EW-A-401 to Treat Intermittent Claudication

NCT00080392 | Completed Phase 1

• 2 other identifiers: 04014304-H-0143
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 3

Brief Summary

This study will test the safety of a drug called EW-A-401 in patients with intermittent claudication - pain and discomfort in the legs due to blockages of the arteries. The study will also evaluate whether EW-A-401 improves blood flow to the legs. EW-A-401 contains genetic material (DNA) that instructs the body to produce specific proteins that promote the growth of new blood vessels and may, therefore, improve blood flow to the legs. Patients 21 years of age and older with pain or discomfort of one or both legs due to blockages of the arteries below the groin may be eligible for this study. Candidates are screened with a medical history, physical examination, blood and urine tests, eye examination, chest x-ray and CT scan of the chest, and treadmill tests. Patients who are able to exercise more than 12 minutes on the treadmill may not enroll in the study. Participants undergo the following procedures:

• Muscle biopsy: On the first day of the study, patients have a muscle biopsy. This procedure is done under local anesthesia with mild sedation. A 1-inch incision is cut into the skin over a calf muscle and a small amount of muscle tissue is removed for examination by a pathologist.
• Drug treatment and tests: About 10 to 13 days after the biopsy, patients are admitted to the NIH Clinical Center for 3 to 5 days for drug treatment and tests. They receive 10 injections of either the study drug (EW-A-401) or placebo (an inactive substance) in each leg during a single session lasting about 1 hour. In addition, they have blood and urine tests, complete questionnaires about their symptoms, and undergo magnetic resonance imaging (MRI), a test that a magnetic field and radio waves to produce detailed images of body tissues and organs. For this procedure, the patient lies on a table that slides into the scanner (a large hollow tube) for imaging of the blood vessels in the legs. Patients wear headphones to muffle loud knocking and thumping sounds that occur during the scanning process.
• 30-day follow-up: Patients return to the Clinical Center three times over 30 days following the hospital stay for a medical history, physical examination, and blood and urine tests to assess the safety of EW-A-401.
• Extended follow-up: Patients return to the Clinical Center at 3, 6, and 12 months after hospitalization for a medical history and physical examination, blood and urine tests, two treadmill tests, questionnaires about symptoms, and MRI studies, including imaging for blood flow measurement. Blood flow to the legs is measured during MRI using large blood pressure cuffs inflated around the legs during the scanning. The cuffs are inflated very tightly for 5 minutes, and then a dye is injected into an arm vein to brighten the images. Additional pictures are taken over the next 5 to 10 minutes. At two of these follow-up visits, patients also have an eye examination, and at the 3- or 6-month visit they have a repeat muscle biopsy of the calf. The study lasts 12 months. After 6 months, patients will be told whether they received EW-A-401 or placebo. Because EW-A-401 is so new, patients will continue to be contacted every year after the study is completed.

Conditions

Intermittent Claudication; Arteriosclerosis

Keywords

Gene Transfer; Therapeutic Angiogenesis; Peripheral Arterial Disease; Perfusion; Magnetic Resonance Imaging; Peripheral Vascular Disease; Claudication; PAD; Leg Claudication; Intermittent Claudication

Interventions

DNA Plasmid Vector DRUG

EW-A-401 DNA Plasmid Vector DRUG

Eligibility Criteria

• Age: 21 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Adults greater than or equal to 21 years.
• Limiting lower limb intermittent claudication due to infra-inguinal obstructive atherosclerosis, not optimal for catheter-based treatment.
• Patient femoral artery inflow by radio contrast or magnetic resonance angiography within the previous 12 months.
• Stable symptoms for at least 4 months.
• Peak walking time (PWT) on standardized Gardner Exercise Treadmill Exam between 1 and 12 minutes.
• Resting ankle-brachial systolic blood pressure index (ABI) less than 0.9 in the more-affected limb.
• Bilateral PAD for subjects enrolled into Strata C-F with the less-affected limb having any of the following:
• Resting or post-exercise ABI less than or equal to 0.9.
• Typical intermittent claudication.
• Infrainguinal obstructive atherosclerosis in a femoropopliteal and/or tibial artery greater than or equal to 70%.
• Subjects enrolled into Strata A and B may have both unilateral or bilateral peripheral atherosclerotic disease.

You may not qualify if:

• Any history of malignancy or a known genetic predisposition for developing cancer except for curatively resected basal cell carcinoma of skin, squamous cell carcinoma of skin, cervical carcinoma in situ, or resected benign colonic polyps.
• Non-compressible arteries (resting ankle-brachial systolic blood pressure index (ABI) greater than 1.3 in the more-affected limb).
• Evidence of malignancy after screening according to modified American Cancer Society Guidelines in the following organ systems (screening procedures in addition to history and physical exam are noted):
• Prostate: subjects with the following PSA levels above the recommended age-specific cut-points will be excluded
• Age 50-59 greater than or equal to 3.7
• Age 60-69 greater than or equal to 5.1
• Age 70-79 greater than or equal to 7.0
• Age 80 plus-greater than or equal to 7.2
• Subjects with PSA values above the age-specific cut-points are eligible if a prostate biopsy, within 12 months, shows neither prostate cancer nor high-grade prostatic intraepithelial neoplasia (PIN).
• Breast: mammogram
• Cervix: Pap smear
• Colon: Colonoscopy
• Skin
• Lung: contrast chest CT scan
• Proliferative retinopathy, severe non-proliferative retinopathy, advanced age-related macular degeneration, especially subjects with chorodial neovascularization, diabetic retinopathy, macular edema, or intraocular surgery within 3 months.

Sponsors & Collaborators

• National Heart, Lung, and Blood Institute (NHLBI): lead

Study Sites (3)

Baptist Health System, Inc.

Birmingham, Alabama, 35213, United States

Location

National Institutes of Health Clinical Center, 9000 Rockville Pike

Bethesda, Maryland, 20892, United States

Location

University of Wisconsin

Madison, Wisconsin, 53792, United States

Location

Related Publications (3)

• Anderson WF. What about those monkeys that got T-cell lymphoma? Hum Gene Ther. 1993 Feb;4(1):1-2. doi: 10.1089/hum.1993.4.1-1. No abstract available.

  PMID: 8461379 BACKGROUND

• 2nd Euregenethy Multidisciplinary Forum on Regulatory and Safety Issues in Gene Therapy. June 9-11, 2000. Paris, France. Abstracts. J Gene Med. 2000;2(4 Suppl):1-47. No abstract available.

  PMID: 10979487 BACKGROUND

• Adam E, Nasz I. [Adenovirus vectors and their clinical application in gene therapy]. Orv Hetil. 2001 Sep 23;142(38):2061-70. Hungarian.

  PMID: 11697063 BACKGROUND

MeSH Terms

Conditions

Intermittent Claudication; Arteriosclerosis; Peripheral Arterial Disease; Peripheral Vascular Diseases

Condition Hierarchy (Ancestors)

Vascular Diseases; Cardiovascular Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Arterial Occlusive Diseases; Atherosclerosis

Study Design

• Study Type: interventional
• Phase: phase 1
• Purpose: TREATMENT
• Sponsor Type: NIH

Study Record Dates

• First Submitted: March 30, 2004
• First Posted: March 30, 2004
• Study Start: March 27, 2004
• Study Completion: December 29, 2011
• Last Updated: December 12, 2019

Record last verified: 2011-12-29

Locations

US (3)