Effects of Miconazole on Blood Flow

Investigation of Miconazole as an Inhibitor of Endothelium-Derived Hyperpolarizing Factor

This study will investigate the effect of the drug miconazole on blood vessel dilation. Miconazole stops production of EDHF, a substance that causes arteries to dilate. EDHF is produced by the cells that line blood vessels.

Normal volunteers between the ages of 21 to 60 may participate in this study. Candidates will be screened for eligibility with a medical history, physical examination, electrocardiogram and routine laboratory tests. Those enrolled will be injected with miconazole to study its effects on blood vessels.

Study participants will take three aspirin tablets. After administration of a local anesthetic, small tubes will be inserted through a needle into the artery and vein of the forearm. These will be used to measure blood pressure and to draw blood samples during the study. Forearm blood flow will be measured using pressure cuffs placed on the wrist and upper arm, and a strain gauge (a rubber band device) placed around the forearm. When the cuffs are inflated, blood will flow into the arm, stretching the strain gauge, and the flow measurement will be recorded.

Small doses of four drugs-bradykinin, sodium nitroprusside, miconazole, and LNMMA-will be given through the arterial catheter. Bradykinin stimulates the release of EDHF and can lower blood pressure. Sodium nitroprusside causes blood vessels to dilate and is used to treat high blood pressure and heart failure. Miconazole is commonly prescribed to treat various infections, including vaginal yeast infections, jock itch and athlete's foot. In much higher doses, it is used to treat fungal infections that have spread to the lungs, brain, kidneys, or bladder. LNMMA inhibits production of nitric oxide, another substance produced by the lining cells of blood vessels.

Blood flow will be measured throughout the study, which will last approximately 3 hours.

Study Overview

Status

Completed

Conditions

Detailed Description

The vascular endothelium synthesizes at least three potent vasodilator substances: nitric oxide (NO), prostacyclin and an endothelium-derived hyperpolarizing factor (EDHF). EDHF release is stimulated by receptor-dependent agonists such as acetylcholine and bradykinin (BK), and leads to hyperpolarization of the underlying smooth muscle cells presumably by opening Ca(2+)-activated K(+) channels. Indirect pharmacologic evidence suggests that EDHF is a cytochrome P450-derived arachidonic acid metabolite, presumably an epoxide.

Numerous inhibitors of EDHF have been defined in animal tissues. Of these, miconazole has proven to be safe when administered to humans as a topical and parenteral antifungal agent. At levels that are attained with routine clinical use, it has a rapid onset of action with high specificity of inhibition of EDHF in animal models. This study is designed to investigate the safety and efficacy of intra-arterial miconazole in inhibiting BK-mediated forearm vasodilation in normal volunteers.

Study Type

Interventional

Enrollment

15

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

    • Maryland
      • Bethesda, Maryland, United States, 20892
        • National Heart, Lung and Blood Institute (NHLBI)

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Child
  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Healthy male or female volunteers (age 21-60 years).

No presence of intercurrent illness.

No current smoking (within previous 5 years).

No hypertension (greater than 140/90).

No diabetes.

No hypercholesterolemia (total cholesterol greater than 240 mg/dl).

No pregnancy or menopause.

No renal failure (creatinine greater than 1.4 mg/dl).

No allergies to miconazole, parabens, castor oil or aspirin.

No bleeding disorders.

No consumption of any medications during the last one week, including vitamins and unconventional medications.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

February 1, 2000

Study Completion

October 1, 2001

Study Registration Dates

First Submitted

February 17, 2000

First Submitted That Met QC Criteria

May 21, 2002

First Posted (Estimate)

May 22, 2002

Study Record Updates

Last Update Posted (Estimate)

March 4, 2008

Last Update Submitted That Met QC Criteria

March 3, 2008

Last Verified

October 1, 2001

More Information

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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