Innovative Vascular Therapies for Patients with End-stage Renal Disease and Peripheral Arterial Disease

Advances in Cell Therapy to Improve Dialysis Access Outcomes
Grafts and fistulas placed in hemodialysis patients frequently fail, requiring numerous procedures and adversely affecting quality-of-life for these patients. New cell therapies are being developed to reduce the narrowing of vessels caused by scarring and abnormal tissue growth. Dr. Conte is the Co-lead Investigator of an FDA-approved, multicenter Phase I/II study assessing the efficacy and feasibility of Vascugel™, a new allogeneic cell therapy that strives to restore natural repair and regeneration pathways in the vasculature.

Sponsored by Pervasis Therapeutics, the V-HEALTH trial (Vascular Intimal Hyperplasia: Extending Arterial and Venous Patency, Limiting Vascular Trauma, and Inhibiting Hyperplasia While Re-establishing Vascular Health) is suitable for patients with end-stage renal disease (ESRD) who require permanent arteriovenous (AV) access – including AV grafts and AV fistulas – for hemodialysis. The study may also have broader implications for patients with peripheral arterial disease.

Biologic Therapies to Improve Clinical Outcomes of Vascular Interventions
Results of past studies of biologic interventions employing cells, genes, or other biological products in cardiovascular disease have been mixed but provide valuable insight for researchers and physicians. Vascular surgeons at Brigham and Women’s Hospital have pioneered efforts to improve the results of bypass surgery for patients with severe vascular disease. Dr. Conte served as lead investigator of a large, multicenter, randomized Phase III trial, The Project or Ex-Vivo vein graft Engineering via Transfection III (PREVENT III), assessing the effectiveness of the molecular therapy edifoligide in preventing vein graft failure in patients with critical limb ischemia (CLI).

While the recently published study concluded that this treatment did not reduce the incidence of vein graft stenosis in a large cohort of patients, the study demonstrated the safety and feasibility of delivering genetic material to vein grafts in the operating room setting, with the goal of re-engineering bypasses that are resistant to failure. Further investigations of this approach are warranted. In addition, the large clinical database resulting from PREVENT III has also allowed the investigators to make important new discoveries regarding risk factors for adverse outcomes following leg bypass surgery.

Other Advances
Experts in cardiovascular medicine and vascular surgery at Brigham and Women’s Hospital are collaborating in key research studies of factors contributing to peripheral arterial disease and vein graft disease. Mark A. Creager, MD, Director of the Vascular Center, Paul M. Ridker, MD, Director of the Center for Cardiovascular Disease Prevention, and Dr. Conte are leading a team of researchers in NIH-sponsored studies of:

• The role of inflammation and insulin resistance in the development and progression of peripheral arterial disease;
• The relationship of inflammation and insulin resistance to vein graft disease.

Multidisciplinary Approach to Care
The Cardiovascular Center offers a multidisciplinary approach to vascular care and full range of treatment options for patients with carotid artery disease, aortic aneurysms, peripheral arterial disease, and hemodialysis access needs. Vascular surgeons offer a full range of procedures, including minimally invasive endovascular repair, angioplasty/stenting, carotid endarterectomy, and surgical bypass procedures to restore circulation and prevent limb loss.

These specialists are working to develop improved approaches to identify and treat patients at risk, improve their walking function, and prevent the progression of disease in the native arteries or bypass grafts by targeting inflammatory processes. Patients are currently being recruited for several different arms of this prospective study.

Other actively enrolling clinical trials within the Division of Vascular and Endovascular Surgery include trials of carotid artery stenting, endovascular aneurysm repair, and angioplasty/ stenting of lower extremity vessels.

Indications for Referral
Patients with the following conditions may be referred for evaluation and treatment:

• Patients with ESRD requiring vein fistulas or grafts for hemodialysis access;
• Patients with lower extremity pain due to peripheral arterial disease;
• Patients with diabetic foot conditions and impaired circulation;
• Patients with aneursymal disease of the thoracic or abdominal aorta;
• Patients with carotid artery occlusive disease.

Information and Referrals
For more information regarding vascular surgery techniques at Brigham and Women’s Hospital, or to refer a patient, please contact a Referral Coordinator at (617) 732-9894.