FDG-PET Imaging in Young Cystic Fibrosis Patients

The purpose of this research is to determine how a person's lungs will uptake [18F]fluorodeoxyglucose (FDG), as measured with positron emission tomography (PET) scanning in young cystic fibrosis (CF) patients.

Study Overview

• Status: Completed
• Conditions: Cystic Fibrosis
• Intervention / Treatment: Diagnostic test: FDG-PET

Detailed Description

Our recent study in CF adults, supplemented by recent pre-clinical and clinical studies by our group suggests that labeled fluorodeoxyglocose-based positron emission tomography (FDG-PET) imaging may be a valuable quantitative biomarker of lung inflammation. The proposed study would validate our earlier findings, but in a younger patient population. The implications of such a test could be highly significant for both the testing of promising new anti-inflammatory agents and for patient management decisions. To capitalize on this exciting opportunity, the critical next step is to show that we can identify a cohort of young CF patients with both stable lung function and normal (or near normal) FDG-PET imaging studies. Similar patients, then, would become the subjects for a future prospective cohort study to determine if FDG-PET imaging can in fact serve as a predictor of future changes in lung function.

• Study Type: Interventional
• Enrollment (Actual): 21
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Washington University School of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 12 years to 21 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Confirmed diagnosis of cystic fibrosis
• Age 12 to 21 years old, of either gender, any race or ethnicity
• Stable recent pulmonary status (defined as no new pulmonary symptoms, new antibiotic use, or hospitalization for pulmonary symptoms for at least 1 month).
• We will permit patients treated with the macrolide antibiotic, azithromycin, to participate in this study. Azithromycin has recently become a virtual standard of care in CF, based on small but reproducible improvements in pulmonary function over 4 months of treatment with this drug. The mechanism of benefit is uncertain, but an anti-inflammatory effect has been suggested. The high prevalence of use means that a study without azithromycin would likely require a wash-out period, without data about the appropriate duration for such a wash-out, or whether inflammatory markers would reverse during that time.

Exclusion Criteria:

• Failure to obtain informed consent
• Positive pregnancy test or lactation
• Currently enrolled in another study involving radioisotopes or an investigational drug
• Recent (within 30 days of screening) hospitalization for any reason
• New antibiotic use (within 30 days of screening).
• Patient incapable of lying still and supine within the PET/computed X-ray tomography (CT) scanner for 90 minutes.
• Patient incapable of completing other testing procedures (e.g., PFT, induced sputum)
• Patient with serum glucose greater than 150 mg/dl at time of PET imaging study
• Patient incapable of fasting for 4 to 6 hrs prior to PET imaging study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Stable lung function; * Group S (n = 14) will consist of CF patients, aged 12-21 years old, who underwent FDG-PET with stable lung function during the past 4 years, defined as less than 2% decline per year. There is no therapeutic intervention and FDG-PET scan will be performed in both cohorts.	Diagnostic test: FDG-PET; All subjects underwent FDG-PET and low-dose volumetric CT imaging. After completing a transmission scan, [18F]FDG was injected intravenously at the start of dynamic scan acquisition. Regions of interest were drawn over multiple tomographic slices to determine average whole-lung and regional lung tissue [18F] FDG uptake. Patlak graphical analysis was used to determine the rate of [18F]FDG uptake from the blood input function and lung tissue activity curves, measured as the influx constant Ki (slope of the linear regression from the Patlak plot). Corrected Ki (i.e., Ki divided by the initial volume of distribution). Lung density was calculated from the attenuation image by standard methods.
Other: Rapidly deteriorating lung function; * Group R (n = 14) will contain CF patients, aged 12-21 years old, who underwent FDG-PET with rapidly deteriorating lung function during the past 4 years with greater than 4% per year decline. There is no therapeutic intervention and FDG-PET scan will be performed in both cohorts.	Diagnostic test: FDG-PET; All subjects underwent FDG-PET and low-dose volumetric CT imaging. After completing a transmission scan, [18F]FDG was injected intravenously at the start of dynamic scan acquisition. Regions of interest were drawn over multiple tomographic slices to determine average whole-lung and regional lung tissue [18F] FDG uptake. Patlak graphical analysis was used to determine the rate of [18F]FDG uptake from the blood input function and lung tissue activity curves, measured as the influx constant Ki (slope of the linear regression from the Patlak plot). Corrected Ki (i.e., Ki divided by the initial volume of distribution). Lung density was calculated from the attenuation image by standard methods.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Kinetic Influx Constant (Ki)	The whole lung kinetic influx constant (Ki) is the primary outcome measure that is derived from the time-activity curves, which are generated from regions of interest placed over the whole lungs. Therefore, a single time-activity curves from each scan is used to derive the Ki.	At the time of FDG scan, 1 to 2 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Sputum Neutrophil Elastase (NE) Concentration	Using established techniques, functional activity of neutrophil elastase in sputum sols were measured using methoxy-succinyl-ala-ala-pro-val-nitroanilide (Elastin Products, Owensville, MO), specific peptide chromogenic substrates of the neutrophil protease	Sample collected within 2-hours of PET scan

Collaborators and Investigators

• Sponsor: Washington University School of Medicine
• Collaborators: Cystic Fibrosis Foundation
• Investigators: Principal Investigator: Thomas Ferkol, MD, Washington University School of Medicine

Study record dates

Study Major Dates

• Study Start (Actual): February 1, 2009
• Primary Completion (Actual): February 1, 2012
• Study Completion (Actual): February 1, 2012

Study Registration Dates

• First Submitted: February 16, 2009
• First Submitted That Met QC Criteria: February 17, 2009
• First Posted (Estimate): February 18, 2009

Study Record Updates

• Last Update Posted (Actual): July 24, 2018
• Last Update Submitted That Met QC Criteria: June 27, 2018
• Last Verified: June 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Respiratory Tract Diseases; Lung Diseases; Infant, Newborn, Diseases; Genetic Diseases, Inborn; Pancreatic Diseases; Fibrosis; Cystic Fibrosis
• Other Study ID Numbers: 08-1219

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Data generated will be published at the end of the project, consistent with normal scientific practices. Such research data will be anonymized to prevent the disclosure of personal identifiers. In return for the use of data, investigators will acknowledge our grant number in publications and presentations, and in productivity reports on publications or funding that were derived from the project, and they will not distribute materials to third-parties without notification. There will be no charge for sharing data unless the request requires effort beyond what can be subsumed under normal project budgeted effort. If the request justifies a charge, the cost is kept to a minimum and based on actual expenses.
• IPD Sharing Time Frame: Research data will be made available after the main findings from the final research data set have been accepted for publication. The data will be available indefinitely thereafter.
• IPD Sharing Access Criteria: Data may be shared with collaborators as approved by the Principal Investigator based on the following criteria: scientific merit, feasibility and IRB issues, appropriateness of principal investigator qualifications, and appropriateness to the project's overall goals and themes. Approval of the relevant co-investigators will be also sought and reviewed by the principal investigators.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes