Clinical trial NCT00187811: The Safety and Efficacy of Photodynamic Therapy for Femoral Artery Stenosis
Official title: Randomised Controlled Trial of Adjuvant Photodynamic Therapy to Reduce Restenosis After Percutaneous Transluminal Angioplasty to the Superficial Femoral Angioplasty
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
PHASE3
Conditions: Atherosclerotic Narrowing of the Superficial Femoral Artery
Atherosclerotic Occlusion of the Superficial Femoral Artery
Keywords: Angioplasty,
Restenosis,
Photodynamic therapy
Lead sponsor: University College London Hospitals
Sponsor class: OTHER
Collaborators: name: UCL/UCLH Clinical Research and Development Fund
First posted: 2005-09-16
Enrollment: 120
Sex: ALL
Minimum age (years): 0
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: Rstenosis is common after angioplasty of atherosclerotic disease of the femoral artery. Pilot study data suggests that adjuvant photodynamic therapy, using delta amino kleavulinic acid as a photosensitiserr is feasible and safe. This study will examine safety in a larger population and,if recruitment numbers allow, efficacy will be assessed.

Hypothesis:

ALA photodynamic therapy is safe and well tolerated as an adjuvant to angioplasty as a treatment for femoral artery atherosclerotic stenosis or occlusion. A secondary endpoint will be sought : hypothesis : PDT will reduce in restenosis rates following adjuvant photodynamic therapy compared with standard balloon angioplasty in the treatment of superficial femoral arterial disease.

Detailed description: Background:

Percutaneous Transluminal Angioplasty (PTA) is well recognised as a treatment for obstructive vascular disease. Despite an initial high procedural success the technique is limited by the subsequent development of restenosis in up to 50% of patients between 3 and 6 months. ,

The pathological hallmark of restenosis has long been considered to be the development of neointimal hyperplasia consisting of smooth muscle cells and extracellular matrix. We now realise however that both elastic recoil of the vessel and the concept of remodelling are important in determining the overall response of the vessel to injury. Remodelling involves a geometric change in the vessel such that the maximum arterial dimension may increase (positive remodelling) or decrease (negative remodelling). , ,

Despite extensive research no pharmacological or interventional strategy has been shown to have an overwhelming effect on restenosis rates after angioplasty. Recently attention has been focused on the potential of intraluminal radiation therapy (Brachytherapy) and whilst this technique has shown considerable promise there are concerns regarding the long term complications and safety of the ionising radiation for non-malignant disease with reports of vessel wall damage after treatment. ,

Photodynamic therapy is a novel technique that involves the activation of a previously administered photosensitising agent by non thermal laser light. This results in the generation of reactive oxidative products with resulting tissue effects. It is a technique that has been used in the treatment of a variety of malignancies but the realisation that it may influence the response of the vessel wall after balloon injury has been particularly promising. 5 Aminolaevulinic acid (ALA) is a relatively new photosensitising agent which is converted to an active metabolite, Protoporphyrin IX (PPIX) in the biosynthesis of haem. In small animal models photodynamic therapy has been shown to cause medial smooth muscle cell depletion and to reduce the degree of neointimal hyperplasia after injury with no detrimental effects on the mechanical integrity of the vessel wall. , Large animal work using a swine model has confirmed these findings and has also demonstrated that favourable vessel wall remodelling occurs after PDT. Repopulation of the media with smooth muscle cells, after early depletion, has also been demonstrated which is likely to be important when we consider the long term effects of this treatment on the vessel wall.

The use of a large animal model enabled the development of an endovascular system for the delivery of laser light. As a result, and in the light of the findings from large animal studies, it has now been possible to conduct a pilot clinical study looking at the safety and efficacy of adjuvant PDT in patients undergoing repeat PTA for superficial femoral artery (SFA) disease who had restenosed less than 6 months after an earlier angioplasty. In this study it was shown that all patients were asymptomatic 6 months after the procedure with adjuvant PDT there were no arterial or procedural complications. These findings were supported by improvements in non-invasive endpoints and the abscence of significant restenosis as assessed by digital subtraction angiography.

These results were encouraging and we are now in a position to conduct a randomised clinical trial looking at standard balloon angioplasty with and without adjuvant photodynamic therapy in the treatment of peripheral vascular disease.

Eligibility criteria: Inclusion Criteria:

* Clinical diagnosis of claudication suggested by preliminary Duplex study to be due to superficial femoral artery stenosis or occlusion

Exclusion Criteria:

* Previous surgical graft to superficial femoral artery Known liver dysfunction Previous history of photosensitivity

Primary outcomes:
measure: Death
measure: Procedural complications (occlusion, haematoma)
measure: Arterial complications: aneursym, thrombus
measure: Surgical revascularisation (Emergency/Elective)
measure: Repeat PTA
measure: Limb loss
Secondary outcomes:
measure: Reccurence of claudication
measure: > 50% loss of initial lumen gain on duplex scanning
measure: PSVR > 2.0
measure: Fall in ABPI
measure: Measured Pre procedure, at 24h then at 1, 3 and 6 months.
measure: A final follow up is planned at 3-5 years
Other outcomes:
Locations:
city: London
country: United Kingdom
facility: University College London NHS Foundation Trust
Study officials:
affiliation: University College, London
name: Jean R McEwan, MB ChB FRCP
role: PRINCIPAL_INVESTIGATOR
affiliation: University College, London
name: Stephen Bown, PhD FRCP
role: STUDY_DIRECTOR
References: