Intracoronary Bradykinin Mediated t-PA Release in Heart Transplant Recipients (P1A4D)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00780377
Recruitment Status : Withdrawn (Unable to perform study due to unavailable drug, then unable to partner with cath lab)
First Posted : October 27, 2008
Last Update Posted : March 20, 2017
Information provided by (Responsible Party):
James Muldowney, Vanderbilt University Medical Center

Brief Summary:

Heart transplant recipients do not have nerves to their hearts. This protocol tests the hypothesis that bradykinin mediated t-PA release in the coronary arteries will be reduced in heart transplant recipients compared to healthy subjects.

This study will compare heart transplant recipients to healthy controls who are undergoing cardiac cath for standard of care purposes (separate protocol) and compare the coronary arteries to the forearm in transplant recipients (separate protocol) and healthy controls (separate protocol).

Condition or disease Intervention/treatment Phase
Heart Transplantation Drug: Bradykinin Not Applicable

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 0 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Basic Science
Official Title: The Effects of Cardiac Innervation on Intra-coronary t-PA Release
Actual Study Start Date : October 2008
Actual Primary Completion Date : January 2011
Actual Study Completion Date : May 2011

Resource links provided by the National Library of Medicine

U.S. FDA Resources

Arm Intervention/treatment
Experimental: Bradykinin
Patients have holter monitoring. Patients receive intracoronary bradykinin (0.2, 0.6, 2.0 ug/min) and have coronary sinus and coronary artery blood sampling for t-PA and O2 content.
Drug: Bradykinin
Bradykinin 0, 0.2, 0.6, 2.0 ug/min intracoronary, for 5 minutes at each dose.

Primary Outcome Measures :
  1. T-PA release in the coronary artery bed. [ Time Frame: Single Study Visit ]

Secondary Outcome Measures :
  1. Heart rate variability [ Time Frame: Single study visit ]
  2. Histopathology for arteriolar t-PA and sympathetic neurons [ Time Frame: Single Study Visit ]

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion criteria:

  1. Heart transplant recipients undergoing annual cardiac catheterization who have participated our protocol: 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). (IRB # 070517)
  2. 25 Subjects will have transplant vasculopathy and 25 subjects will be free of transplant vasculopathy, as documented in previous angiograms.
  3. Otherwise 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

Healthy controls are being enrolled in SCCOR Project 1, Aims 3A and 3B (IRB# 030473 and 061160) and will not be participating under this IRB number.

Information from the National Library of Medicine

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 identifier (NCT number): NCT00780377

United States, Tennessee
Vanderbilt University Medical Center
Nashville, Tennessee, United States, 37232
Sponsors and Collaborators
Vanderbilt University
Principal Investigator: James A S AS Muldowney, MD Vanderbilt University Medical Center

Responsible Party: James Muldowney, Assistant Professor, Vanderbilt University Medical Center Identifier: NCT00780377     History of Changes
Other Study ID Numbers: 080823
First Posted: October 27, 2008    Key Record Dates
Last Update Posted: March 20, 2017
Last Verified: March 2017

Keywords provided by James Muldowney, Vanderbilt University Medical Center:
Heart Transplant
Resting conditions

Additional relevant MeSH terms:
Vasodilator Agents
Cysteine Proteinase Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action