STUDY PARAMETERS 
IV.A. Pre-treatment Studies (See Table 1) 
1) Medical history. 
2) Physical examination. 
3) Indices, pressures, and PVRs. 
4) Magnetic resonance angiography (MR A). To allow non-invasive monitoring of distal limb 
perfusion, MRA of the treated limb will be performed using gadolinium as previously described 64 
5) Duplex color/flow Doppler . To obtain flow velocity measurements at pre-determined 
anatomic sites (depending on the individual patient anatomy at baseline), duplex color/flow Doppler 
examination will be performed of the treated limb as previously described 
6) Transcutaneous oxygen pressure (TcO?). T cO? will be measured under resting conditions 
( 30 -minute adaptation time) at two different sites on the dorsal surface of the foot as previously described 
20, including in the region of ischemic ulcers if these are present. 
7) Spiral-computed tomography (sniral-CT), T o obtain high resolution definition of distal 
vasculature in the treated limb, spiral-CT will be performed using approximately 60cc of Renografin-43 
administered via a peripheral vein. 
8) Diagnostic angiography. To obtain definition of distal vasculature in treated limb using 
what is still regarded as "gold standard," diagnostic angiography will be performed using selective 
techniques from a contrateral retrograde or ipsilateal antegrade approach using < 50 cc of 50% dilute non- 
ionic contrast Cut film as well as digital images will be recorded. 
9) Quality of life (OOL). QOL will be measured by Health Status Survey questionnaire (HSS- 
SF-36) which the patient will be asked to complete alone. 
IV. B. Treatment 
Gene transfer itself will be performed percutaneously in an identical fashion to that used for the pre- 
clinical animal studies. If the profunda is the intended site of gene transfer, then a retrograde, wire-guided 
approach from the contralateral common femoral artery will be used, according to standard techniques, to 
advance the angioplasty catheter/sheath to the site of gene transfer under flouroscopic guidance. Once 
positioned, the sheath will be withdrawn, the balloon inflated for 5 minutes at nominal inflation pressures, 
following which the balloon will be deflated, drawn back into the sheath and removed. An angiogram will 
then be recorded to document the anatomy and collateral circulation at the time of gene transfer, and to 
confirm that no vessel trauma has occurred. 
If the distal superficial femoral artery or popliteal arteries represent the site of gene transfer, the 
approach will be antegrade and ipsilateral, but otherwise identical. 
IV.C. Post-Treatment Studies (See Table 1) 
1) Medical history. To be done weekly for three months; bi-weekly for three months; 
monthly thereafter for at least 24 months. 
2) Physical examination. To be done according to same schedule as medical history. 
3) Indices, pressures, and PVRs. To be done according to same schedule as medical history. 
4) Magnetic resonance angiography (MRA). To be done weekly X4, bi-weekly X4, monthly 
X4 and then q3 months up to 24 months. 
5) Duplex color/flow Doppler . To be done according to same schedule as MRA. 
6) Transcutaneous oxygen pressure (TcO?). To be done bi-weekly X2, monthly X4, and q6 
months up to 24 months. 
7) Spiral-computed tomography (spiral-CT). To be done bi-weekly X2, monthly X4, and q6 
months up to 24 months. 
8) Diagnostic angiography. To be done monthly X2, bi-monthly X2, and then q6 months up 
to 24 months. Moreover, if at any time less-invasive testing suggests a profound response to VEGF gene 
therapy, ad hoc diagnostic examination may be performed; it will be attempted, however, to limit 
angiographic examinations to no more than 2 per month. 
9) Quality of life (OOL). To be done according to same schedule as medical history. 
IV. D. Criteria for Response 
As indicated above, patients with PAD who will be considered for the current study will be 
limited to patients with rest pain and/or ischemic ulcers; accordingly, the primary clinical 
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