc.) limbs over a period of time. of 2 years in 25 patients suffering
from LGMD2A already followed at the Reference Center for Neuromuscular Diseases of Mondor
Hospital.
Secondary objectives:
- Define the evaluation criteria (scales, measurements) capable of defining the
therapeutic response after the gene therapy clinical trial,
- Describe the loss of muscle functions (inability to raise the arms, wheelchair) and
muscle weakness of the upper and lower limbs,
- Identify and monitor imaging and laboratory analysis parameters which are indicators of
the progression of the disease leading to muscle deficit.
Method
Primary evaluation criteria:
Assessment of motor function • Assessment of change from baseline in motor function assessed
with the North Star Assessment (NSAD) scale score for Limb Girdle Muscular Dystrophies.
Secondary evaluation criteria:
Assessment of motor function of the upper and lower limbs
- Assessment of motor function of the upper and lower limbs with the Brooke and Vignos
scales Assessment of muscle strength
- 1) Isometric manual muscular assessment
- 2) Quantitative isometric muscle evaluations (Quantitative Muscle Testing (QMT))
- Myotools and manual dynamometer (Hand Held Dynamometry (HHD)) Assessment of motor
function of the upper limbs
- Assessment of the upper limbs using the PUL (Performance of the Upper Limb) assessment
tool, filmed version using 3 cameras Assessment of movement activity Walking Ability
Using the FeetMe® Monitor Muscle MRI
- Muscle anatomy (volume, fatty infiltration)
- Modified Mercuri Score (mMS) to measure fat splitting Laboratory analysis
Biobank samples:
- Blood sampling for hematology analyzes
- Blood sampling for biochemistry analysis (CK)
- Blood sampling for coagulation analysis Quality of life questionnaire
- Quality of life questionnaire for genetic neuromuscular diseases (gNMD) and ACTIVLIM
questionnaire
Conclusion The overall objective of the analyzes planned in this study is to characterize
disease progression in patients with LGMD2A over a period of up to 24 months. The choice of a
study duration of 24 months is linked to the fact that over a shorter period significant
changes would not have been observable and a longer duration would have greatly increased the
burden and scale of the study at the time. logistical level. It is important to develop
detailed natural history data to better understand the driving course of the disease and
validate assays as well as clinical outcome measures to define relevant endpoints for future
clinical trials.
