Origins and Impact of EDS in Connective Tissues and Skin

Study Overview
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Brief Summary
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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.

Official Title
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Origins and Impact of EDS in Connective Tissues and Skin

Conditions
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Ehlers-Danlos Syndrome

Intervention / Treatment
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* Procedure: Orthopaedic & Gynaecology surgery


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Skin<br>Patients with EDS diagnosis having surgery, have debrided skin retained for this research | Procedure: Orthopaedic & Gynaecology surgery<br>* 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.<br>|
| Tendon<br>Patients with EDS diagnosis having surgery, have debrided tendon retained for this research | Procedure: Orthopaedic & Gynaecology surgery<br>* 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.<br>|
| Uterine tissue<br>Patients with EDS diagnosis having surgery, have debrided uterine tissue retained for this research | Procedure: Orthopaedic & Gynaecology surgery<br>* 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.<br>|
| Vaginal tissue<br>Patients with EDS diagnosis having surgery, have debrided vaginal tissues retained for this research | Procedure: Orthopaedic & Gynaecology surgery<br>* 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.<br>|
| Ligaments<br>Patients with EDS diagnosis having surgery, have debrided ligaments retained for this research | Procedure: Orthopaedic & Gynaecology surgery<br>* 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.<br>|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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hypermobility, collagen, joint, hyperflexation