An Investigation into the role of Matrix Metalloproteinases (MMPs) in Lower Limb Vascular Restenosis

• Register: ISRCTN
• Last refreshed on: 13 January 2015
• Main ID: ISRCTN35955220
• Date of registration: 29/09/2006
• Prospective Registration: No
• Primary sponsor: Record Provided by the NHSTCT Register - 2006 Update - Department of Health
• Public title: An Investigation into the role of Matrix Metalloproteinases (MMPs) in Lower Limb Vascular Restenosis
• Date of first enrolment: 18/07/2005
• Target sample size: 270
• Recruitment status: Completed
• URL: http://isrctn.com/ISRCTN35955220
• Study type: Interventional
• Study design: Randomised controlled trial (Treatment)

Countries of recruitment

United Kingdom

Contacts

• Name: Kevin Varty

Key inclusion & exclusion criteria

Inclusion criteria: Serum samples collected at the time of vascular intervention (radiologist or surgeon). Follow up samples by vascular research fellow.

Arterial wall and vein biopsies taken at the time of surgery by operating surgeon.
Exclusion criteria: 1. Patient unable to give informed consent
2. Age < 18 years
3. Pregnancy, planned pregnancy
4. Life expectancy less than 12 months
5. Inability to monitor the angioplasty site or graft with ultrasound for stenosis
6. Unable to take SDD (ie allergic reaction) or currently taking tetracyclines
7. Unable to take adjuvant treatment with antiplatelet/anticoagulant agent and statin

Age minimum:
Age maximum:
Gender: Not Specified

Health Condition(s) or Problem(s) studied

Surgery: Cardiovascular
Surgery
Cardiovascular

Intervention(s)

Patients under the care of the Cambridge Vascular Unit undergoing femoro-popliteal angioplasty or femoro-popliteal/tibial bypass will be eligible for the study. The indication for intervention will be severe limb ischaemia (rest pain, ulceration, gangrene) or short distance claudication failing to respond to medical and exercise therapy.

Pre-procedural Noninvasive Assessments:
Following informed consent the degree of ischaemia will be measured using ankle brachial pressure index (ABPI) measurements and transcutaneous oxygen measurements (TcPO2). Arterial stiffness and Endothelial Function will also be determined by applying a pressure probe to the carotid and radial arteries in turn with concomitant ECG gating.

Percutaneous Angioplasty:
These procedures are routinely carried out as either day cases or with overnight stay. During the procedure two 40 ml blood samples will be taken for plasma MMP analysis, plus CRP level, cholesterol, U&Es, elastin breakdown products, elastase activity and genetic analyses. One 40 ml sample will be systemic venous blood taken from the venous access cannula inserted for the procedure. A second 40 ml sample will be taken from the femoral vein in the leg undergoing the procedure. This is blood returning from the treated leg, and is more likely to reflect the local MMP activity potentially related to restenosis. On the same day as the PTA procedure the patients will be commenced on the SDD/placebo medication in a double blind randomised design. One tablet (25 mgs SDD) twice per day. This will be continued for 24 weeks post procedure.

Post Procedure Follow Up:
Colour duplex ultrasound assessment of the angioplasty site will be used to document blood velocities across the lesion and percentage of restenosis. These measurement will take place in the Vascular Laboratory at the following intervals: 1, 6, 12, 24, 36, 52 weeks. At 24 and 52 weeks repeat blood samples will be taken.

Femoro-distal bypass:
The same pre-procedural assessments

Primary Outcome(s)

1. MMP activities SDD versus placebo
2. CRP levels
3. Endothelial function and re-stenosis
4. Arterial wall stiffness and re-stenosis.

Secondary Outcome(s)

Not provided at time of registration

Secondary ID(s)

N0544170118

Source(s) of Monetary Support

Cambridge Consortium - Addenbrooke's (UK), NHS R&D Support Funding