Biomarker for Duchenne Muscular Dystrophy

Completed

• Conditions: Red-Green Color Blindness; Lordosis; Muscular Atrophy; Increased Lordosis/Scoliosis; Hyporeflexia; Duchenne Muscular Dystrophy; Scoliosis; Muscular Weakness

• Registration Number: NCT02994030
• Lead Sponsor: CENTOGENE GmbH Rostock

Brief Summary

International, multicenter, observational, longitudinal study to identify biomarker/s for Duchenne Muscular Dystropy (DMD) and to explore the clinical robustness, specificity, and long-term variability of these biomarker/s.

Detailed Description

Duchenne Muscular Dystrophy (DMD) is a devastating inherited neuromuscular disorder that affects 1 in 3300 live male births (females can be mildly affected carriers). DMD causes progressive weakness and loss of muscle mass, with symptoms usually appearing in early childhood. DMD arises from mutations in the DMD gene that codes for dystrophin.

The DMD gene is located on the short arm of chromosome X (locus Xp21) and codes for dystrophin, containing 3685 amino acid residues. 60-65% of DMD mutations are large dele-tions, 10-30% are nonsense and frame-shift mutations, 5-15% are duplications, and 2% are intronic or 5'- and 3'-UTR alterations.Dystrophin aggregates as a homotetramer in the skeletal muscles or associates with actin and Dystrophin-Associated Glycoproteins (DAGs), forming a stable complex that interacts with laminin in the extracellular matrix. Dystrophin is considered a key structural element in the muscle fiber, whose primary function is to stabilize plasma mem-brane, while the DAGs maintain the sarcolemmal stability by mediating the complex interactions of the muscle membrane and extracellular environment. The low levels of dystrophin lead to cellular instability and progressive leakage of intracellular components, explaining the characteristically high levels of creatine phosphokinase (CPK) in the blood of DMD patients.

Biomarkers serve as measurable indicators of normal biological or pathological processes. They are typically directly linked to genetic variants in specific genes and can predict, diagnose, monitor, and assess the severity of a disease. It is the goal of this study to identify, validate, and monitor biochemical markers from DMD affected participants.

Study Timeline

• Study First Submitted: 2016-11-22
• Study First Submitted QC: 2016-12-13
• Study First Posted: 2016-12-15
• Study Start: 2018-08-20
• Status Verified: 2022-03
• Primary Completion: 2022-03-11
• Study Completion: 2022-03-11
• Last Update Submitted: 2022-03-23
• Last Update Posted: 2022-03-24

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 103

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Identification of DMD biomarker/s	36 weeks	All samples will be analyzed for the identification of biomarker/s via Liquid Chromatography Multiple Reaction-monitoring Mass Spectrometry (LC/MRM-MS) and compared to merged control, in order to establish the disease-specific biomarker/s. The LC/MRM-MS is performed on an ABSciex 6500 triple quadrupole mass spectrometer, coupled with a Waters Acquity UPLC.

Secondary Outcome Measures

Name	Time	Method
Exploring the clinical robustness, specificity, and long-term variability of DMD biomarker/s	36 months	Samples will be analyzed for the identified biomarker candidates via Liquid Chromatography Multiple Reaction-monitoring Mass Spectrometry (LC/MRM-MS) and compared to merged control, in order to establish the disease-specific biomarker/s. The LC/MRM-MS is performed on an ABSciex 6500 triple quadrupole mass spectrometer, coupled with a Waters Acquity UPLC.

Trial Locations

Locations (12)

University Hospital Center Mother Teresa; 🇦🇱 Tirana, Albania

American of science and technology; 🇱🇧 Beirut, Lebanon

Department of Pediatric,Faculty of Medicine, Alexandria University Children's Hospital; 🇪🇬 Alexandria, Egypt

Lady Ridgeway Hospital for Children; 🇱🇰 Colombo 8, Sri Lanka

Ain Shams University-Medical Genetics; 🇪🇬 Cairo, Egypt

Amrita Institute of Medical Sciences & Research Centre; 🇮🇳 Cochin, Kerala, India

Ain Shams University; 🇪🇬 Cairo, Egypt

Departmnet of Pediatrics, Tanta University; 🇪🇬 Tanta, Egypt

Departmnet of Molecular and Medical Genetics, Tbilisi State Medical University; 🇬🇪 Tbilisi, Georgia

Ain Shams Univirsity; 🇪🇬 Cairo, Egypt

Department of Pediatric Gastroenterology and Hepatology, The Children's Hospital and Institute of Child Health; 🇵🇰 Lahore, Pakistan

Emergency Hospital for Children "Louis Turcanu"; 🇷🇴 Timişoara, Romania