Imaging Inducible Nitric Oxide Synthase (iNOS)Activity Using F-NOS Tracer.

The recruitment status of this study is unknown because the information has not been verified recently.
Verified May 2011 by Washington University School of Medicine.
Recruitment status was  Recruiting
Sponsor:
Information provided by:
Washington University School of Medicine
ClinicalTrials.gov Identifier:
NCT01066637
First received: February 8, 2010
Last updated: May 11, 2011
Last verified: May 2011
  Purpose

The primary purpose of this study is to measure the level of an enzyme in a patient's heart called inducible nitric oxide synthase(iNOS) using Positron Emission Tomography (PET) imaging with a radioactive tracer called F-NOS. These Pet results will be compared to tissue results obtained during routine endomyocardial heart biopsy. The enzyme iNOS produces nitric oxide in inflammatory diseases such as acute heart transplant rejection, diabetes, Alzheimer's and cancer. Thus, PET with the radioactive tracer F-NOS may be a useful tool for detecting the early stages of these diseases. The safety of F-NOS during the study will also be assessed.


Condition
Heart Transplantation

Study Type: Observational
Study Design: Observational Model: Case-Only
Time Perspective: Prospective
Official Title: Imaging Inducible Nitric Oxide Synthase (iNOS)Activity Using F-NOS Tracer With Positron Emission Tomography (PET) in Cellular Inflammation.

Resource links provided by NLM:


Further study details as provided by Washington University School of Medicine:

Biospecimen Retention:   Samples With DNA

Blood and Urine samples for lab testing


Estimated Enrollment: 28
Study Start Date: September 2009
Estimated Study Completion Date: December 2011
Estimated Primary Completion Date: September 2011 (Final data collection date for primary outcome measure)
Groups/Cohorts
Heart Transplantation patients
Patients 21 years of age or older of either sex, who are status-post heart transplant and normal healthy volunteers (2 women and 2 men) will be enrolled.

Detailed Description:

Nitric oxide (NO) is an important and unique mediator of a variety of physiological and pathological processes. NO is generated from the oxidation of L-arginine to L-citrulline in a two-step process by nitric oxide synthase (NOS) enzymes. In the NOS family, there are two constitutive isozymes of NOS, neuronal NOS (nNOS) and endothelial NOS (eNOS), and one inducible isozyme (iNOS). The three isozymes of NOS are expressed in different tissues to generate NO for specific physiological roles. nNOS generates NO as a neurotransmitter and neuromodulator, mainly in brain and peripheral nerve cells; eNOS regulates blood pressure, and blood flow primarily in vascular endothelial cells. The induction of iNOS occurs by various inflammatory stimuli (e.g., endotoxin) in activated macrophages and other types of cells and plays a crucial role in the host defense and the inflammatory processes.

Normally, the basal level of NO in all parts of the body is very low, mainly due to the constitutive nNOS and eNOS. In contrast, once expressed, iNOS can continue to generate NO in large amounts (up to μM concentrations) for a prolonged period of time. Studies have shown that production of NO by iNOS is implicated in a variety of acute and chronic inflammatory diseases (e.g., sepsis, septic shock, organ transplant rejection, vascular dysfunction in diabetes, asthma, arthritis, multiple sclerosis, and inflammatory diseases of the gut). iNOS activity has also been found in many tumors. Because of the central role of iNOS in NO-related diseases, numerous efforts have been made to develop iNOS inhibitors as pharmaceuticals ranging from the nonselective L-arginine analogues to the selective inhibitors reported recently. Some inhibitors of iNOS have shown promising results in animal models of sepsis, lung inflammation, arthritis, and autoimmune diabetes. Therefore, the development of a radiolabeled iNOS inhibitor for probing iNOS expression in vivo using noninvasive positron emission tomography (PET) imaging will be of tremendous value to the study and treatment of NO-related diseases.

Acute allograft rejection is the major contributor to mortality in patients receiving orthotopic heart transplantation (OHT). Specifically, iNOS has been thought to be the main NOS involved in producing NO that is active in acute cardiac allograft rejection. Up-regulation of iNOS occurs in macrophage cellular infiltrates and later within the graft parenchymal cells. In human cardiac transplantation a positive correlation has shown between iNOS expression and left ventricular contractile dysfunction measured by echocardiography and Doppler techniques We have recently developed a novel PET radiotracer, [18F](+/-)NOS, designed to measure cellular iNOS activity. This study evaluates the feasibility of the method in OHT patients undergoing surveillance endomyocardial biopsy as part of their normal post-transplant evaluation for potential allograft rejection. More specifically, it will compare the myocardial kinetics of this radiotracer measured by PET with tissue measurements of iNOS measured by immunohistochemistry.

  Eligibility

Ages Eligible for Study:   21 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Sampling Method:   Probability Sample
Study Population

Patients 21 years of age or older of either sex, who are status-post heart transplant and normal healthy volunteers (2 women and 2 men) will be enrolled.

Criteria

Inclusion Criteria:

  1. The OHT patients will be undergoing surveillance endomyocardial biopsy and will Patients 21 years of age or older of either sex, who are status-post OHT and normal healthy volunteers (2 women and 2 men) will be enrolled.be on standard immunosuppressive therapy and anti-hyperlipidemic, anti-hypertensive and anti-diabetic therapies as needed. "Healthy volunteer" is someone who has volunteered to be imaged and who, based on physical exam and baseline electrocardiogram, has no evidence of cardiovascular disease, is not on medication, such as steroids, that will interfere with the accuracy of measuring [18F](+/-)NOS activity and is not under the care of a physician for any active medical conditions.
  2. Able to give informed consent.
  3. Not currently pregnant or nursing: Female subjects must be either: surgically sterile (has had a documented bilateral oophorectomy and/or documented hysterectomy), post menopausal (cessation of menses for more than 1 year), or of childbearing potential for whom a urine pregnancy test (with the test performed within the 24 hour period immediately prior to administration of [18F](+/-)NOS) is negative.

Exclusion Criteria:

  1. Patients with an unstable cardiovascular (e.g., severe rejection) or other clinical condition (e.g., active severe infection) that in the opinion of the Principal Investigator or designee or Dr. Ewald precludes participation in the study.
  2. Unable to tolerate 60-90 mins of PET imaging or is claustrophobic.
  3. Normal volunteers with evidence of cardiovascular disease or other diseases based on clinical evaluation and/or blood laboratory tests, which are judged by the Principal Investigator or designee to interfere with accurate determination of the of [18F](+/-)NOS on such measures.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01066637

Contacts
Contact: Deborah Delano, RN 314-747-3876 delanod@mir.wustl.edu
Contact: Ali A Jamal, MD 314-747-3839 jamala@mir.wustl.edu

Locations
United States, Missouri
Washington University School of Medicine Recruiting
St.Louis, Missouri, United States, 63110
Contact: Deborah Delano, RN    314-747-3876    delanod@mir.wustl.edu   
Contact: Ali A Jamal, MD    314-747-3839    jamala@mir.wustl.edu   
Principal Investigator: Robert J Gropler, MD         
Sponsors and Collaborators
Washington University School of Medicine
Investigators
Principal Investigator: Robert J Gropler, MD Washington University School of Medicine
  More Information

No publications provided

Responsible Party: Dr. Robert Gropler, MD, Washington University-St. Louis School of Medicine
ClinicalTrials.gov Identifier: NCT01066637     History of Changes
Other Study ID Numbers: 09-0986
Study First Received: February 8, 2010
Last Updated: May 11, 2011
Health Authority: United States: Institutional Review Board

Keywords provided by Washington University School of Medicine:
iNOS activity in Heart Transplant patients

Additional relevant MeSH terms:
Nitric Oxide
Bronchodilator Agents
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Pharmacologic Actions
Anti-Asthmatic Agents
Respiratory System Agents
Therapeutic Uses
Free Radical Scavengers
Antioxidants
Molecular Mechanisms of Pharmacological Action
Neurotransmitter Agents
Endothelium-Dependent Relaxing Factors
Vasodilator Agents
Cardiovascular Agents
Protective Agents

ClinicalTrials.gov processed this record on April 16, 2014