Brachial Artery t-PA Release in Heart Transplant Recipients - Full Text View

Sponsor:	Vanderbilt University
Information provided by:	Vanderbilt University
ClinicalTrials.gov Identifier:	NCT00780637

Purpose

Bradykinin stimulates t-PA release from intact vessels, but not from endothelial cells in culture. It has been proposed that the nerves of blood vessels are the source of bradykinin stimulated t-PA release. In order tho test this hypothesis, we intend to infuse bradykinin into the brachial (arm) artery and the coronary arteries of heart transplant recipients and control subjects. This is because heart transplant recipients do not have nerves to their coronary arteries.

This protocol studies the effects of bradykinin on t-PA release in the forearm of transplant recipients. The brachial artery has intact nerves.

Separate protocols address coronary artery infusions in healthy subjects and transplant recipients and forearm infusions in healthy subjects.

Condition	Intervention
Heart Transplantation	Drug: Bradykinin

Vanderbilt University has indicated that access to an investigational treatment associated with this study is available outside the clinical trial.

Study Type:	Interventional
Study Design:	Allocation: Non-Randomized Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Basic Science
Official Title:	Characterization of Brachial Arterial t-PA Release, Vasodilator Function, and Vascular Compliance and Correlation With Fibrinolytic Balance, Oxidative Stress, and Inflammation Measures in Heart Transplant Recipients (SCCOR Project 1, Aim 3C)

Resource links provided by NLM:

MedlinePlus related topics: Heart Transplantation

Drug Information available for: Alteplase Tissue-type plasminogen activator

U.S. FDA Resources

Further study details as provided by Vanderbilt University:

Primary Outcome Measures:

Peak t-PA release [ Time Frame: Single Study Visit ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

t-PA release at various doses [ Time Frame: Single Study Visit ] [ Designated as safety issue: No ]

Estimated Enrollment:	100
Study Start Date:	October 2008
Estimated Study Completion Date:	May 2011
Estimated Primary Completion Date:	January 2011 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Bradykinin Patients receive 0, 10, 20, and 40 ng/min/100cc forearm volume of intrabrachial bradykinin, for 5 minutes at each dose. Forearm blood flow will be measured by strain gauge plethysmography, blood samples will be obtained to measure t-PA, PAI-1 at each dose. FMD and Radial artery tonometry will also be performed under resting conditions.	Drug: Bradykinin Patients receive 0, 10, 20, and 40 ng/100cc forearm volume/min of bradykinin intrabrachial.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion criteria:

Adults 18 years and greater who have undergone heart transplantation
Healthy

Exclusion criteria:

PVC < 30
Hypertensive subjects on ACE inhibitors
Pregnant or nursing mothers
Diabetic with HbA1C > 7.5 or stigmata of end organ damage (neuropathy, retinopathy, nephropathy, cardiomyopathy)
Cholesterol > 30 mg/dL above NCEP accepted level based on cardiac risk.
Triglycerides > 200
Previously diagnosed obstructive coronary artery disease
Renal insufficiency (Creatinine ≥ 1.5 mg/dl)
History of cerebrovascular disease
Any chronic inflammatory disease (rheumatologic, inflammatory bowel disease, etc)
Uncontrolled Stage 2 Hypertension (160/100 mmHg), or end organ damage due to hypertension (left ventricular hypertrophy, atrial fibrillation, hematuria, renal insufficiency, prior cerebrovascular disease).
Angiotensin converting enzyme inhibitor use
Coagulopathy (INR ≥ 1.5, PTT ≥ 150% of control)
Peripheral Vascular Disease
Other chronic medical illnesses at the discretion of the investigators

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00780637

Locations

United States, Tennessee
Vanderbilt University Medical Center
Nashville, Tennessee, United States, 37232

Sponsors and Collaborators

Vanderbilt University

Investigators

Principal Investigator:

James AS Muldowney, MD

Vanderbilt University

More Information

No publications provided

Responsible Party:	James Muldowney, M.D., F.A.C.C., Assistant Professor of Medicine, Vanderbilt University School of Medicine
ClinicalTrials.gov Identifier:	NCT00780637 History of Changes
Other Study ID Numbers:	070517
Study First Received:	October 24, 2008
Last Updated:	June 24, 2009
Health Authority:	United States: Food and Drug Administration

Keywords provided by Vanderbilt University:

Heart Transplant
Endothelial Function
Fibrinolysis
Transplant recipients at baseline

Additional relevant MeSH terms:

Bradykinin
Kininogens
Vasodilator Agents
Cardiovascular Agents
Therapeutic Uses

Pharmacologic Actions
Cysteine Proteinase Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on February 09, 2012