Clinical, Immunological, Morphological and Genetic Characteristics of Patients With Dysferlinopathy in the RF

Dysferlinopathy Clinical Trial

— DYSF-RUS  

Official title:

Evaluation of Clinical, Immunological, Morphological, Molecular and Genetic Characteristics of Patients With Limb-girdle Muscular Dystrophy Type R2 (Type 2B) in the Russian Federation

Clinical Trial Details — Status: Enrolling by invitation

Administrative data

• NCT number: NCT04824040
• Other study ID #: DYSF-Observation (RUS)
• Status: Enrolling by invitation
• Start date: January 15, 2020
• Est. completion date: July 2024

Study information

• Verified date: July 2022
• Source: Human Stem Cell Institute, Russia
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational [Patient Registry]

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Enrolling by invitation
• Enrollment: 100
• Est. completion date: July 2024
• Est. primary completion date: February 25, 2024
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 85 Years

Eligibility

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).

Related Conditions & MeSH terms

• DMAT
• Dysferlinopathy
• LGMDR2
• Miyoshi Myopathy
• Muscular Diseases

Locations

Country	Name	City	State
Russian Federation	Human Stem Cells Institute	Moscow

Sponsors (2)

Lead Sponsor	Collaborator
Human Stem Cell Institute, Russia	Genotarget

Country where clinical trial is conducted

Russian Federation, 

References & Publications (2)

Khaiboullina SF, Martynova EV, Bardakov SN, Mavlikeev MO, Yakovlev IA, Isaev AA, Deev RV, Rizvanov AA. Serum Cytokine Profile in a Patient Diagnosed with Dysferlinopathy. Case Rep Med. 2017;2017:3615354. doi: 10.1155/2017/3615354. Epub 2017 Apr 13. — View Citation

Umakhanova ZR, Bardakov SN, Mavlikeev MO, Chernova ON, Magomedova RM, Akhmedova PG, Yakovlev IA, Dalgatov GD, Fedotov VP, Isaev AA, Deev RV. Corrigendum: Twenty-Year Clinical Progression of Dysferlinopathy in Patients from Dagestan. Front Neurol. 2017 Apr 18;8:145. doi: 10.3389/fneur.2017.00145. eCollection 2017. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	?linical status of patients with dysferlinopathy (MMT score)	Muscle strength will be assessed using MMT and will be expressed in points for each of the muscle groups assessed.	Through study completion at 24 months
Primary	?linical status of patients with dysferlinopathy ( North Star Assessment for dysferlinopathy)	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).	Through study completion at 24 months
Primary	?linical status of patients with dysferlinopathy (Hand Held Dynamometry).	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.	Through study completion at 24 months
Primary	?linical status of patients with dysferlinopathy (6-minute walk test)	The participant will be asked to complete maximal distance in 6 minet as quickly as safely possible and the time in seconds is recorded.	Through study completion at 24 months
Primary	Clinical blood test (level of hemoglobin)	Level of hemoglobin is planned to be assessed in patients with dysferlinopathy.	Through study completion at 24 months.
Primary	Clinical blood test. Level of hematocrit	Level of hematocrit (%) is planned to be assessed in patients with dysferlinopathy.	Through study completion at 24 months.
Primary	Clinical blood test. Level of RBC	Level of RBC is planned to be assessed in patients with dysferlinopathy.	Through study completion at 24 months.
Primary	Clinical blood test. Level of WBC	Level of WBC is planned to be assessed in patients with dysferlinopathy.	Through study completion at 24 months.
Primary	Clinical blood test. Levels of ESR	Levels of ESR (mm/h) is planned to be assessed in patients with dysferlinopathy.	Through study completion at 24 months.
Primary	Clinical blood test. Level of platelets	Level of platelets is planned to be assessed in patients with dysferlinopathy.	Through study completion at 24 months.
Primary	Biochemical blood test.	Levels of potassium (mmol/l) is planned to be assessed in patients with dysferlinopathy.	Through study completion at 24 months
Primary	Biochemical blood test. Level of sodium	Level of sodium (mmol/l) is planned to be assessed in patients with dysferlinopathy.	Through study completion at 24 months.
Primary	Biochemical blood test. Level of calcium	Level of calcium (mmol/l) is planned to be assessed in patients with dysferlinopathy.	Through study completion at 24 months.
Primary	Biochemical blood test. Level of creatinine	Level of creatinine (µmol/l) is planned to be assessed in patients with dysferlinopathy.	Through study completion at 24 months.
Primary	Biochemical blood test. Level of glucose	Level of glucose (mmol/l) is planned to be assessed in patients with dysferlinopathy.	Through study completion at 24 months.
Primary	Biochemical blood test. Level of uric acid	Level of uric acid (µmol/l) is planned to be assessed in patients with dysferlinopathy.	Through study completion at 24 months.
Primary	Biochemical blood test. Level of urea	Level of urea (mmol/l) is planned to be assessed in patients with dysferlinopathy.	Through study completion at 24 months.
Primary	Biochemical blood test. Level of ALT	Level of ALT (U/l) is planned to be assessed in patients with dysferlinopathy.	Through study completion at 24 months.
Primary	Biochemical blood test. Level of AST	Level of AST (U/l) is planned to be assessed in patients with dysferlinopathy.	Through study completion at 24 months.
Primary	Biochemical blood test. Level of total protein	Level of total protein (g/l) is planned to be assessed in patients with dysferlinopathy.	Through study completion at 24 months.
Primary	Biochemical blood test. Level of CPK	Level of CPK (U/l) is planned to be assessed in patients with dysferlinopathy.	Through study completion at 24 months.
Primary	Biochemical blood test. Level of triglycerides	Level of triglycerides (mmol/l) is planned to be assessed in patients with dysferlinopathy.	Through study completion at 24 months.
Primary	Biochemical blood test. Level of CRP	Level of CRP (mg/l) is planned to be assessed in patients with dysferlinopathy.	Through study completion at 24 months.
Primary	Blood cytokine levels in subjects with dysferlinopathy and healthy volunteers.	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-?, IL-1ß, 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-1a, MIP-1ß,PDGF-BB, RANTES, TNF-a, VEGF.	Through study completion at 24 months
Primary	Autoantibodies in patients with dysferlinopathy.	Assessment of antibod? level against skeletal muscle antigens; an antinuclear factor (ANA), an extractable nuclear antigen.	Through study completion at 24 months
Primary	Muscle MRI in patients with dysferlinopathy.	To characterize muscle involvement based on MRI results; To evaluate the progression of muscle involvement based on repeated MRI once year;	Through study completion at 24 months.
Primary	Subpopulation compositions of T-lymphocytes in subjects with dysferlinopathy.	• To characterize changes in subpopulation compositions of T-lymphocytes in %.	Through study completion at 24 months
Primary	Subpopulation compositions of B-lymphocytes in subjects with dysferlinopathy.	• To characterize changes in subpopulation compositions of B-lymphocytes in %.	Through study completion at 24 months
Primary	Subpopulation compositions of phagocytic activity of leukocytes in subjects with dysferlinopathy (NBT test)	• To characterize changes in phagocytic activity of leukocytes (NBT test in CU).	Through study completion at 24 months
Primary	Subpopulation compositions of phagocytic activity of leukocytes in subjects with dysferlinopathy.	• To characterize changes in phagocytic activity of leukocytes (a phagocyte number in CU).	Through study completion at 24 months
Primary	Subpopulation compositions of phagocytic activity of leukocytes in subjects with dysferlinopathy (lysosomal-cation test).	• To characterize changes in phagocytic activity of leukocytes (lysosomal-cation test in CU).	Through study completion at 24 months
Primary	Subpopulation compositions of phagocytic activity of leukocytes (a phagocytic index) in subjects with dysferlinopathy.	• To characterize changes in phagocytic activity of leukocytes (a phagocytic index).	Through study completion at 24 months
Primary	Gait pattern and balance characteristics in patients with limb-girdle muscular dystrophy R2.	To determine a gait pattern characteristics in patients with limb-girdle muscular dystrophy R2 using electrophysiological techniques (Neurosoft Gait Assessment System "STEDIS").	Through study completion at 24 months.
Primary	Cardiac function (assessed by Echocardiography). LV	The absolute and relative sizes of the left ventricle (LV) index will be determined.	Through study completion at 24 months.
Primary	Cardiac function (assessed by Echocardiography). LV mass	The absolute and relative sizes of the LV mass index will be determined.	Through study completion at 24 months.
Primary	Cardiac function (assessed by Echocardiography). Myocardium mass	The absolute and relative sizes of the myocardium mass index will be determined.	Through study completion at 24 months.
Primary	Cardiac function (assessed by Echocardiography). RV	The absolute and relative sizes of the right ventricle (RV) index will be determined.	Through study completion at 24 months.
Primary	Cardiac function (assessed by MRI scan with a gadolinium-based contrast agent). Volumetric evaluation of LV mass	Volumetric evaluation of LV mass by manual tracing will be perform. An MRI of the heart will assess fibrosis.	Through study completion at 24 months.
Primary	Cardiac function (assessed by Echocardiography). LA	The absolute and relative sizes of the left atrium (LA) index will be determined	Through study completion at 24 months.
Primary	Cardiac function (assessed by Electrocardiography). Outcome 13	To assess rhythm characteristic, P-wave, QRS, T-wave duration; PR, RR, QT intervals; PR, ST segments.	Through study completion at 24 months.
Primary	Cardiac function (assessed by MRI scan with a gadolinium-based contrast agent). Volumetric evaluation of EF	Volumetric evaluation of EF by manual tracing will be performed.	Through study completion at 24 months.
Primary	Cardiac function (assessed by MRI scan with a gadolinium-based contrast agent).	Volumetric evaluation of volume by manual tracing will be performed.	Through study completion at 24 months.
Primary	Morphological muscle study	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.	Through study completion at 24 months.