Ehlers-Danlos Syndrome, Classic
Conditions
Keywords
COL5A1, Collagen disorders, IGF-I, Collagen synthesis
Brief summary
The investigators want to inject insulin-like growth factor-I (IGF-I) into the patella tendon of Ehlers-Danlos patients and healthy controls to evaluate the response in collagen synthesis. Furthermore collagen synthesis is measured in muscle connective tissue and in skin. The hypothesis is that the connective tissue in Ehlers-Danlos patients is more compliant and poorer in collagen than healthy controls, but that collagen synthesis can be stimulated by IGF-I.
Detailed description
IGF-I will be injected with ultrasound guidance to one patella tendon and the other one will be injected with saline as control. Injections will be performed double blinded and timed 24 hours and 6 hours before tissue sampling. Collagen synthesis will be measured as fractional synthesis rate based on stabile isotope technique using labelled proline. 10 patients diagnosed with Classical form of Ehlers-Danlos syndrome will be included and matched with 10 healthy controls based on age, gender, BMI and activity level. The muscle biopsy will be taken from vastus lateralis muscle and the skin biopsy from the buttocks. The biopsies will if the size permits it also be used for histology and mRNA analyses.
Interventions
DRUGmecasermin
0,1 ml mecasermin (10 mg/ml) is injected intratendinous into the patella tendon with ultrasound guidance.
DRUGSaline
0,1 ml saline is injected intratendinous into the patella tendon with ultrasound guidance.
Sponsors
Bispebjerg Hospital
Study design
Allocation
RANDOMIZED
Intervention model
FACTORIAL
Primary purpose
BASIC_SCIENCE
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
* Classic form of Ehlers-Danlos syndrome OR healthy matched control
Exclusion criteria
* Malignity, cardiac diseases, diabetes, tendinopathy in patella tendons
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Fractional synthesis rate of collagen in tendon, muscle and skin | 6 hours | A flood primed infusion of proline labelled with a stable isotope is used to calculate fractional synthesis rate of collagen in the 3 types of tissues. The infusion continues for 6 hours and tissue sampling is performed afterwards. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Electron microscopy | — | If there is additional tissue in the biopsies a piece will be stored for electron microscopy. In skin and tendon a transverse slice will be evaluated on collagen fibril diameter, form and density. In muscle the amount and appearance of connective tissue will be studied. |
| mRNA | — | From the muscle biopsy a piece will be stored for mRNA analysis if possible. Targets will be collagen types and IGF-I isoforms. |
Countries
Denmark
Outcome results
None listed