NCT00166166

Brief Summary

The purpose of this study is to elucidate the role Endothelium-Derived Hyperpolarizing Factor (EDHF) plays in dilating blood vessels and whether it differs between healthy people and those with high cholesterol. A second purpose of the study is to determine the identity of EDHF.

Trial Health

57
Monitor

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
174

participants targeted

Target at P75+ for phase_2

Timeline
Completed

Started Jul 2002

Longer than P75 for phase_2

Geographic Reach
1 country

1 active site

Status
terminated

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

July 1, 2002

Completed
3.2 years until next milestone

First Submitted

Initial submission to the registry

September 13, 2005

Completed
1 day until next milestone

First Posted

Study publicly available on registry

September 14, 2005

Completed
7.3 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

January 1, 2013

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

January 1, 2013

Completed
2.4 years until next milestone

Results Posted

Study results publicly available

May 13, 2015

Completed
Last Updated

August 15, 2018

Status Verified

July 1, 2018

Enrollment Period

10.5 years

First QC Date

September 13, 2005

Results QC Date

May 8, 2015

Last Update Submit

July 17, 2018

Conditions

Hyperlipidemia

Keywords

hyperlipidaemiaEDHFFMD

Outcome Measures

Primary Outcomes (2)

  • Percent Change in Forearm Blood Flow (FBF) After Tetraethylammonium (TEA) Administration

    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.

    Baseline, 5 minutes

  • Percent Change in Forearm Blood Flow (FBF) After Administration of L-NG-monomethyl Arginine (L-NMMA)

    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.

    Baseline, 5 minutes

Secondary Outcomes (9)

  • Percent Change in Forearm Blood Flow (FBF) After Administration of L-NG-monomethyl Arginine (L-NMMA) and Tetraethylammonium (TEA)

    5 minutes, 10 minutes

  • Percent Change in Forearm Blood Flow (FBF) After Fluconazole Administration

    Baseline, 5 minutes

  • Percent Change in Forearm Blood Flow (FBF) After L-NG-monomethyl Arginine (L-NMMA) and Fluconazole Administration

    5 minutes, 10 minutes

  • Percent Change in Forearm Blood Flow (FBF) After Fluconazole and Tetraethylammonium (TEA) Administration

    5 minutes, 10 minutes

  • Forearm Blood Flow (FBF) After Sodium Nitroprusside Administration

    5 minutes

  • +4 more secondary outcomes

Study Arms (2)

Healthy Controls

EXPERIMENTAL

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

Drug: Tetraethylammonium (TEA)Drug: L-NG-monomethyl Arginine (L-NMMA)Drug: BradykininDrug: Sodium nitroprussideDrug: AcetylcholineDrug: SalineDrug: Fluconazole

Risk Factors

EXPERIMENTAL

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

Drug: Tetraethylammonium (TEA)Drug: L-NG-monomethyl Arginine (L-NMMA)Drug: BradykininDrug: Sodium nitroprussideDrug: AcetylcholineDrug: SalineDrug: Fluconazole

Interventions

Tetraethylammonium (TEA)DRUG

5 minute intra-arterial infusion of Tetraethylammonium at 1 mg/min

Healthy ControlsRisk Factors
L-NG-monomethyl Arginine (L-NMMA)DRUG

5 minute intra-arterial infusion of L-NMMA 8 μmol/min

Also known as: Methylarginine
Healthy ControlsRisk Factors
BradykininDRUG

Intra-arterial infusion of bradykinin at 100, 200, and 400 ng/min. Each dose will be given for 5 minutes.

Healthy ControlsRisk Factors
Sodium nitroprussideDRUG

Intra-arterial infusion of sodium nitroprusside at 1.6 and 3.2 mg/min. Each dose will be given for 5 minutes.

Also known as: Nitropress
Healthy ControlsRisk Factors
AcetylcholineDRUG

Intra-arterial infusion of acetylcholine at 7.5, 15 and 30 μg/min. Each dose will be given for 5 minutes.

Healthy ControlsRisk Factors
SalineDRUG

5 minute intra-arterial infusion of 0.9% saline at 2.5ml/min

Healthy ControlsRisk Factors
FluconazoleDRUG

5 minute intra-arterial infusion of fluconazole at 0.4 mg/L/min

Also known as: Diflucan
Healthy ControlsRisk Factors

Eligibility Criteria

Age21 Years - 65 Years
Sexall
Healthy VolunteersYes
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Hyperlipidemic (LDL \> 140)
  • Healthy Volunteer

You may not qualify if:

  • Pregnancy
  • Diabetes mellitus
  • Cardiovascular Disease
  • Hypertension
  • Use of any regular medications
  • Renal insufficiency
  • Smoking (current or within the past 5 years)
  • Bleeding disorder

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Emory University School of Medicine

Atlanta, Georgia, 30322, United States

Location

Related Publications (4)

  • Ozkor MA, Murrow JR, Rahman AM, Kavtaradze N, Lin J, Manatunga A, Quyyumi AA. Endothelium-derived hyperpolarizing factor determines resting and stimulated forearm vasodilator tone in health and in disease. Circulation. 2011 May 24;123(20):2244-53. doi: 10.1161/CIRCULATIONAHA.110.990317. Epub 2011 May 9.

    PMID: 21555712RESULT

  • Ozkor MA, Hayek SS, Rahman AM, Murrow JR, Kavtaradze N, Lin J, Manatunga A, Quyyumi AA. Contribution of endothelium-derived hyperpolarizing factor to exercise-induced vasodilation in health and hypercholesterolemia. Vasc Med. 2015 Feb;20(1):14-22. doi: 10.1177/1358863X14565374. Epub 2015 Feb 3.

    PMID: 25648989DERIVED

  • Rahman AM, Murrow JR, Ozkor MA, Kavtaradze N, Lin J, De Staercke C, Hooper WC, Manatunga A, Hayek S, Quyyumi AA. Endothelium-derived hyperpolarizing factor mediates bradykinin-stimulated tissue plasminogen activator release in humans. J Vasc Res. 2014;51(3):200-8. doi: 10.1159/000362666. Epub 2014 Jun 4.

    PMID: 24925526DERIVED

  • Ozkor MA, Rahman AM, Murrow JR, Kavtaradze N, Lin J, Manatunga A, Hayek S, Quyyumi AA. Differences in vascular nitric oxide and endothelium-derived hyperpolarizing factor bioavailability in blacks and whites. Arterioscler Thromb Vasc Biol. 2014 Jun;34(6):1320-7. doi: 10.1161/ATVBAHA.113.303136. Epub 2014 Mar 27.

    PMID: 24675657DERIVED

MeSH Terms

Conditions

Hyperlipidemias

Interventions

Tetraethylammoniumomega-N-MethylarginineBradykininNitroprussideAcetylcholineSodium ChlorideFluconazole

Condition Hierarchy (Ancestors)

DyslipidemiasLipid Metabolism DisordersMetabolic DiseasesNutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Tetraethylammonium CompoundsQuaternary Ammonium CompoundsAminesOrganic ChemicalsOnium CompoundsArginineAmino Acids, BasicAmino AcidsAmino Acids, Peptides, and ProteinsAmino Acids, DiaminoAmino Acids, EssentialKininsIntercellular Signaling Peptides and ProteinsPeptidesNeuropeptidesOligopeptidesProteinsNerve Tissue ProteinsAutacoidsInflammation MediatorsBiological FactorsFerricyanidesCyanidesAnionsIonsElectrolytesInorganic ChemicalsFerric CompoundsIron CompoundsHydrogen CyanideNitrogen CompoundsBiogenic AminesChloridesHydrochloric AcidChlorine CompoundsSodium CompoundsTriazolesAzolesHeterocyclic Compounds, 1-RingHeterocyclic Compounds

Limitations and Caveats

Findings are limited to the forearm microcirculations, thus other vascular beds including conductance arteries warrant further investigation. Nevertheless, it is known that the contribution of EDHF is less in conductance vessels than in microvessels.

Results Point of Contact

Title
Dr. Arshed Quyyumi
Organization
Emory University
aquyyum@emory.edu
404-727-3655

Study Officials

  • Arshed A Quyyumi, MD

    Emory University School of Medicine, Division of Cardiology

    PRINCIPAL INVESTIGATOR

Publication Agreements

PI is Sponsor Employee
Yes

Study Design

Study Type
interventional
Phase
phase 2
Allocation
NON RANDOMIZED
Masking
NONE
Purpose
DIAGNOSTIC
Intervention Model
SINGLE GROUP
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Professor

Study Record Dates

First Submitted

September 13, 2005

First Posted

September 14, 2005

Study Start

July 1, 2002

Primary Completion

January 1, 2013

Study Completion

January 1, 2013

Last Updated

August 15, 2018

Results First Posted

May 13, 2015

Record last verified: 2018-07

Locations

US(1)