Brachial Artery t-PA Release in Heart Transplant Recipients (P1A3C)

This study is enrolling participants by invitation only.
Sponsor:
Information provided by:
Vanderbilt University
ClinicalTrials.gov Identifier:
NCT00780637
First received: October 24, 2008
Last updated: June 24, 2009
Last verified: June 2009
  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:


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:

  1. Adults 18 years and greater who have undergone heart transplantation
  2. Healthy

Exclusion criteria:

  1. PVC < 30
  2. Hypertensive subjects on ACE inhibitors
  3. Pregnant or nursing mothers
  4. Diabetic with HbA1C > 7.5 or stigmata of end organ damage (neuropathy, retinopathy, nephropathy, cardiomyopathy)
  5. Cholesterol > 30 mg/dL above NCEP accepted level based on cardiac risk.
  6. Triglycerides > 200
  7. Previously diagnosed obstructive coronary artery disease
  8. Renal insufficiency (Creatinine ≥ 1.5 mg/dl)
  9. History of cerebrovascular disease
  10. Any chronic inflammatory disease (rheumatologic, inflammatory bowel disease, etc)
  11. 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).
  12. Angiotensin converting enzyme inhibitor use
  13. Coagulopathy (INR ≥ 1.5, PTT ≥ 150% of control)
  14. Peripheral Vascular Disease
  15. Other chronic medical illnesses at the discretion of the investigators
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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 September 16, 2014