IGF-I Stimulation of Collagen Synthesis in Ehlers-Danlos Patients

Not Applicable

Completed

• Conditions: Ehlers-Danlos Syndrome, Classic
• Interventions: Drug: mecasermin; Drug: Saline

• Registration Number: NCT01446783
• Lead Sponsor: Bispebjerg Hospital

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.

Study Timeline

• Study Start: 2011-09
• Study First Submitted: 2011-09-27
• Study First Submitted QC: 2011-10-03
• Study First Posted: 2011-10-05
• Status Verified: 2012-11
• Primary Completion: 2012-11
• Study Completion: 2012-11
• Last Update Submitted: 2012-11-19
• Last Update Posted: 2012-11-20

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 15

Inclusion Criteria

• Classic form of Ehlers-Danlos syndrome OR healthy matched control

Exclusion Criteria

• Malignity, cardiac diseases, diabetes, tendinopathy in patella tendons

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: FACTORIAL

Arm && Interventions

Group	Intervention	Description
mecasermin + Ehlers-Danlos	mecasermin	-
Saline + Ehlers-Danlos	Saline	-
Mecasamin + healthy control	mecasermin	-
Saline + healthy control	Saline	-

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
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.

Trial Locations

Locations (1)

Institute of Sportsmedicine Copenhagen; 🇩🇰 Copenhagen, Denmark