Endothelial Hyperpolarization in Humans
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ClinicalTrials.gov Identifier: NCT00166166 |
Recruitment Status :
Terminated
(Limited clinical staff)
First Posted : September 14, 2005
Results First Posted : May 13, 2015
Last Update Posted : August 15, 2018
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Condition or disease | Intervention/treatment | Phase |
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Hyperlipidemia | Drug: Tetraethylammonium (TEA) Drug: L-NG-monomethyl Arginine (L-NMMA) Drug: Bradykinin Drug: Sodium nitroprusside Drug: Acetylcholine Drug: Saline Drug: Fluconazole | Phase 2 |
Study Type : | Interventional (Clinical Trial) |
Actual Enrollment : | 174 participants |
Allocation: | Non-Randomized |
Intervention Model: | Single Group Assignment |
Masking: | None (Open Label) |
Primary Purpose: | Diagnostic |
Official Title: | Physiology and Pathologic Role of Endothelium-Derived Hyperpolarizing Factor in Humans |
Study Start Date : | July 2002 |
Actual Primary Completion Date : | January 2013 |
Actual Study Completion Date : | January 2013 |
Arm | Intervention/treatment |
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Experimental: Healthy Controls
Healthy subjects had venous occlusion plethysmography after intra-arterial infusions of saline, L-NG-monomethyl Arginine (L-NMMA), Tetraethylammonium (TEA), fluconazole, bradykinin, sodium nitroprusside and acetylcholine
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Drug: Tetraethylammonium (TEA)
5 minute intra-arterial infusion of Tetraethylammonium at 1 mg/min Drug: L-NG-monomethyl Arginine (L-NMMA) 5 minute intra-arterial infusion of L-NMMA 8 μmol/min
Other Name: Methylarginine Drug: Bradykinin Intra-arterial infusion of bradykinin at 100, 200, and 400 ng/min. Each dose will be given for 5 minutes. Drug: Sodium nitroprusside Intra-arterial infusion of sodium nitroprusside at 1.6 and 3.2 mg/min. Each dose will be given for 5 minutes.
Other Name: Nitropress Drug: Acetylcholine Intra-arterial infusion of acetylcholine at 7.5, 15 and 30 μg/min. Each dose will be given for 5 minutes. Drug: Saline 5 minute intra-arterial infusion of 0.9% saline at 2.5ml/min Drug: Fluconazole 5 minute intra-arterial infusion of fluconazole at 0.4 mg/L/min
Other Name: Diflucan |
Experimental: Risk Factors
Non-hypertensive subjects with cardiovascular risk factors had venous occlusion plethysmography after intra-arterial infusions of saline, L-NG-monomethyl Arginine (L-NMMA), Tetraethylammonium (TEA), fluconazole, bradykinin, sodium nitroprusside and acetylcholine
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Drug: Tetraethylammonium (TEA)
5 minute intra-arterial infusion of Tetraethylammonium at 1 mg/min Drug: L-NG-monomethyl Arginine (L-NMMA) 5 minute intra-arterial infusion of L-NMMA 8 μmol/min
Other Name: Methylarginine Drug: Bradykinin Intra-arterial infusion of bradykinin at 100, 200, and 400 ng/min. Each dose will be given for 5 minutes. Drug: Sodium nitroprusside Intra-arterial infusion of sodium nitroprusside at 1.6 and 3.2 mg/min. Each dose will be given for 5 minutes.
Other Name: Nitropress Drug: Acetylcholine Intra-arterial infusion of acetylcholine at 7.5, 15 and 30 μg/min. Each dose will be given for 5 minutes. Drug: Saline 5 minute intra-arterial infusion of 0.9% saline at 2.5ml/min Drug: Fluconazole 5 minute intra-arterial infusion of fluconazole at 0.4 mg/L/min
Other Name: Diflucan |
- Percent Change in Forearm Blood Flow (FBF) After Tetraethylammonium (TEA) Administration [ Time Frame: Baseline, 5 minutes ]Simultaneous forearm blood flow (FBF) measurements were obtained in both arms using a dual-channel venous occlusion strain gauge plethysmograph at rest and after administration of tetraethylammonium (TEA). Flow measurements were recorded for approximately 7 seconds, every 15 seconds up to eight times and a mean FBF value was computed. Percent change is the difference from baseline FBF and after TEA administration.
- Percent Change in Forearm Blood Flow (FBF) After Administration of L-NG-monomethyl Arginine (L-NMMA) [ Time Frame: Baseline, 5 minutes ]Simultaneous forearm blood flow (FBF) measurements were obtained in both arms using a dual-channel venous occlusion strain gauge plethysmograph after administration of L-NG-monomethyl Arginine (L-NMMA). Flow measurements were recorded for approximately 7 seconds, every 15 seconds up to eight times and a mean FBF value was computed. Percent change is the difference in FBF from baseline and after L-NMMA administration.
- Percent Change in Forearm Blood Flow (FBF) After Administration of L-NG-monomethyl Arginine (L-NMMA) and Tetraethylammonium (TEA) [ Time Frame: 5 minutes, 10 minutes ]Simultaneous forearm blood flow (FBF) measurements were obtained in both arms using a dual-channel venous occlusion strain gauge plethysmograph after administration of L-NG-monomethyl Arginine (L-NMMA) and Tetraethylammonium (TEA). Flow measurements were recorded for approximately 7 seconds, every 15 seconds up to eight times and a mean FBF value was computed. Percent change is the difference in FBF from after L-NMMA administration and after TEA administration.
- Percent Change in Forearm Blood Flow (FBF) After Fluconazole Administration [ Time Frame: Baseline, 5 minutes ]Simultaneous forearm blood flow (FBF) measurements were obtained in both arms using a dual-channel venous occlusion strain gauge plethysmograph at rest and after administration of fluconazole. Flow measurements were recorded for approximately 7 seconds, every 15 seconds up to eight times and a mean FBF value was computed. Percent change is the difference from baseline FBF and after fluconazole administration.
- Percent Change in Forearm Blood Flow (FBF) After L-NG-monomethyl Arginine (L-NMMA) and Fluconazole Administration [ Time Frame: 5 minutes, 10 minutes ]Simultaneous forearm blood flow (FBF) measurements were obtained in both arms using a dual-channel venous occlusion strain gauge plethysmograph after L-NMMA administration and administration of fluconazole. Flow measurements were recorded for approximately 7 seconds, every 15 seconds up to eight times and a mean FBF value was computed. Percent change is the difference in FBF after L-NMMA administration and then fluconazole administration.
- Percent Change in Forearm Blood Flow (FBF) After Fluconazole and Tetraethylammonium (TEA) Administration [ Time Frame: 5 minutes, 10 minutes ]Simultaneous forearm blood flow (FBF) measurements were obtained in both arms using a dual-channel venous occlusion strain gauge plethysmograph after administration of fluconazole and Tetraethylammonium (TEA) administration. Flow measurements were recorded for approximately 7 seconds, every 15 seconds up to eight times and a mean FBF value was computed. Percent change is the difference from FBF after fluconazole administration and after Tetraethylammonium (TEA) administration.
- Forearm Blood Flow (FBF) After Sodium Nitroprusside Administration [ Time Frame: 5 minutes ]Simultaneous forearm blood flow (FBF) measurements were obtained in both arms using a dual-channel venous occlusion strain gauge plethysmograph after administration of sodium nitroprusside. Flow measurements were recorded for approximately 7 seconds, every 15 seconds up to eight times and a mean FBF value was computed.
- Change in Tissue Plasminogen Activator (t-PA) Release [ Time Frame: Baseline, 30 minutes ]Individual net t-PA release at each time point were calculated by the following formula: net release = (Cv-CA) x {FBF x [101-hematocrit/100]}, where Cv and CA represent the concentration of t-PA in the brachial vein and artery, respectively. Change is the difference of t-PA at baseline and t-PA after bradykinin 400 ng/min
- Change in Tissue Plasminogen Activator (t-PA) Release After Tetraethylammonium (TEA) and Bradykinin Administration [ Time Frame: 30 minutes, 60 minutes ]Individual net t-PA release at each time point were calculated by the following formula: net release = (Cv-CA) x {FBF x [101-hematocrit/100]}, where Cv and CA represent the concentration of t-PA in the brachial vein and artery, respectively. Change is the difference of t-PA after Tetraethylammonium (TEA) and t-PA after bradykinin 400 ng/min
- Change in Tissue Plasminogen Activator (t-PA) Release After Fluconazole and Bradykinin Administration [ Time Frame: 30 minutes, 60 minutes ]Individual net t-PA release at each time point were calculated by the following formula: net release = (Cv-CA) x {FBF x [101-hematocrit/100]}, where Cv and CA represent the concentration of t-PA in the brachial vein and artery, respectively. Change is the difference of t-PA after fluconazole and t-PA after bradykinin 400 ng/min
- Change in Tissue Plasminogen Activator (t-PA) Release After Fluconazole, Tetraethylammonium (TEA), and Bradykinin Administration [ Time Frame: 60 minutes, 90 minutes ]Individual net t-PA release at each time point were calculated by the following formula: net release = (Cv-CA) x {FBF x [101-hematocrit/100]}, where Cv and CA represent the concentration of t-PA in the brachial vein and artery, respectively. Change is the difference of t-PA after fluconazole and tetraethylammonium (TEA) and t-PA after bradykinin 400 ng/min

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Ages Eligible for Study: | 21 Years to 65 Years (Adult, Older Adult) |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | Yes |
Inclusion Criteria:
- Hyperlipidemic (LDL > 140)
- Healthy Volunteer
Exclusion Criteria:
- Pregnancy
- Diabetes mellitus
- Cardiovascular Disease
- Hypertension
- Use of any regular medications
- Renal insufficiency
- Smoking (current or within the past 5 years)
- Bleeding disorder

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00166166
United States, Georgia | |
Emory University School of Medicine | |
Atlanta, Georgia, United States, 30322 |
Principal Investigator: | Arshed A Quyyumi, MD | Emory University School of Medicine, Division of Cardiology |
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: | Arshed A. Quyyumi, Professor, Emory University |
ClinicalTrials.gov Identifier: | NCT00166166 |
Other Study ID Numbers: |
IRB00021886 1R01HL079115-01 ( U.S. NIH Grant/Contract ) 0605-2002 ( Other Identifier: Other ) |
First Posted: | September 14, 2005 Key Record Dates |
Results First Posted: | May 13, 2015 |
Last Update Posted: | August 15, 2018 |
Last Verified: | July 2018 |
hyperlipidaemia EDHF FMD |
Hyperlipidemias Hyperlipoproteinemias Dyslipidemias Lipid Metabolism Disorders Metabolic Diseases Fluconazole Nitroprusside Tetraethylammonium Acetylcholine Bradykinin omega-N-Methylarginine Kininogens Antifungal Agents Anti-Infective Agents 14-alpha Demethylase Inhibitors |
Cytochrome P-450 Enzyme Inhibitors Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action Steroid Synthesis Inhibitors Hormone Antagonists Hormones, Hormone Substitutes, and Hormone Antagonists Physiological Effects of Drugs Cytochrome P-450 CYP2C9 Inhibitors Cytochrome P-450 CYP2C19 Inhibitors Antihypertensive Agents Vasodilator Agents Nitric Oxide Donors Cholinergic Agonists Cholinergic Agents Neurotransmitter Agents |