Ignite Creation Date:
2024-05-06 @ 8:27 PM
Last Modification Date:
2024-10-26 @ 3:28 PM
Study NCT ID:
NCT06390566
Status:
NOT_YET_RECRUITING
Last Update Posted:
2024-04-30
First Post:
2024-04-25
Brief Title:
Evolution of the Functional and Muscular State of Patients With Muscular Dystrophy 2A Belts
Sponsor:
Assistance Publique - Hôpitaux de Paris
Organization:
Assistance Publique - Hôpitaux de Paris
Study Overview
Official Title:
Evolution of the Functional and Muscular State and Quality of Life of Patients With Limb-girdle Muscular Dystrophy 2A CALNATHIS Prospective Cohort Study
Status:
NOT_YET_RECRUITING
Status Verified Date:
2023-10
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
CALNATHIS
Brief Summary:
Limb girdle muscular dystrophies were originally defined as a postnatal progressive muscle disease which begins and primarily affects the pelvic and scapular muscles
Detailed 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 227 per 100000 and 10 per 100000 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
HypothesisObjective
Primary objective
The main objective of this study is to identify and quantify the loss of strength of the muscle groups of the upper eg raising the arms lifting a weight etc and lower eg 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
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 227 per 100000 and 10 per 100000 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
HypothesisObjective
Primary objective
The main objective of this study is to identify and quantify the loss of strength of the muscle groups of the upper eg raising the arms lifting a weight etc and lower eg 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
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None