Back to resultsIGF-I Stimulation of Collagen Synthesis in Ehlers-Danlos Patients
Primary Purpose
Ehlers-Danlos Syndrome, Classic
Status
Completed
Phase
Not Applicable
Locations
Denmark
Study Type
Interventional
Intervention
mecasermin
Saline
Sponsored by
About this trial
This is an interventional basic science trial for Ehlers-Danlos Syndrome, Classic focused on measuring COL5A1, Collagen disorders, IGF-I, Collagen synthesis
Eligibility Criteria
Inclusion Criteria:
- Classic form of Ehlers-Danlos syndrome OR healthy matched control
Exclusion Criteria:
- Malignity, cardiac diseases, diabetes, tendinopathy in patella tendons
Sites / Locations
- Institute of Sportsmedicine Copenhagen
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm Type
Active Comparator
Placebo Comparator
Active Comparator
Placebo Comparator
Arm Label
mecasermin + Ehlers-Danlos
Saline + Ehlers-Danlos
Mecasamin + healthy control
Saline + healthy control
Arm Description
Outcomes
Primary Outcome Measures
Fractional synthesis rate of collagen in tendon, muscle and skin
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
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.
Full Information
NCT ID
NCT01446783
First Posted
September 27, 2011
Last Updated
November 19, 2012
Sponsor
Bispebjerg Hospital
1. Study Identification
Unique Protocol Identification Number
NCT01446783
Brief Title
IGF-I Stimulation of Collagen Synthesis in Ehlers-Danlos Patients
Official Title
IGF-I Stimulation of Collagen Synthesis in Ehlers-Danlos Patients
Study Type
Interventional
2. Study Status
Record Verification Date
November 2012
Overall Recruitment Status
Completed
Study Start Date
September 2011 (undefined)
Primary Completion Date
November 2012 (Actual)
Study Completion Date
November 2012 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Bispebjerg Hospital
4. Oversight
Data Monitoring Committee
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Ehlers-Danlos Syndrome, Classic
Keywords
COL5A1, Collagen disorders, IGF-I, Collagen synthesis
7. Study Design
Primary Purpose
Basic Science
Study Phase
Not Applicable
Interventional Study Model
Factorial Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
15 (Actual)
8. Arms, Groups, and Interventions
Arm Title
mecasermin + Ehlers-Danlos
Arm Type
Active Comparator
Arm Title
Saline + Ehlers-Danlos
Arm Type
Placebo Comparator
Arm Title
Mecasamin + healthy control
Arm Type
Active Comparator
Arm Title
Saline + healthy control
Arm Type
Placebo Comparator
Intervention Type
Drug
Intervention Name(s)
mecasermin
Other Intervention Name(s)
Increlex (mecasermin), Ipsen
Intervention Description
0,1 ml mecasermin (10 mg/ml) is injected intratendinous into the patella tendon with ultrasound guidance.
Intervention Type
Drug
Intervention Name(s)
Saline
Intervention Description
0,1 ml saline is injected intratendinous into the patella tendon with ultrasound guidance.
Primary Outcome Measure Information:
Title
Fractional synthesis rate of collagen in tendon, muscle and skin
Description
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.
Time Frame
6 hours
Secondary Outcome Measure Information:
Title
Electron microscopy
Description
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.
Title
mRNA
Description
From the muscle biopsy a piece will be stored for mRNA analysis if possible. Targets will be collagen types and IGF-I isoforms.
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria:
Classic form of Ehlers-Danlos syndrome OR healthy matched control
Exclusion Criteria:
Malignity, cardiac diseases, diabetes, tendinopathy in patella tendons
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Michael Kjaer, Professor
Organizational Affiliation
Institute of Sportsmedicine Copenhagen
Official's Role
Study Director
Facility Information:
Facility Name
Institute of Sportsmedicine Copenhagen
City
Copenhagen
ZIP/Postal Code
2400
Country
Denmark
12. IPD Sharing Statement
Learn more about this trial
IGF-I Stimulation of Collagen Synthesis in Ehlers-Danlos Patients
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