Ultrastructural Collagen Markers in Ehlers Danlos Syndromes

Ehlers-Danlos Syndrome Clinical Trial

Official title:

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

Clinical Trial Details — Status: Enrolling by invitation

Administrative data

• NCT number: NCT05429996
• Other study ID #: 21-5542.0
• Status: Enrolling by invitation
• Start date: October 31, 2022
• Est. completion date: August 1, 2024

Study information

• Verified date: November 2023
• Source: University Health Network, Toronto
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

Recruitment information / eligibility

• Status: Enrolling by invitation
• Enrollment: 20
• Est. completion date: August 1, 2024
• Est. primary completion date: June 1, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Ehlers-Danlos Syndrome
• Hypermobile EDS (hEDS)
• Syndrome

Intervention

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

Locations

Country	Name	City	State
Canada	GoodHope EDS - Toronto General Hospital	Toronto	Ontario

Sponsors (1)

Lead Sponsor	Collaborator
University Health Network, Toronto

Country where clinical trial is conducted

Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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