Intracoronary Bradykinin Mediated t-PA Release in Heart Transplant Recipients

NCT00780377 | Withdrawn DMC

• 1 other identifier: 080823
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

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).

Conditions

Heart Transplantation

Keywords

Heart Transplant; Fibrinolysis; Resting conditions

Outcome Measures

Primary Outcomes (1)

• T-PA release in the coronary artery bed.

  Single Study Visit

Secondary Outcomes (2)

• Heart rate variability

  Single study visit

• Histopathology for arteriolar t-PA and sympathetic neurons

  Single Study Visit

Study Arms (1)

Bradykinin

EXPERIMENTAL

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

Interventions

Bradykinin DRUG

Bradykinin 0, 0.2, 0.6, 2.0 ug/min intracoronary, for 5 minutes at each dose.

Bradykinin

Eligibility Criteria

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

You may qualify if:

• 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)
• Subjects will have transplant vasculopathy and 25 subjects will be free of transplant vasculopathy, as documented in previous angiograms.
• Otherwise 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 A S AS Muldowney, MD

  Vanderbilt University Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

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: March 20, 2017

Record last verified: 2017-03

Locations

US (1)