Clinical, Immunological, Morphological and Genetic Characteristics of Patients With Dysferlinopathy (LGMD R2) in the RF

Официальное название

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

Обзор

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.

Подробное описание

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.

Первичные конечные точки

• Сlinical status of patients with dysferlinopathy (MMT score) [Срок оценки: Through study completion at 24 months]
• Сlinical status of patients with dysferlinopathy ( North Star Assessment for dysferlinopathy) [Срок оценки: Through study completion at 24 months]
• Сlinical status of patients with dysferlinopathy (Hand Held Dynamometry). [Срок оценки: Through study completion at 24 months]
• Сlinical status of patients with dysferlinopathy (6-minute walk test) [Срок оценки: Through study completion at 24 months]
• Clinical blood test (level of hemoglobin) [Срок оценки: Through study completion at 24 months.]
• Clinical blood test. Level of hematocrit [Срок оценки: Through study completion at 24 months.]
• Clinical blood test. Level of RBC [Срок оценки: Through study completion at 24 months.]
• Clinical blood test. Level of WBC [Срок оценки: Through study completion at 24 months.]
• Clinical blood test. Levels of ESR [Срок оценки: Through study completion at 24 months.]
• Clinical blood test. Level of platelets [Срок оценки: Through study completion at 24 months.]

Критерии участия

Критерии включения

• 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)

Критерии исключения

• 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).

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Да

Дизайн исследования

Модель наблюдения

Когортное

Центры проведения

Россия · 1 центр

• Human Stem Cells Institute — Moscow

Публикации

• Umakhanova ZR, Bardakov SN, Mavlikeev MO, Chernova ON, Magomedova RM, Akhmedova PG, Yakovlev IA, Dalgatov GD, Fedotov VP, Isaev AA, Deev RV. Twenty-Year Clinical Progression of Dysferlinopathy in Patients from Dagestan. Front Neurol. 2017 Mar 8;8:77. doi: 10.3389/fneur.2017.00077. eCollection 2017. PMID 28337173
• 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. PMID 28487742
• Bardakov SN, Deev RV, Tsargush VA, Kaimonov VS, Musatova EV, Blagodatskikh KA, Tveleneva AA, Sofronova YV, Suslov VM, Carlier PG, Kurbatov SA, Yakovlev IA, Umakhanova ZR, Isaev AA. Asymptomatic and oligosymptomatic states of dysferlinopathy. J Neuromuscul Dis. 2024 Nov;11(6):1283-1294. doi: 10.1177/22143602241289227. Epub 2024 Dec 8. PMID 39973465
• Bardakov SN, Deev RV, Isaev capital A, Cyrilliccapital A, Cyrillic, Khromov-Borisov NN, Kopylov ED, Savchuk capital EM, CyrillicR, Pushkin MS, Presnyakov EV, Magomedova RM, Achmedova PG, Umakhanova ZR, Kaimonov VS, Musatova EV, Blagodatskikh Kcapital A, Cyrillic, Tveleneva Acapital A, Cyrillic, Sofronova YV, Yakovlev IA. Genetic screening of an endemic mutation in the DYSF gene in an isolated, mou PMID 37553796
• Bardakov SN, Titova AA, Nikitin SS, Nikitins V, Sokolova MO, Tsargush VA, Yuhno EA, Vetrovoj OV, Carlier PG, Sofronova YV, Isaev capital A, Cyrilliccapital A, Cyrillic, Deev RV. Miyoshi myopathy associated with spine rigidity and multiple contractures: a case report. BMC Musculoskelet Disord. 2024 Feb 16;25(1):146. doi: 10.1186/s12891-024-07270-y. PMID 38365661
• Bardakov SN, Tsargush VA, Carlier PG, Nikitin SS, Kurbatov SA, Titova AA, Umakhanova ZR, Akhmedova PG, Magomedova RM, Zheleznyak IS, Emelyantsev AA, Berezhnaya EN, A Yakovlev I, Isaev AA, Deev RV. Magnetic resonance imaging pattern variability in dysferlinopathy. Acta Myol. 2021 Dec 31;40(4):158-171. doi: 10.36185/2532-1900-059. eCollection 2021 Dec. PMID 35047756

Идентификаторы

NCT: NCT04824040 · DYSF-Observation (RUS)

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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