iNOS With Positron Emission Tomography (PET) in Cellular Inflammation.

NCT01066637 | Completed Early Phase 1 Results DMC

• 2 other identifiers: 09-0986201106273
• Study Type: interventional
• Target: 26
• Locations: 1 country
• Sites: 1

Brief Summary

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 18F-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 18F-NOS may be a useful tool for detecting the early stages of these diseases. The safety of 18F-NOS during the study will also be assessed. All PET imaging will be performed with a CTI/Siemens Biograph 40 PET/CT scanner. Protocol was revised to add new imaging modality, Biograph mMR PET-MR scanner in order to investigate new hardware and software in order to optimize scanning procedures in order to refine image quality so that we can apply the findings to future standard clinical scans and research imaging studies. Ten additional status-post OHT patients who are scheduled for standard of care endomyocardial biopsy for allograft rejection surveillance will undergo PET/MR imaging with \[18F\](+/-)NOS.

Conditions

Patients With Post Orthotopic Heart Transplantation Status

Keywords

Heart transplant patients

Outcome Measures

Primary Outcomes (1)

• To Measure Free Fatty Acid by Imaging Patients With Increased Levels of iNOS Using [18F](+/-)NOS.

  24-72 hours post [18F](+/-)NOS injection

Secondary Outcomes (1)

• To Determine Human Dosimetry in Both Normal Adult Healthy Volunteers and Heart Transplant Patients.

  24-72 hours post [18F](+/-)NOS injection

Study Arms (2)

Dosimetry Group

EXPERIMENTAL

To determine its potential for use in humans, we measured 18F-NOS myocardial activity in patients after orthotopic heart transplantation (OHT) (3 women and 9 men) and normal healthy volunteers (2 women and 2 men), and correlated it with pathologic allograft rejection, tissue iNOS levels, and calculated human radiation dosimetry.

Drug: [18F](+/-)NOS

Kinetic Analysis Group

EXPERIMENTAL

Measurement of myocardial levels of enzyme nitric oxide synthase(iNOS) using PET and 18F-NOS in post heart transplant patients (5 women and 5 men) undergoing endomyocardial biopsy as part of their normal post-transplant evaluation. Kinetic data of the tracer will be compared with the heart tissue measurements of iNOS measured by immunohistochemistry.

Drug: [18F](+/-)NOS

Interventions

[18F](+/-)NOS DRUG

Injection of radiotracer \[18F\](+/-)NOS for PET imaging and kinetic data analysis

Also known as: 6-(1/2)(2-18F-fluoropropyl)-4-methylpyridin-2-amine

Dosimetry Group; Kinetic Analysis Group

Eligibility Criteria

• Age: 21 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• Able to give informed consent.
• 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.

You may not qualify if:

• 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.
• Unable to tolerate 60-90 mins of PET imaging or is claustrophobic.
• 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.

Sponsors & Collaborators

• Washington University School of Medicine: lead

Study Sites (1)

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Related Publications (4)

• Marletta MA. Nitric oxide synthase structure and mechanism. J Biol Chem. 1993 Jun 15;268(17):12231-4. No abstract available.

  PMID: 7685338 BACKGROUND

• Kaneki M, Shimizu N, Yamada D, Chang K. Nitrosative stress and pathogenesis of insulin resistance. Antioxid Redox Signal. 2007 Mar;9(3):319-29. doi: 10.1089/ars.2006.1464.

  PMID: 17184170 BACKGROUND

• Alderton WK, Cooper CE, Knowles RG. Nitric oxide synthases: structure, function and inhibition. Biochem J. 2001 Aug 1;357(Pt 3):593-615. doi: 10.1042/0264-6021:3570593.

  PMID: 11463332 RESULT

• Mollace V, Muscoli C, Masini E, Cuzzocrea S, Salvemini D. Modulation of prostaglandin biosynthesis by nitric oxide and nitric oxide donors. Pharmacol Rev. 2005 Jun;57(2):217-52. doi: 10.1124/pr.57.2.1.

  PMID: 15914468 RESULT

MeSH Terms

Interventions

Fluorine-18

Limitations and Caveats

there were no limitations or caveats

Results Point of Contact

• Title: Robert Gropler, MD, Chief of Cardiovascular Imaging Laboratory
• Organization: Washington University School of Medicine

groplerr@mir.wustl.edu

314-747-3877

Study Officials

• Robert J Gropler, MD

  Washington University School of Medicine

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 8, 2010
• First Posted: February 10, 2010
• Study Start: September 1, 2009
• Primary Completion: June 1, 2012
• Study Completion: June 1, 2012
• Last Updated: August 7, 2020
• Results First Posted: August 7, 2020

Record last verified: 2020-07

Locations

US (1)