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PET Assessment of Acute Lung Transplant Rejection

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ClinicalTrials.gov Identifier: NCT02204202
Recruitment Status : Recruiting
First Posted : July 30, 2014
Last Update Posted : November 3, 2016
Sponsor:
Collaborator:
National Heart, Lung, and Blood Institute (NHLBI)
Information provided by (Responsible Party):
Washington University School of Medicine

Brief Summary:
The purpose of this research study is to gain understanding of the basic responses of the lungs to inflammation and specifically if there may be a better way to detect graft inflammation using non-invasive methods as well as to determine the effectiveness of immunosuppressive treatment regimens in preventing acute rejection in lung transplant recipients.

Condition or disease Intervention/treatment
Lung Disease Drug: [18F]FDG Drug: [18F]ISO-1

Detailed Description:

Positron emission tomography with fluorodeoxyglucose (FDG-PET) is a potential way we can measure lung inflammation. FDG-PET imaging is a clinically accepted and FDA-approved method that is commonly used in the diagnosis and management of cancer. PET is a machine that detects radiation and generates pictures using a donut shaped scanner similar in appearance to an x-ray "CAT" or computed tomography (CT) scan. FDG stands for [18F] fluorodeoxyglucose, a radiolabeled sugar that is used to identify areas of inflammation with the PET scanner. A CT scan takes a picture of what the lungs and airways look like.

T cells are the primary cause of acute rejection of lung transplants. Because T cells must divide in order to be activated and cause rejection, imaging them while they are dividing is another way that we can determine whether acute rejection is occurring. A new PET tracer called [18F]ISO-1 binds to dividing cells. Therefore, [18F]ISO-1 may help us measure acute rejection more accurately. [18F]ISO-1 is an investigational drug.


Study Type : Observational
Estimated Enrollment : 60 participants
Observational Model: Cohort
Time Perspective: Cross-Sectional
Official Title: Positron Emission Tomography Assessment of Acute Lung Transplant Rejection
Study Start Date : February 2014
Estimated Primary Completion Date : January 2018
Estimated Study Completion Date : January 2018

Resource links provided by the National Library of Medicine


Group/Cohort Intervention/treatment
Grade A0
Double-lung transplant recipients with no evidence of rejection who undergo both [18F]FDG and [18F]ISO-1 PET imaging scans
Drug: [18F]FDG
10 millicuries (mCi) of [18F]FDG will be injected intravenously at the start of a 60-minute dynamic PET scan acquisition
Other Name: fluorodeoxyglucose

Drug: [18F]ISO-1
8 mCi of [18F]ISO-1 will be injected intravenously at the start of a 60-minute dynamic PET scan acquisition
Other Name: F-18 labeled proliferation tracer targeting PGRMC1

Grades A2-3
Double-lung transplant recipients with mild to moderate rejection who undergo both [18F]FDG and [18F]ISO-1 PET imaging scans
Drug: [18F]FDG
10 millicuries (mCi) of [18F]FDG will be injected intravenously at the start of a 60-minute dynamic PET scan acquisition
Other Name: fluorodeoxyglucose

Drug: [18F]ISO-1
8 mCi of [18F]ISO-1 will be injected intravenously at the start of a 60-minute dynamic PET scan acquisition
Other Name: F-18 labeled proliferation tracer targeting PGRMC1




Primary Outcome Measures :
  1. Ki, the influx constant that describes the rate of [18F]FDG uptake, in the whole lung [ Time Frame: This outcome measure is assessed from the [18F]FDG scan performed on Day 1. ]
  2. Logan plot analysis determined distribution volume ratio (DVR) of [18F] ISO-1 uptake [ Time Frame: This outcome measure is assessed from the [18F]ISO-1 PET scan performed on Day 2. ]

Secondary Outcome Measures :
  1. Progesterone receptor membrane component 1 (PGRMC1) staining of biopsy tissues and bronchoalveolar lavage cells [ Time Frame: Assessed after the baseline clinical bronchoscopy procedure is performed 3 days prior to FDG PET/CT scan ]
    The biopsy specimens will be stained for proliferation markers. The bronchoalveolar lavage cells will be assessed for glucose uptake with 2-NBDG.


Biospecimen Retention:   Samples Without DNA
cells from bronchoalveolar lavage specimen; tissues from biopsy specimens


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Ages Eligible for Study:   19 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population
Any patient within 7 months of double-lung transplantation and who is scheduled for bronchoscopy with biopsy will be eligible. Patients will be identified via the bronchoscopy schedule through the Lung Transplant Center at Barnes-Jewish Hospital / Washington University School of Medicine and approached for potential participation prior to their scheduled bronchoscopy. PET/CT imaging with [18F]FDG will be performed, if consented, no more than 3 days after results from the biopsy are reported. [18F]ISO-1 PET/CT imaging will be performed the day after [18F]FDG PET and can be performed after treatment for acute rejection has been initiated. We intend to image 30 lung transplant recipients with no evidence of rejection (grade A0) and 30 recipients with mild to moderate (grades A2-3) rejection.
Criteria

Inclusion Criteria:

  • Double-lung transplant recipient
  • Scheduled for bronchoscopy with transbronchial biopsy
  • Capable of lying still and supine with arms raised above the head within the PET/CT scanner for ~1.25 hours
  • Capable of following instructions for breathing protocol during CT portion of PET/CT
  • Able and willing to give informed consent
  • BMI < 35
  • Already scheduled to undergo bronchoscopy with bronchoalveolar lavage (BAL) for clinical reasons
  • Willing to donate a portion of BAL and biopsy specimen for laboratory testing

Exclusion Criteria:

  • Glucose level > 150 mg/dl at time of [18F]FDG PET scan (however, up to 160 mg/dl, with repeat testing showing level is stable or decreasing, is acceptable)
  • Pregnancy (confirmed by qualitative urine human chorionic gonadotropin (hCG) pregnancy test)
  • Lactation
  • Presence of implanted electronic medical device
  • Enrollment in another research study of an investigational drug
  • Inability to lie flat with arms raised above the head for 1.5 hours for PET/CT scans or follow breathing protocol instructions for the CT portion of the PET/CT

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 ClinicalTrials.gov identifier (NCT number): NCT02204202


Contacts
Contact: Delphine L Chen, MD 314-362-7029 chend@mir.wustl.edu
Contact: Debra Kemp, RN, BSN, CRC 314-362-3839 kempd@wusm.wustl.edu

Locations
United States, Missouri
Washington University School of Medicine / Barnes-Jewish Hospital Recruiting
St. Louis, Missouri, United States, 63110
Contact: Delphine L Chen, MD    314-362-7029    chend@mir.wustl.edu   
Principal Investigator: Delphine L Chen, MD         
Sponsors and Collaborators
Washington University School of Medicine
National Heart, Lung, and Blood Institute (NHLBI)
Investigators
Principal Investigator: Delphine L Chen, MD Washington University School of Medicine

Responsible Party: Washington University School of Medicine
ClinicalTrials.gov Identifier: NCT02204202     History of Changes
Other Study ID Numbers: 1R01HL121218-01 ( U.S. NIH Grant/Contract )
R01HL121218 ( U.S. NIH Grant/Contract )
First Posted: July 30, 2014    Key Record Dates
Last Update Posted: November 3, 2016
Last Verified: November 2016

Keywords provided by Washington University School of Medicine:
acute lung transplant rejection
neutrophilic lung inflammation
positron emission tomography imaging
[18F] fluorodeoxyglucose
[18F] ISO-1

Additional relevant MeSH terms:
Lung Diseases
Respiratory Tract Diseases
Fluorodeoxyglucose F18
Radiopharmaceuticals
Molecular Mechanisms of Pharmacological Action