Follow-up Study on Female Carriers With DMD Gene Variants

NCT05715957 | Enrolling By Invitation DMC

• 1 other identifier: 98434
• Study Type: observational
• Target: 103
• Locations: 1 country
• Sites: 1

Brief Summary

Background Duchenne and Becker muscular dystrophies are X-linked recessive allelic disorders caused by mutations of the dystrophin gene on chromosome Xp21. Female carriers may pass on the pathogenic variant to their daughters, resulting in a significant number of female carriers of pathogenic DMD variants. There was a large variability in the severity of symptoms with some being asymptomatic and some having severe symptoms. Skewed X-Chromosome Inactivation (XCI) might explain some of this variability. But now, the underlying cause of the large variability in phenotype is therefore uncertain. Aim

1. 1.To describe the change over a 6-year follow-up period in the structure and function of the heart and in function and muscle fat fraction in skeletal muscle of DMD/BMD carriers.
2. 2.To explain the relationship between the XCI and the severity of the disease (phenotype).
3. 3.To compare cardiac affection of female carriers of DMD/BMD to patients with BMD using new cardiac MRI techniques (spectroscopy and Dixon sequences).

Conditions

Muscular Dystrophy; Duchenne Muscular Dystrophy; Becker Muscular Dystrophy

Keywords

XCI; follow up; MRI; spectroscopy

Outcome Measures

Primary Outcomes (5)

• Change in fat fraction

  Change in fat fraction (in %) in leg muscles from baseline to 6-year follow-up

  30 minutes

• Change in fibrosis in the heart

  Change in fibrosis (in %) in the heart from baseline to 6-year follow-up

  1 hour

• Change in LVEF/GLS-score

  Change in LVEF/GLS-score (in %) in the heart from baseline to 6-year follow-up

  1 hour

• Correlation between XCI and phenotype

  Correlation between XCI (ratio of healthy vs mutant X chromosome) and phenotype (from fat fraction and clinical symptoms). Correlation measured using linear regression.

  1 hour

• Cardiac status in patients with BMD vs carriers of variants in the DMD gene

  Correlation between cardiac structure and function (measured through Dixon and spectroscopy from cardiac MRI) between patients with BMD and carriers of genetic variants of the DMD gene.

  1 hour

Secondary Outcomes (10)

• Change in contractility

  1 hour

• Change in blood concentrations

  1 hour

• Change in blood concentrations

  1 hour

• Change in blood concentrations

  1 hour

• Change in blood concentrations

  1 hour

Study Arms (2)

female carriers of DMD gene variants

Other: No intervention

patients with BMD

Other: No intervention

Interventions

No intervention OTHER

No intervention

female carriers of DMD gene variants; patients with BMD

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

All patients are identified from the Department of Clinical Genetics and Copenhagen Neuromuscular Center, Rigshospitalet. We aim at including the 53 carriers of DMD variants that we investigated 6 years ago for Part 1. These patients will be asked to participate in Part 2 as well (optional). If we cannot recruit 20 patients for Part 2 from Part 1 (see Power Calculation), we will recruit new patients identified from the Department of Clinical Genetics or Copenhagen Neuromuscular Center, Rigshospitalet. We need 32 patients with BMD for Part 3 (see Power Calculation), which will be recruited from Copenhagen Neuromuscular Center, Rigshospitalet.

You may qualify if:

• Female gender
• Verified carrier of DMD gene mutations through genetic testing.
• Age of 18 years or more
• Participation in the study 6 years ago
• Contraindications to MRI (pacemaker or other internal metal or magnetic devices)
• Claustrophobia.
• Pregnant or nursing women.
• Competing disorders and other muscle disorders, which may alter measurements of i.e., muscle strength. The investigator will decide whether or not the competing disorder can significantly influence the results.
• Patients will be investigated with all other measurements than MRI if not eligible for MRI.
• Part 2:
• Female gender
• Verified carrier of DMD gene mutations through genetic testing.
• Age of 18 years or more

You may not qualify if:

• Anticoagulating medicine that cannot be paused due to health reasons
• Part 3:
• Genetically verified patient with BMD
• Age of 18 years or more
• Contraindications to MRI (pacemaker or other internal metal or magnetic devices)
• Claustrophobia.
• Atrial fibrillation
• Competing disorders and other muscle disorders, which may alter measurements of i.e., muscle strength. The investigator will decide whether or not the competing disorder can significantly influence the results.

Sponsors & Collaborators

• Rigshospitalet, Denmark: lead

Study Sites (1)

Copenhagen neuromuscular center

Copenhagen, 2100, Denmark

Location

Biospecimen

Retention: SAMPLES WITH DNA

Blood tests: Blood samples will be drawn and analyzed for cardiac markers (myoglobin, creatine kinase, creatine kinase MB, pro-brain natriuretic peptide (proBNP), and troponin T (TnT)) and proteomics. Biopsy procedure: Muscle biopsies will be sent to the Department of Clinical Genetics (Rigshospitalet) for genetic analysis to investigate the X-chromosome inactivation pattern. No other genetic information will be obtained during these tests.

MeSH Terms

Conditions

Muscular Dystrophies; Muscular Dystrophy, Duchenne

Condition Hierarchy (Ancestors)

Muscular Disorders, Atrophic; Muscular Diseases; Musculoskeletal Diseases; Neuromuscular Diseases; Nervous System Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Genetic Diseases, X-Linked

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD,PhD student

Study Record Dates

• First Submitted: January 27, 2023
• First Posted: February 8, 2023
• Study Start: May 18, 2023
• Primary Completion: August 1, 2025
• Study Completion: December 1, 2025
• Last Updated: June 6, 2025

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will not share

Locations

DK (1)