Protocol Number: 04-H-0143

Title:

Modulation of Vascular Endothelial Growth Factor (VEGF) Using an Engineered Zinc-Finger Transcription Factor to Treat Lower Limb Intermittent Claudication

Number:

04-H-0143

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.

Sponsoring Institute:

National Heart, Lung and Blood Institute (NHLBI)

Recruitment Detail

Type: No longer recruiting/follow-up only

Gender: Male & Female

Referral Letter Required: No

Population Exclusion(s): Children

Eligibility Criteria: This study is not currently recruiting new subjects. If you have questions about participating in a study, please contact the Patient Recruitment and Public Liaison Office, CC.

Special Instructions:

Currently Not Provided

Keyword(s):

Gene Transfer

Therapeutic Angiogenesis

Peripheral Arterial Disease

Perfusion

Magnetic Resonance Imaging

Peripheral Vascular Disease

Recruitment Keyword(s):

Claudication

PAD

Leg Claudication

Intermittent Claudication

Condition(s):

Intermittent Claudication

Arteriosclerosis

Investigational Drug(s):

EW-A-401 DNA Plasmid Vector

Investigational Device(s):

None

Interventions:

Drug: DNA Plasmid Vector

Drug: EW-A-401 DNA Plasmid Vector

Supporting Site:

National Heart, Lung and Blood Institute

Contact(s):

This study is not currently recruiting new subjects. If you have questions about participating in a study, please contact the Patient Recruitment and Public Liaison Office, CC.

Citation(s):

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

[No authors listed] 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.

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

• Questions about participating in a study, please contact the Patient Recruitment and Public Liaison Office, CC.
• Technical questions regarding the Clinical Center web site, please contact the Department Clinical Research Informatics, CC.

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