Ultrastructural Collagen Markers in Ehlers Danlos Syndromes

NCT05429996 | Unknown

• 1 other identifier: 21-5542.0
• Study Type: observational
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

Establishing the diagnosis of Ehlers Danlos Syndromes (EDS)/generalized hypermobility spectrum disorders (G-HSD) is often problematic for patients. The absence of a precise unifying diagnosis in patients results in a significant emotional burden on the patient and caregivers, not to mention the hidden costs, including multiple recurring visits to several medical specialists and associated social and economic costs. To date, while collagen ultra-scale morphological heterogeneity has been used to comment on an EDS diagnosis, the mechanical properties of the collagen remain mostly unexplored. From a biophysical point of view, collagen affected with hEDS can be described as biomechanically deficient. In the case of EDS, the skin's abnormal elasticity can be directly related to the organization of the collagen network within the dermis. Quantitative Nanohistology (QNH) is a newer method to evaluate both the structural and mechanical properties of collagen in-situ histological sections. Therefore, the aim of this study is to define histo-biophysical markers of two most common types of EDS i.e. classical EDS (cEDS) \& hypermobile EDS (hEDS) at the single collagen fibrils level and matrix and to further explore the origin of collagen fibril properties deficiency in hEDS and cEDS.

Conditions

Ehlers-Danlos Syndrome; Classical Ehlers-Danlos Syndrome; Hypermobile EDS (hEDS)

Outcome Measures

Primary Outcomes (1)

• to analyze percentage prevalence of abnormal morphological markers of single collagen fibril using atomic force microscopy

  systemic nanoscale imaging to investigate the presence of morphological markers associated with each EDS type and compared to the normative data from the Bozec-lab obtained from healthy volunteers. These markers include fibrils D-banding periodicity, unwinding of the fibrils, variation in fibrils registration, and finally, cylindrical homogeneity (of the fibril

  3 months

Study Arms (2)

Individuals with hypermobile EDS

Skin biopsy collection

Other: Skin Biopsy

Individuals with classical EDS

Skin biopsy collection

Other: Skin Biopsy

Interventions

Skin Biopsy OTHER

Skin biopsy specimens will be collected for both groups and subjected to quantitative nano histology using atomic force microscopy to assess for structural profile of a single collagen fibril

Individuals with classical EDS; Individuals with hypermobile EDS

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

Individuals with classical EDS and hypermobile EDS

You may qualify if:

• Adults aged between 18 and 60 years who can provide informed consent in English
• Able to read, speak, and comprehend English without the assistance of a translator
• Have been diagnosed with hypermobile EDS as per the 2017 EDS criteria; or with genetically confirmed classical EDS (age and sex-matched). This diagnosis is carried out by the UHN GoodHope EDS clinic routinely for all patients on the basis of clinical exam and genetic testing, if indicated.

You may not qualify if:

• Subjects under the age of 18
• Unable to speak, read and comprehend English
• Unable to provide consent (cognitive impairment)
• Pregnant women

Sponsors & Collaborators

• University Health Network, Toronto: lead

Study Sites (1)

GoodHope EDS - Toronto General Hospital

Toronto, Ontario, M5G 2C4, Canada

Location

Biospecimen

Retention: SAMPLES WITH DNA

Skin biopsy samples of individual with cEDS and hEDS will be collected for the study

MeSH Terms

Conditions

Ehlers-Danlos Syndrome; Ehlers-Danlos syndrome type 1; Ehlers-Danlos syndrome type 3

Condition Hierarchy (Ancestors)

Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Hemorrhagic Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Skin Abnormalities; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Skin Diseases, Genetic; Genetic Diseases, Inborn; Collagen Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Skin Diseases

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: CROSS SECTIONAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Staff Physician/Clinical Investigator

Study Record Dates

• First Submitted: June 17, 2022
• First Posted: June 24, 2022
• Study Start: October 31, 2022
• Primary Completion: June 1, 2024
• Study Completion: August 1, 2024
• Last Updated: November 28, 2023

Record last verified: 2023-11

Locations

CA (1)