PET Assessment of Acute Lung Transplant Rejection

Lung Disease Clinical Trial

Official title:

Positron Emission Tomography Assessment of Acute Lung Transplant Rejection

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02204202
• Other study ID #: 1R01HL121218-01-201102155
• Secondary ID: R01HL121218
• Status: Terminated
• Start date: February 2014
• Est. completion date: February 4, 2017

Study information

• Verified date: October 2020
• Source: Washington University School of Medicine
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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" computerized axial tomography or computed tomography (CT) scan. FDG stands for [18F] (flourine 18) 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 (18F-labeled σ2-receptor ligand for PET, N-(4-(6,7-dimethoxy-3,-4-dihydroisoquinolin-2(1H)-yl)butyl)-2-(2-18F-fluoroethoxy)-5-methylbe nzamide (18F-3c), binds to dividing cells. Therefore, [18F]ISO-1 may help us measure acute rejection more accurately. [18F]ISO-1 is an investigational drug.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 28
• Est. completion date: February 4, 2017
• Est. primary completion date: February 4, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 19 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Lung Disease
• Lung Diseases

Intervention

Drug:
• [18F]FDG
10 millicuries (mCi) of [18F]FDG will be injected intravenously at the start of a 60-minute dynamic PET scan acquisition
• [18F]ISO-1
8 mCi of [18F]ISO-1 will be injected intravenously at the start of a 60-minute dynamic PET scan acquisition

Locations

Country	Name	City	State
United States	Washington University School of Medicine / Barnes-Jewish Hospital	Saint Louis	Missouri

Sponsors (2)

Lead Sponsor	Collaborator
Washington University School of Medicine	National Heart, Lung, and Blood Institute (NHLBI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Ki, the influx constant that describes the rate of [18F]FDG uptake, in the whole lung		This outcome measure is assessed from the [18F]FDG scan performed on Day 1.
Primary	Logan plot analysis determined distribution volume ratio (DVR) of [18F] ISO-1 uptake		This outcome measure is assessed from the [18F]ISO-1 PET scan performed on Day 2.
Secondary	Progesterone receptor membrane component 1 (PGRMC1) staining of biopsy tissues and bronchoalveolar lavage cells	The biopsy specimens will be stained for proliferation markers. The bronchoalveolar lavage cells will be assessed for glucose uptake with 2-NBDG ( fluorescent glucose analog that has been used to monitor glucose uptake in live cells, as an indicator of cell viability).	Assessed after the baseline clinical bronchoscopy procedure is performed 3 days prior to FDG PET/CT scan