Cystic Fibrosis
Conditions
Brief summary
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.
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.
Interventions
DIAGNOSTIC_TESTFDG-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.
Sponsors
Cystic Fibrosis Foundation
Washington University School of Medicine
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
DIAGNOSTIC
Masking
NONE
Intervention model description
In this pilot study, we examined the value of FDG-PET scans as a noninvasive measure of neutrophilic inflammation in adolescents and young adults with cystic fibrosis. All subjects underwent scans.
Eligibility
Sex/Gender
ALL
Age
12 Years to 21 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Kinetic Influx Constant (Ki) | At the time of FDG scan, 1 to 2 hours | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Sputum Neutrophil Elastase (NE) Concentration | Sample collected within 2-hours of PET scan | 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 |
Countries
United States
Participant flow
Recruitment details
January 2009-December 2012, St. Louis Children's Hospital Cystic Fibrosis Clinics (St. Louis)
Participants by arm
| Arm | Count |
|---|---|
| Stable Lung Function Group S (n = 14) will consist of CF patients, aged 12-21 years old, with stable lung function during the past 4 years, defined as less than 2% decline per year. | 10 |
| Rapidly Declining Lung Function Group R (n = 14) will contain CF patients, aged 12-21 years old, with rapidly deteriorating lung function during the past 4 years with greater than 4% per year decline, as defined in our previous study. | 8 |
| Total | 18 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Physician Decision | 3 | 0 |
Baseline characteristics
| Characteristic | Rapidly Declining Lung Function | Stable Lung Function | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 7 Participants | 8 Participants | 15 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 1 Participants | 2 Participants | 3 Participants |
| Age, Continuous | 16.6 years STANDARD_DEVIATION 2.9 | 15 years STANDARD_DEVIATION 1.9 | 15.5 years STANDARD_DEVIATION 2.6 |
| Region of Enrollment United States | 8 participants | 10 participants | 18 participants |
| Sex: Female, Male Female | 4 Participants | 6 Participants | 10 Participants |
| Sex: Female, Male Male | 4 Participants | 4 Participants | 8 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 10 | 0 / 8 |
| other Total, other adverse events | 0 / 10 | 0 / 8 |
| serious Total, serious adverse events | 0 / 10 | 0 / 8 |
Outcome results
Primary
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.
Time frame: At the time of FDG scan, 1 to 2 hours
Population: CF adolescents and young adults, ages 12 to 21 years, who did not have CFRD.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Stable Lung Function | Kinetic Influx Constant (Ki) | 0.009 mL/min/mL | Standard Deviation 0.008 |
| Rapidly Declining Lung Function | Kinetic Influx Constant (Ki) | 0.013 mL/min/mL | Standard Deviation 0.008 |
Secondary
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
Time frame: Sample collected within 2-hours of PET scan
Population: Not every participant in the stable lung function group could produce sputum.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Stable Lung Function | Sputum Neutrophil Elastase (NE) Concentration | 2179 microgram (mcg) NE /mcg protein | Standard Deviation 2046 |
| Rapidly Declining Lung Function | Sputum Neutrophil Elastase (NE) Concentration | 1656 microgram (mcg) NE /mcg protein | Standard Deviation 926 |