Clinical and Biochemical Features for the Identification of Dominant Calpainopathies (DOM-CAL)

Retrospective Analysis of Clinical and Biochemical Features for the Identification of Dominant Inheritance of Calpainopathies

Mutations in the CAPN3 gene cause muscular dystrophies with dysfunction in calpain-3. Calpainopathies are usually inherited in an autosomal recessive manner but in some families they can occur in a dominant inheritance. The significance of heterozygous variants is difficult to interpret in the absence of family history. In this study, the investigators will review the clinical and laboratory information in a cohort of patients identified in the participating centers, with the aim of improving the diagnostic strategy of dominant calpainopathies.

Study Overview

• Status: Enrolling by invitation
• Conditions: Calpain-3 Deficiency Limb Girdle Muscular Dystrophy Type 2A
• Intervention / Treatment: Other: retrospective study

Detailed Description

The investigators will review clinical and biomarker information in a cohort of 50 patients with heterozygous variants in the CAPN3 gene. Patients are referred by participating centers who will provide anonymised information on the clinical phenotype and laboratory test results. Suitable subjects will be contacted to obtain informed consent. Pseudonymised anamnestic data will be collected from the patient's clinical history and medical records.The aim is to identify a set of multidisciplinary data sufficient to define a diagnostic algorithm for the dominant calpainopathies.

• Study Type: Observational
• Enrollment (Estimated): 50

Contacts and Locations

Study Locations

• Italy
  • Venice-Lido, Italy
    • IRCCS San Camillo
  • VE
    • Venice-Lido, VE, Italy, 30126
      • San Camillo Irccs

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Suitable subjects identified in the participating centers.

Description

Inclusion Criteria:

• Clinical LGMD phenotype, family history with dominant inheritance or sporadic cases, single variant in CAPN3, second variant excluded by MLPA (Multiplex Ligation Probe Amplification) or by analysis of mRNA extracted from muscle.

Exclusion Criteria:

• No variants in CAPN3, two variants in CAPN3

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Muscle strenght	Evaluation of muscle strength with MRC Scale (score 1-5 from weaker to stronger)	through study completion, an average of 1 year
Muscle biopsy	Evaluation of histology and calpain 3 expression (present, reduced, absent)	through study completion, an average of 1 year
Creatin Kinase	Amount of creatine kinase in blood in units (U) of enzyme activity per liter (L) of serum	through study completion, an average of 1 year
Clinical history	Data collection sheet from clinical records	through study completion, an average of 1 year

Collaborators and Investigators

• Sponsor: IRCCS San Camillo, Venezia, Italy
• Collaborators: Universita di Verona; Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico; Istituto Giannina Gaslini; Azienda Ospedaliera Universitaria Senese; IRCCS Fondazione Stella Maris; Ospedale Policlinico San Martino
• Investigators: Principal Investigator: RITA BARRESI, DR, IRCCS San Camillo

Study record dates

Study Major Dates

• Study Start (Estimated): September 1, 2023
• Primary Completion (Estimated): September 1, 2024
• Study Completion (Estimated): June 5, 2025

Study Registration Dates

• First Submitted: June 30, 2023
• First Submitted That Met QC Criteria: July 19, 2023
• First Posted (Actual): July 21, 2023

Study Record Updates

• Last Update Posted (Actual): July 21, 2023
• Last Update Submitted That Met QC Criteria: July 19, 2023
• Last Verified: July 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Nervous System Diseases; Genetic Diseases, Inborn; Musculoskeletal Diseases; Muscular Diseases; Neuromuscular Diseases; Muscular Disorders, Atrophic; Muscular Dystrophies; Muscular Dystrophies, Limb-Girdle
• Other Study ID Numbers: 2023.08

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Data and images may be disclosed in strictly anonymous form through meetings, conferences and scientific publications. In any case, the name or any other detail suitable for identifying the individual participant will not be disclosed as the data may only be presented in aggregate form.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No