Evaluation of Clinical, Immunological, Morphological, Molecular and Genetic Characteristics of Patients With Limb-girdle Muscular Dystrophy Type R2 (Type 2B) in the Russian Federation
Overview
- Phase
- Not Applicable
- Intervention
- Not specified
- Conditions
- Dysferlinopathy
- Sponsor
- Artgen Biotech
- Enrollment
- 100
- Locations
- 1
- Primary Endpoint
- Сlinical status of patients with dysferlinopathy (MMT score)
- Status
- Enrolling By Invitation
- Last Updated
- 10 months ago
Overview
Brief Summary
To evaluate specific characteristics of phenotype, immune status, molecular and genetic as well as morphological characteristics of adult patients with limb-girdle muscular dystrophy R2 in various regions of the Russian Federation.
Detailed Description
A single-center, cohort clinical study. Subjects of both sexes aged 18 to 65 inclusive with genetically confirmed diagnosis of limb-girdle muscular dystrophy type R2, who have signed the written informed consent form for this study. The control and case groups should be age- and gender-matched. Study Objectives: * To evaluate a clinical status of a subject (MMT score; 6-minute walk test; North Star Assessment for dysferlinopathy (NSAD)); * To assess blood biochemistry; * To characterize muscle involvement based on MRI results; * To evaluate the progression of muscle involvement based on repeated MRI; * To assess cardiac function with ECG, EchoCG and MRI; * To determine a gait pattern and balance characteristics in patients with limb-girdle muscular dystrophy using electrophysiological techniques (Neurosoft Gait Assessment System Steadys; stabilometrics and plantography with "SIDAS"); * To characterize changes in subpopulation compositions of T- and B-lymphocytes, phagocytic activity of leukocytes (a phagocytic index, a phagocyte number, an index of phagocytosis completeness, lysosomal-cation and NBT tests); * To assess average blood cytokine levels in subjects with limb-girdle muscular dystrophy (type R2) in various regions of the Russian Federation; * To assess average blood cytokine levels in healthy subjects from various regions of the RF; * To analyze the relationship between blood cytokine levels and the presence of a mutation in the dysferlin gene; * To study the expression (immunohistochemistry and western-blotting) and distribution of dysferlin in impaired muscles of subjects with LGMDR2. The clinical study includes the stages as follows: 1. Subject enrollment - 24 months 2. Data collection and analysis - 12 months 3. Study Report - 30 days.
Investigators
Eligibility Criteria
Inclusion Criteria
- •18 to 85 (inclusive) years-old subjects of both sexes;
- •A signed written informed consent form;
- •Genetically confirmed diagnosis of limb-girdle muscular dystrophy (type 2B) (a case group)
Exclusion Criteria
- •A subject who is an investigator, study assistant, study coordinator and a member of the other personnel indirectly or directly associated with the conduct of the study;
- •Acute medical conditions associated with visceral dysfunction, life-threatening conditions which occurred less than 6 months prior to enrollment into the study such as acute cardiac, renal, hepatic insufficiency, myocardial infarction or an acute cerebrovascular accident (stroke) as well as infectious diseases;
- •Excessive alcohol consumption (\> 20 g/day).
Outcomes
Primary Outcomes
Сlinical status of patients with dysferlinopathy (MMT score)
Time Frame: Through study completion at 24 months
Muscle strength will be assessed using MMT and will be expressed in points for each of the muscle groups assessed.
Сlinical status of patients with dysferlinopathy (6-minute walk test)
Time Frame: Through study completion at 24 months
The participant will be asked to complete maximal distance in 6 minet as quickly as safely possible and the time in seconds is recorded.
Сlinical status of patients with dysferlinopathy (Hand Held Dynamometry).
Time Frame: Through study completion at 24 months
Hand held dynamometry using the MicroFET2 myometer will be utilized to capture isometric muscle strength. Maximum strength in kilograms will be reported for each muscle group.
Clinical blood test. Level of RBC
Time Frame: Through study completion at 24 months.
Level of RBC is planned to be assessed in patients with dysferlinopathy.
Biochemical blood test.
Time Frame: Through study completion at 24 months
Levels of potassium (mmol/l) is planned to be assessed in patients with dysferlinopathy.
Biochemical blood test. Level of creatinine
Time Frame: Through study completion at 24 months.
Level of creatinine (μmol/l) is planned to be assessed in patients with dysferlinopathy.
Biochemical blood test. Level of ALT
Time Frame: Through study completion at 24 months.
Level of ALT (U/l) is planned to be assessed in patients with dysferlinopathy.
Blood cytokine levels in subjects with dysferlinopathy and healthy volunteers.
Time Frame: Through study completion at 24 months
* To assess average blood cytokine levels in subjects with dysferlinopathy in various regions of the Russian Federation; * To assess average blood cytokine levels in healthy subjects. Blood serum cytokine profiling will be performed with the use of the multiparameter fluorescent diagnostic system Luminex 200 and the Bio-Plex Pro Human 27-Plex Panel (Bio-Rad, Hercules, USA) in accordance with the manufacturer's instructions. The data obtained will be processed with the use of MasterPlex CT control and MasterPlex QT analysis software (Hitachi Software, San Bruno, USA). The following cytokine Levels will be assessed in the study:FGF2, Eotaxin,G-CSF, GM-CSF, IFN-γ, IL-1β, 1IL-1ra, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-9, IL-10, IL-12 p70, IL-13, IL-15, IL-17, IP-10, MCP-1/MCAF, MIP-1α, MIP-1β,PDGF-BB, RANTES, TNF-α, VEGF.
Subpopulation compositions of T-lymphocytes in subjects with dysferlinopathy.
Time Frame: Through study completion at 24 months
• To characterize changes in subpopulation compositions of T-lymphocytes in %.
Subpopulation compositions of phagocytic activity of leukocytes (a phagocytic index) in subjects with dysferlinopathy.
Time Frame: Through study completion at 24 months
• To characterize changes in phagocytic activity of leukocytes (a phagocytic index).
Clinical blood test. Level of hematocrit
Time Frame: Through study completion at 24 months.
Level of hematocrit (%) is planned to be assessed in patients with dysferlinopathy.
Clinical blood test. Level of platelets
Time Frame: Through study completion at 24 months.
Level of platelets is planned to be assessed in patients with dysferlinopathy.
Biochemical blood test. Level of sodium
Time Frame: Through study completion at 24 months.
Level of sodium (mmol/l) is planned to be assessed in patients with dysferlinopathy.
Biochemical blood test. Level of glucose
Time Frame: Through study completion at 24 months.
Level of glucose (mmol/l) is planned to be assessed in patients with dysferlinopathy.
Clinical blood test (level of hemoglobin)
Time Frame: Through study completion at 24 months.
Level of hemoglobin is planned to be assessed in patients with dysferlinopathy.
Clinical blood test. Levels of ESR
Time Frame: Through study completion at 24 months.
Levels of ESR (mm/h) is planned to be assessed in patients with dysferlinopathy.
Subpopulation compositions of phagocytic activity of leukocytes in subjects with dysferlinopathy (NBT test)
Time Frame: Through study completion at 24 months
• To characterize changes in phagocytic activity of leukocytes (NBT test in CU).
Cardiac function (assessed by Electrocardiography). Outcome 13
Time Frame: Through study completion at 24 months.
To assess rhythm characteristic, P-wave, QRS, T-wave duration; PR, RR, QT intervals; PR, ST segments.
Cardiac function (assessed by MRI scan with a gadolinium-based contrast agent). Volumetric evaluation of EF
Time Frame: Through study completion at 24 months.
Volumetric evaluation of EF by manual tracing will be performed.
Сlinical status of patients with dysferlinopathy ( North Star Assessment for dysferlinopathy)
Time Frame: Through study completion at 24 months
North Star Assessment for Dysferlinopathy (NSAD) is a functional scale that will be used to measure motor performance in individuals with dysferlinopathy (includes 29 items).
Biochemical blood test. Level of calcium
Time Frame: Through study completion at 24 months.
Level of calcium (mmol/l) is planned to be assessed in patients with dysferlinopathy.
Biochemical blood test. Level of uric acid
Time Frame: Through study completion at 24 months.
Level of uric acid (μmol/l) is planned to be assessed in patients with dysferlinopathy.
Biochemical blood test. Level of CRP
Time Frame: Through study completion at 24 months.
Level of CRP (mg/l) is planned to be assessed in patients with dysferlinopathy.
Muscle MRI in patients with dysferlinopathy.
Time Frame: Through study completion at 24 months.
* To characterize muscle involvement based on MRI results; * To evaluate the progression of muscle involvement based on repeated MRI once year;
Clinical blood test. Level of WBC
Time Frame: Through study completion at 24 months.
Level of WBC is planned to be assessed in patients with dysferlinopathy.
Biochemical blood test. Level of urea
Time Frame: Through study completion at 24 months.
Level of urea (mmol/l) is planned to be assessed in patients with dysferlinopathy.
Biochemical blood test. Level of AST
Time Frame: Through study completion at 24 months.
Level of AST (U/l) is planned to be assessed in patients with dysferlinopathy.
Biochemical blood test. Level of total protein
Time Frame: Through study completion at 24 months.
Level of total protein (g/l) is planned to be assessed in patients with dysferlinopathy.
Biochemical blood test. Level of CPK
Time Frame: Through study completion at 24 months.
Level of CPK (U/l) is planned to be assessed in patients with dysferlinopathy.
Subpopulation compositions of phagocytic activity of leukocytes in subjects with dysferlinopathy (lysosomal-cation test).
Time Frame: Through study completion at 24 months
• To characterize changes in phagocytic activity of leukocytes (lysosomal-cation test in CU).
Cardiac function (assessed by Echocardiography). Myocardium mass
Time Frame: Through study completion at 24 months.
The absolute and relative sizes of the myocardium mass index will be determined.
Cardiac function (assessed by Echocardiography). LA
Time Frame: Through study completion at 24 months.
The absolute and relative sizes of the left atrium (LA) index will be determined
Biochemical blood test. Level of triglycerides
Time Frame: Through study completion at 24 months.
Level of triglycerides (mmol/l) is planned to be assessed in patients with dysferlinopathy.
Autoantibodies in patients with dysferlinopathy.
Time Frame: Through study completion at 24 months
Assessment of antibodу level against skeletal muscle antigens; an antinuclear factor (ANA), an extractable nuclear antigen.
Subpopulation compositions of B-lymphocytes in subjects with dysferlinopathy.
Time Frame: Through study completion at 24 months
• To characterize changes in subpopulation compositions of B-lymphocytes in %.
Subpopulation compositions of phagocytic activity of leukocytes in subjects with dysferlinopathy.
Time Frame: Through study completion at 24 months
• To characterize changes in phagocytic activity of leukocytes (a phagocyte number in CU).
Cardiac function (assessed by MRI scan with a gadolinium-based contrast agent).
Time Frame: Through study completion at 24 months.
Volumetric evaluation of volume by manual tracing will be performed.
Gait pattern and balance characteristics in patients with limb-girdle muscular dystrophy R2.
Time Frame: Through study completion at 24 months.
To determine a gait pattern characteristics in patients with limb-girdle muscular dystrophy R2 using electrophysiological techniques (Neurosoft Gait Assessment System "STEDIS").
Cardiac function (assessed by Echocardiography). LV
Time Frame: Through study completion at 24 months.
The absolute and relative sizes of the left ventricle (LV) index will be determined.
Cardiac function (assessed by Echocardiography). LV mass
Time Frame: Through study completion at 24 months.
The absolute and relative sizes of the LV mass index will be determined.
Cardiac function (assessed by Echocardiography). RV
Time Frame: Through study completion at 24 months.
The absolute and relative sizes of the right ventricle (RV) index will be determined.
Cardiac function (assessed by MRI scan with a gadolinium-based contrast agent). Volumetric evaluation of LV mass
Time Frame: Through study completion at 24 months.
Volumetric evaluation of LV mass by manual tracing will be perform. An MRI of the heart will assess fibrosis.
Morphological muscle study
Time Frame: Through study completion at 24 months.
If it was necessary to confirm the causation of mutations in the dysferlin gene, the patients underwent muscle biopsy. To study the expression (immunohistochemistry and western-blotting) and distribution of dysferlin in impaired muscles of subjects with LGMDR2.