Effects of Miconazole on Blood Flow
Information source: National Institutes of Health Clinical Center (CC)
Information obtained from ClinicalTrials.gov on June 20, 2008
Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Healthy
Intervention: Miconazole, L-NMMA, Bradykinin (Drug)
Phase: Phase 1
Status: Completed
Sponsored by: National Heart, Lung, and Blood Institute (NHLBI)
Summary
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.
Clinical Details
Official title: Investigation of Miconazole as an Inhibitor of Endothelium-Derived Hyperpolarizing Factor
Study design: Treatment, Safety Study
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
Minimum age: N/A.
Maximum age: N/A.
Gender(s): Both.
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.
Locations and Contacts
National Heart, Lung and Blood Institute (NHLBI), Bethesda, Maryland 20892, United States
Additional Information
Related publications: Feletou M, Vanhoutte PM. Endothelium-derived hyperpolarizing factor. Clin Exp Pharmacol Physiol. 1996 Dec;23(12):1082-90. Review. Furchgott RF, Vanhoutte PM. Endothelium-derived relaxing and contracting factors. FASEB J. 1989 Jul;3(9):2007-18. Review. Keef KD, Bowen SM. Effect of ACh on electrical and mechanical activity in guinea pig coronary arteries. Am J Physiol. 1989 Oct;257(4 Pt 2):H1096-103.
Starting date: February 2000
Ending date: October 2001
Last updated: March 3, 2008
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