Ultrastructural Collagen Markers in Ehlers Danlos Syndromes

Decrypting the Ultrastructural Collagen Markers Using Quantitative Nano Histology: A Quest for Newer Diagnostic Test in Hypermobile Ehlers-Danlos Syndrome

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.

Study Overview

• Status: Enrolling by invitation
• Conditions: Ehlers-Danlos Syndrome; Hypermobile EDS (hEDS); Classical Ehlers-Danlos Syndrome
• Intervention / Treatment: Other: Skin Biopsy

• Study Type: Observational
• Enrollment (Estimated): 20

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada, M5G 2C4
      • GoodHope EDS - Toronto General Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Individuals with classical EDS and hypermobile EDS

Description

Inclusion Criteria:

• 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.

Exclusion Criteria:

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

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Control
• Time Perspectives: Cross-Sectional

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Individuals with hypermobile EDS; Skin biopsy collection	Other: Skin Biopsy; 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; Skin biopsy collection	Other: Skin Biopsy; 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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

Collaborators and Investigators

• Sponsor: University Health Network, Toronto

Study record dates

Study Major Dates

• Study Start (Actual): October 31, 2022
• Primary Completion (Estimated): June 1, 2024
• Study Completion (Estimated): August 1, 2024

Study Registration Dates

• First Submitted: June 17, 2022
• First Submitted That Met QC Criteria: June 17, 2022
• First Posted (Actual): June 24, 2022

Study Record Updates

• Last Update Posted (Actual): November 28, 2023
• Last Update Submitted That Met QC Criteria: November 27, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Cardiovascular Diseases; Vascular Diseases; Skin Diseases; Disease; Congenital Abnormalities; Hematologic Diseases; Hemorrhagic Disorders; Genetic Diseases, Inborn; Connective Tissue Diseases; Hemostatic Disorders; Skin Diseases, Genetic; Skin Abnormalities; Collagen Diseases; Syndrome; Ehlers-Danlos Syndrome
• Other Study ID Numbers: 21-5542.0

Drug and device information, study documents

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