This study will evaluate the safety and bioactivity of intramuscular administration of a plasmid containing the cDNA for vascular endothelial growth factor (pVGI.1) to the extremities of patients with diabetic neuropathy and macrovascular disease.

Condition	Treatment or Intervention	Phase
Diabetic Neuropathy	Gene Transfer: pVGI.1	Phase I Phase II

Further Study Details: 

Expected Total Enrollment:  192

Ages Eligible for Study:  21 Years and above,  Genders Eligible for Study:  Both

Criteria

Inclusion criteria:

To be eligible to enroll and remain in the study, patients must meet the following criteria:

• Be at least 21 years old.
• Have type I or type II diabetes mellitus and require oral anti-hyperglycemic agents or insulin.
• Have clinical evidence of a predominantly sensory neuropathy (as determined by a Neurologist and by EMG).
• Have an ABI <0.90 in the affected leg; or, have previous evidence of peripheral arterial disease by plethysmography, angiography, or magnetic resonance angiography.
• Women of child-bearing potential must agree to use all means available not to become pregnant during the course of the study. Nonsterile men participating in the study must also agree to use all means available to prevent pregnancy in their partners.
• Have the ability to understand the requirements of the study, provide written informed consent, abide by the study restrictions, and agree to return for the required assessments.
• Agree to participate in follow-up.

Exclusion criteria

Patients are to be excluded from the trial if any of the following conditions are met:

• Have any concomitant disease that results in a life expectancy of less than 1 year or that is sufficiently severe to compromise clinical follow-up examinations.
• Have a history of alcohol or drug abuse within 3 months of screening.
• Have any evidence (clinical, laboratory, or imaging) or history of malignant neoplasm (other than non-melanoma skin carcinoma or in-situ cervical carcinoma) within the past five years, or cancer recurrence within the past five years.
• Have evidence of moderate to severe proliferative retinopathy on fundoscopic examination by an ophthalmologist.
• Have any clinically significant abnormality in liver function test (defined as a value more than 2 times the upper limit of the normal range for that value); or, have any other laboratory value of clinical significance, in the opinion of the investigator.
• Have undergone successful lower extremity surgical revascularization, percutaneous transluminal angioplasty, or lumbar sympathectomy within the 6 months preceding screening.
• Be a suitable candidate for surgical or angioplastic revascularization in the limb in which treatment is proposed.
• Is currently taking and/or unable to be withdrawn from any of the following therapies: prostaglandins, dextran, pentoxyfylline, L-carnitine, hyperbaric oxygen. (Patients are permitted to remain on risk factor modification therapy for their vascular disease provided they have been on a stable dose of these medications for at least 6 weeks prior to enrollment in the study and remain on these medications throughout the study period.)
• Be pregnant or lactating.
• Have > 3+ edema of the limb in which treatment is proposed.
• Have an amputated great toe (or great toe compromised by an ulcer) in the limb to be injected that would prevent neurological and quantitative sensory testing.
• Be unsuitable for participation in the study, in the opinion of the Investigator.

Massachusetts
      Caritas St. Elizabeth's Medical Center Cardiovascular Research/DVM-4-SMC, Boston,  Massachusetts,  02135,  United States; Recruiting

Study chairs or principal investigators

Allan H Ropper, M.D.,  Principal Investigator,  Caritas St. Elizabeth's Medical Center of Boston   

Study ID Numbers:  IRB #04010000; NIH #0104-467
Record last reviewed:  February 2005
Last Updated:  February 10, 2005
Record first received:  March 10, 2003
ClinicalTrials.gov Identifier:  NCT00056290
Health Authority: United States: Food and Drug Administration
ClinicalTrials.gov processed this record on 2005-04-08