Effects of Miconazole on Blood Flow

This study has been completed.
Sponsor:
Information provided by:
National Institutes of Health Clinical Center (CC)
ClinicalTrials.gov Identifier:
NCT00004575
First received: February 17, 2000
Last updated: March 3, 2008
Last verified: October 2001
  Purpose

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.


Condition Intervention Phase
Healthy
Drug: Miconazole, L-NMMA, Bradykinin
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Primary Purpose: Treatment
Official Title: Investigation of Miconazole as an Inhibitor of Endothelium-Derived Hyperpolarizing Factor

Resource links provided by NLM:


Further study details as provided by National Institutes of Health Clinical Center (CC):

Estimated Enrollment: 15
Study Start Date: February 2000
Estimated Study Completion Date: October 2001
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.

  Eligibility

Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

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.

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00004575

Locations
United States, Maryland
National Heart, Lung and Blood Institute (NHLBI)
Bethesda, Maryland, United States, 20892
Sponsors and Collaborators
  More Information

Publications:
ClinicalTrials.gov Identifier: NCT00004575     History of Changes
Other Study ID Numbers: 000077, 00-H-0077
Study First Received: February 17, 2000
Last Updated: March 3, 2008
Health Authority: United States: Federal Government

Keywords provided by National Institutes of Health Clinical Center (CC):
Endothelium
Vasodilation
Vascular Biology
Venous Occlusion Plethysmography

Additional relevant MeSH terms:
Bradykinin
Miconazole
Clotrimazole
Vasodilator Agents
Cardiovascular Agents
Therapeutic Uses
Pharmacologic Actions
Antifungal Agents
Anti-Infective Agents
14-alpha Demethylase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Anti-Infective Agents, Local

ClinicalTrials.gov processed this record on July 20, 2014