Clinical trial NCT04824040: Clinical, Immunological, Morphological and Genetic Characteristics of Patients With Dysferlinopathy in the RF
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
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Dysferlinopathy
Miyoshi Myopathy
LGMDR2
DMAT
Keywords: LGMDR2
Miyoshi Myopathy
Dysferlinopathy
DYSF
DMAT
Lead sponsor: Human Stem Cell Institute, Russia
Sponsor class: OTHER
Collaborators: name: Genotarget
First posted: 2021-04-01
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Study participants will be identified through self-selection and direct recruitment options. Participants will be identified from the population of individuals who are followed at the neuromuscular clinics. Participants will also be solicited from the DYSF Russian registry.

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.

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).

Primary outcomes:
measure: Сlinical status of patients with dysferlinopathy (MMT score)
timeFrame: Through study completion at 24 months
measure: Сlinical status of patients with dysferlinopathy ( North Star Assessment for dysferlinopathy)
timeFrame: Through study completion at 24 months
measure: Сlinical status of patients with dysferlinopathy (Hand Held Dynamometry).
timeFrame: Through study completion at 24 months
measure: Сlinical status of patients with dysferlinopathy (6-minute walk test)
timeFrame: Through study completion at 24 months
measure: Clinical blood test (level of hemoglobin)
timeFrame: Through study completion at 24 months.
measure: Clinical blood test. Level of hematocrit
timeFrame: Through study completion at 24 months.
measure: Clinical blood test. Level of RBC
timeFrame: Through study completion at 24 months.
measure: Clinical blood test. Level of WBC
timeFrame: Through study completion at 24 months.
measure: Clinical blood test. Levels of ESR
timeFrame: Through study completion at 24 months.
measure: Clinical blood test. Level of platelets
timeFrame: Through study completion at 24 months.
measure: Biochemical blood test.
timeFrame: Through study completion at 24 months
measure: Biochemical blood test. Level of sodium
timeFrame: Through study completion at 24 months.
measure: Biochemical blood test. Level of calcium
timeFrame: Through study completion at 24 months.
measure: Biochemical blood test. Level of creatinine
timeFrame: Through study completion at 24 months.
measure: Biochemical blood test. Level of glucose
timeFrame: Through study completion at 24 months.
measure: Biochemical blood test. Level of uric acid
timeFrame: Through study completion at 24 months.
measure: Biochemical blood test. Level of urea
timeFrame: Through study completion at 24 months.
measure: Biochemical blood test. Level of ALT
timeFrame: Through study completion at 24 months.
measure: Biochemical blood test. Level of AST
timeFrame: Through study completion at 24 months.
measure: Biochemical blood test. Level of total protein
timeFrame: Through study completion at 24 months.
measure: Biochemical blood test. Level of CPK
timeFrame: Through study completion at 24 months.
measure: Biochemical blood test. Level of triglycerides
timeFrame: Through study completion at 24 months.
measure: Biochemical blood test. Level of CRP
timeFrame: Through study completion at 24 months.
measure: Blood cytokine levels in subjects with dysferlinopathy and healthy volunteers.
timeFrame: Through study completion at 24 months
measure: Autoantibodies in patients with dysferlinopathy.
timeFrame: Through study completion at 24 months
measure: Muscle MRI in patients with dysferlinopathy.
timeFrame: Through study completion at 24 months.
measure: Subpopulation compositions of T-lymphocytes in subjects with dysferlinopathy.
timeFrame: Through study completion at 24 months
measure: Subpopulation compositions of B-lymphocytes in subjects with dysferlinopathy.
timeFrame: Through study completion at 24 months
measure: Subpopulation compositions of phagocytic activity of leukocytes in subjects with dysferlinopathy (NBT test)
timeFrame: Through study completion at 24 months
measure: Subpopulation compositions of phagocytic activity of leukocytes in subjects with dysferlinopathy.
timeFrame: Through study completion at 24 months
measure: Subpopulation compositions of phagocytic activity of leukocytes in subjects with dysferlinopathy (lysosomal-cation test).
timeFrame: Through study completion at 24 months
measure: Subpopulation compositions of phagocytic activity of leukocytes (a phagocytic index) in subjects with dysferlinopathy.
timeFrame: Through study completion at 24 months
measure: Gait pattern and balance characteristics in patients with limb-girdle muscular dystrophy R2.
timeFrame: Through study completion at 24 months.
measure: Cardiac function (assessed by Echocardiography). LV
timeFrame: Through study completion at 24 months.
measure: Cardiac function (assessed by Echocardiography). LV mass
timeFrame: Through study completion at 24 months.
measure: Cardiac function (assessed by Echocardiography). Myocardium mass
timeFrame: Through study completion at 24 months.
measure: Cardiac function (assessed by Echocardiography). RV
timeFrame: Through study completion at 24 months.
measure: Cardiac function (assessed by MRI scan with a gadolinium-based contrast agent). Volumetric evaluation of LV mass
timeFrame: Through study completion at 24 months.
measure: Cardiac function (assessed by Echocardiography). LA
timeFrame: Through study completion at 24 months.
measure: Cardiac function (assessed by Electrocardiography). Outcome 13
timeFrame: Through study completion at 24 months.
measure: Cardiac function (assessed by MRI scan with a gadolinium-based contrast agent). Volumetric evaluation of EF
timeFrame: Through study completion at 24 months.
measure: Cardiac function (assessed by MRI scan with a gadolinium-based contrast agent).
timeFrame: Through study completion at 24 months.
measure: Morphological muscle study
timeFrame: Through study completion at 24 months.
Secondary outcomes:
Other outcomes:
Locations:
city: Moscow
country: Russian Federation
facility: Human Stem Cells Institute
Study officials:
affiliation: HSCI, Russia
name: Roman Deev, PhD
role: STUDY_CHAIR
References:
citation: 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.
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.