Origins and Impact of EDS in Connective Tissues and Skin

Ehlers-Danlos Syndrome (EDS) is an inherited disease of collagen, found in connective tissues, such as skin. EDS patients suffer from joint and skin problems (skin hyperextensibility, joint hypermobility) along with a large range of other disorders, including, delayed wound healing with atrophic scarring, easy bruising, tissue fragility, gastrointestinal and gum problems. There are many different types of EDS, with different mechanisms of action, and not all of these are well understood. This study will used advanced microscopy techniques called atomic force microscopy (AFM) and scanning electron microscopy (SEM) to analyse the changes in collagen as a result of EDS, compared to normal collagen. These changes will be viewed at the micron and nanoscale level (between 1,000 to 100,000 x magnification), and will focus on the differences in collagen construction through a process called cross-linking. These changes could potentially help clinicians understand the root cause of EDS symptoms, and provide a deeper knowledge of cross-linking disorders in collagen. Increasing our knowledge of how collagen is affected in EDS patients, may lead to improved treatment options for patients.

Study Overview

• Status: Unknown
• Conditions: Ehlers-Danlos Syndrome
• Intervention / Treatment: Procedure: Orthopaedic & Gynaecology surgery

• Study Type: Observational
• Enrollment (Anticipated): 35

Contacts and Locations

Study Locations

• United Kingdom
  • London, United Kingdom, NW1 2BU
    • University Collage Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Eligible patients will be identified from screening of all new and existing Hypermobility, Orthopaedics and Gynaecology clinics at UCLH and invited to participate in the study. The appropriate information sheet will be given to the patients who have been identified for elective surgery as part of their treatment plan and meeting the inclusion.

Description

Inclusion Criteria:

• Adult (18+) patients requiring elective surgery as part of their treatment plan who fulfil the Brighton criteria for Joint Hypermobility Syndrome (JHS)/EDS hypermobility type with significant joint hypermobility (Beighton score of 6 and above) and /or have evidence of significant connective tissue weakness, or rectal/vaginal prolapse

Exclusion Criteria:

• Patients with insufficient ability in English to give informed consent, if a translator is not present.
• Patients with severe developmental disorders, precluding their consent for research

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Control
• Time Perspectives: Prospective

Number of groups / cohorts

5

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Skin; Patients with EDS diagnosis having surgery, have debrided skin retained for this research	Procedure: Orthopaedic & Gynaecology surgery; Patients will have the surgery they require for their treatment. During surgery, debrided tissues will be retained for research. No treatment plans will be altered for this research.
Tendon; Patients with EDS diagnosis having surgery, have debrided tendon retained for this research	Procedure: Orthopaedic & Gynaecology surgery; Patients will have the surgery they require for their treatment. During surgery, debrided tissues will be retained for research. No treatment plans will be altered for this research.
Uterine tissue; Patients with EDS diagnosis having surgery, have debrided uterine tissue retained for this research	Procedure: Orthopaedic & Gynaecology surgery; Patients will have the surgery they require for their treatment. During surgery, debrided tissues will be retained for research. No treatment plans will be altered for this research.
Vaginal tissue; Patients with EDS diagnosis having surgery, have debrided vaginal tissues retained for this research	Procedure: Orthopaedic & Gynaecology surgery; Patients will have the surgery they require for their treatment. During surgery, debrided tissues will be retained for research. No treatment plans will be altered for this research.
Ligaments; Patients with EDS diagnosis having surgery, have debrided ligaments retained for this research	Procedure: Orthopaedic & Gynaecology surgery; Patients will have the surgery they require for their treatment. During surgery, debrided tissues will be retained for research. No treatment plans will be altered for this research.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Histological changes in EDS compared with healthy collagen using light microscopy after staining	Light microscopy will be qualitatively used to observe colour changes after staining between healthy and EDS collagen	1-5 years
Collagen morphological changes in EDS compared with healthy collagen using AFM and SEM	AFM and SEM will be used to qualitatively observe changes in orientation in collagen.	1-5 years
Collagen topographical changes in EDS compared with healthy collagen using AFM and SEM	AFM and SEM will be used to observe changes in length, width and height of healthy and EDS collagen, as well as D-band length. This will be measured in meters (nm).	1-5 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Collagen Young's modulus changes in EDS compared with healthy collagen using AFM	AFM will be used to calculate the Young's (elastic) modulus of the EDS and healthy collagen. This will be measured in Pascals (GPa).	1-5 years
Collagen nanoscale adhesion changes in EDS compared with healthy collagen using AFM	AFM will be used to calculate the changes in adhesion force of the EDS and healthy collagen. This will be measured in Newtons (nN). Quantitative outcomes: changes in Young's (elastic) modulus, changes in adhesion force, changes in single molecule pulling force	1-5 years
Collagen nanoscale single molecule pulling force in EDS compared with healthy collagen using AFM	AFM will be used to calculate the changes in pulling force of single molecules of EDS and healthy collagen. This will be measured in Newtons (nN).	1-5 years

Collaborators and Investigators

• Sponsor: University College, London
• Collaborators: University College London Hospitals
• Investigators: Principal Investigator: Hanna Kazkaz, UCLH; Principal Investigator: Laurent Bozec, UCL; Principal Investigator: Adam Strange, UCL; Principal Investigator: Rodney Graham, UCL; Principal Investigator: Susan Parekh, UCLH

Study record dates

Study Major Dates

• Study Start (Actual): April 1, 2017
• Primary Completion (Anticipated): December 1, 2020
• Study Completion (Anticipated): April 1, 2021

Study Registration Dates

• First Submitted: March 2, 2016
• First Submitted That Met QC Criteria: March 22, 2016
• First Posted (Estimate): March 29, 2016

Study Record Updates

• Last Update Posted (Actual): March 27, 2020
• Last Update Submitted That Met QC Criteria: March 25, 2020
• Last Verified: March 1, 2020

More Information

Terms related to this study

• Keywords: collagen; joint; hypermobility; hyperflexation
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Skin Diseases; Congenital Abnormalities; Hematologic Diseases; Hemorrhagic Disorders; Genetic Diseases, Inborn; Connective Tissue Diseases; Hemostatic Disorders; Skin Diseases, Genetic; Skin Abnormalities; Collagen Diseases; Ehlers-Danlos Syndrome
• Other Study ID Numbers: 15/0438

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No
• IPD Plan Description: No data will be shared outside of this research