Atherosclerotic Narrowing of the Superficial Femoral Artery Clinical Trial
Official title:
Randomised Controlled Trial of Adjuvant Photodynamic Therapy to Reduce Restenosis After Percutaneous Transluminal Angioplasty to the Superficial Femoral Angioplasty
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.
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.
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Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Single Blind, Primary Purpose: Treatment