Brachial Artery t-PA Release in Heart Transplant Recipients

NCT00780637 | Withdrawn DMC

• 1 other identifier: 070517
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Heart Transplantation

Keywords

Heart Transplant; Endothelial Function; Fibrinolysis; Transplant recipients at baseline

Outcome Measures

Primary Outcomes (1)

• Peak t-PA release

  Single Study Visit

Secondary Outcomes (1)

• t-PA release at various doses

  Single Study Visit

Study Arms (1)

Bradykinin

EXPERIMENTAL

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

Interventions

Bradykinin DRUG

Patients receive 0, 10, 20, and 40 ng/100cc forearm volume/min of bradykinin intrabrachial.

Bradykinin

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Adults 18 years and greater who have undergone heart transplantation
• Healthy

You may not qualify if:

• 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

Sponsors & Collaborators

• Vanderbilt University: lead

Study Sites (1)

Vanderbilt University Medical Center

Nashville, Tennessee, 37232, United States

Location

MeSH Terms

Interventions

Bradykinin

Intervention Hierarchy (Ancestors)

Kinins; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Neuropeptides; Oligopeptides; Proteins; Nerve Tissue Proteins; Autacoids; Inflammation Mediators; Biological Factors

Study Officials

• James AS Muldowney, MD

  Vanderbilt University Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor of Medicine
• Expanded Access: Yes

Study Record Dates

• First Submitted: October 24, 2008
• First Posted: October 27, 2008
• Study Start: October 1, 2008
• Primary Completion: January 1, 2011
• Study Completion: May 1, 2011
• Last Updated: July 15, 2016

Record last verified: 2016-07

Locations

US (1)