- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03692481
Evolution of Lung 18FDG Uptake in Patients With Idiopathic Pulmonary Fibrosis and Receiving Pirfenidone (PET-Fibrosis)
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
Idiopathic pulmonary fibrosis (IPF) is a rare and fatal lung disease characterized by an unpredictable evolution with variable kinetics of progression and burdened by the occurrence of exacerbation. The evaluation of the prognosis in a given patient remains difficult. Impaired lung function assessed by the value of forced vital capacity (FVC) and diffusion of lung carbon monoxide (DLCO) at the time of diagnosis, or decline in lung function within 6 or 12 months after the diagnosis, are the best predictive markers of survival but fail to assess or to predict lung function decline. Until recently, lung transplantation was the only IPF treatment and remains associated with high morbidity and mortality. Pirfenidone and nintedanib - anti-fibrotic treatments - are now validated therapies in the management of mild-to-moderate IPF defined by FVC ≥ 50% of predictive value and by DLCO ≥ 30 % of predicted value. Several international clinical trials demonstrated that pirfenidone and nintedanib significantly reduce the lung function decline and the exacerbations incidence and significantly improve survival. The emergence of these innovative but costly therapies - which are associated with a non-negligible rate of adverse effects - requires the development of tools to evaluate their effectiveness and monitor anti-fibrotic activity. The 18-fluorodesoxyglucose (18FDG) lung uptake may be the first tool to predict early therapeutic response. PET offers the possibility to quantify in vivo and non-invasively the cell metabolism, using a non-metabolizable substrate labeled as 18FDG. Several parameters can be measured in an automated and reproducible manner such as the mean uptake intensity (SUV mean), the maximum uptake intensity (SUV max), the metabolic lung volume measurement (MLV) or finally the measurement of tissue glycolytic activity or TLG (total lesion glycolysis). 18FDG PET scanner plays a key role in the diagnosis and monitoring of neoplasia and inflammatory diseases such as sarcoidosis. Recent studies reported a change of the metabolic activity of pulmonary fibroblasts issued from IPF, showing increase of glycolytic activity. In a recent study, the investigators demonstrated a strong correlation between the lung uptake parameters and the lung function tests results and prognostic score GAP. In addition, MLV and TLG were prognostic and independently associated with progression-free survival at 12 months. Preliminary data suggest that the intensity of lung 18FDG uptake may be a prognostic marker but also a predictive marker of response to anti-fibrotic treatments. A prospective study must be conducted to confirm or refute these observations.
Primary objective: The main objective of this study is to describe the changes of 18FDG lung uptake assessed by TLG variation in patients with IPF, 12 weeks after the initiation of pirfenidone.
Secondary objectives: Secondary objectives include the following : 1. To describe the changes of 18FDG lung uptake assessed by other 18FDG indices (SUVmean, SUVmax and MLV) in patients with IPF, 12 weeks after the initiation of pirfenidone ; 2. To study the relationship between the variation of 18FDG lung uptake 12 weeks after the initiation of pirfenidone therapy (as assessed by the changes of TLG, SUVmean, SUVmax and MLV) and the decline of FVC 12, 24, 36 and 48 weeks after the initiation of pirfenidone therapy ; 3. To estimate the predictive performance of the variation of 18FDG lung uptake 12 weeks after the beginning of pirfenidone therapy for therapeutic efficacy at 24 weeks.
Experimental plan: This is an interventional, prospective, multicenter, proof of concept study. 18FDG PET-scanner will be performed at baseline and 12 weeks after the beginning of pirfenidone treatment in each patient. Lung Function Tests will be also performed before and 12 weeks after initiation of pirfenidone treatment and will be repeated every 12 weeks until 48 weeks after pirfenidone initiation. A clinical examination and liver enzymes will be assessed every 12 weeks. The occurrence of any adverse event will be collected throughout the trial. LFTs will be interpreted blindly from the results of 18FDG uptake.
Study Type
Enrollment (Anticipated)
Phase
- Not Applicable
Contacts and Locations
Study Contact
- Name: Bruno Crestani, MD, PhD
- Phone Number: 00 33 1 40 25 68 00
- Email: bruno.crestani@aphp.fr
Study Locations
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-
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Paris, France, 75018
- Recruiting
- Service de Pneumologie A Centre constitutif de référence des maladies pulmonaires rares Hôpital Bichat Claude Bernard
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Contact:
- Bruno Crestani, MD, PhD
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-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- IPF, diagnosed accordingly to ATS/ERS/JRS/ALAT international guidelines
- FVC≥50% and DLCO≥30%
- Decision to initiate a treatment with pirfenidone
- Affiliation to the French social security system
Exclusion Criteria:
Will be non-eligible in this study any patient:
- with an age lower than 18 years
- with a life expectancy lower than 12 months as assessed by the investigator
- taking an anti-fibrotic treatment (pirfenidone, nintedanib or any experimental molecule) in the previous three months
- treated by corticosteroid therapy (daily dose > 10 mg, prednisone equivalent)
- with neoplasia localized in thorax
- with contraindication to pirfenidone according to the French Summary of Product Characteristics : hypersensitivity to the active substance or to any of the excipients, past history of angioedema with pirfenidone, concomitant treatment with fluvoxamine, severe or terminal hepatic insufficiency, severe renal insufficiency (CrCl <30ml / min) or end-stage requiring dialysis
- with a positive pregnancy test or currently breastfeeding
- with contraindication to performing a 18FDG PETscan, ie 18FDG hypersensitivity
- with emphysema extension >15% on HRCT according to Cottin et al (16).
Study Plan
How is the study designed?
Design Details
- Primary Purpose: OTHER
- Allocation: NA
- Interventional Model: SINGLE_GROUP
- Masking: NONE
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
EXPERIMENTAL: 18FDG-PET scan
18FDG PET scan will be performed in each patient before initiation of pirfenidone and after 12 weeks of treatment
|
18FDG PET scan will be performed in each patient before initiation of pirfenidone and after 12 weeks of treatment
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Changes of 18FDG lung uptake (TLG variation) in patients with IPF 12 weeks after the initiation of pirfenidone
Time Frame: 12 weeks
|
To describe the changes of 18FDG lung uptake assessed by TLG variation in patients with IPF 12 weeks after the initiation of pirfenidone
|
12 weeks
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Change of 18FDG lung uptake in patients with IPF 12 weeks after the initiation of pirfenidone : variation of SUVmean between baseline and after 12 weeks of treatment
Time Frame: 12 weeks
|
Values of SUVmean will be compared between baseline (treatment initiation with pirfenidone) and the 12 weeks using a Wilcoxon's signed rank test
|
12 weeks
|
Change of 18FDG lung uptake in patients with IPF 12 weeks after the initiation of pirfenidone : variation of SUVmax between baseline and after 12 weeks of treatment
Time Frame: 12 weeks
|
Values of SUVmax will be compared between baseline (treatment initiation with pirfenidone) and the 12 weeks using a Wilcoxon's signed rank test
|
12 weeks
|
Change of 18FDG lung uptake in patients with IPF 12 weeks after the initiation of pirfenidone : variation of MLV between baseline and after 12 weeks of treatment
Time Frame: 12 weeks
|
Values of MLV will be compared between baseline (treatment initiation with pirfenidone) and the 12 weeks using a Wilcoxon's signed rank test
|
12 weeks
|
Variation of the PET parameter SUVmean between baseline and 12 weeks and FVC at 12, 24, 36 and 48 weeks
Time Frame: 48 weeks
|
Relationship between the variation of SUVmean values between baseline and 12 weeks after treatment initiation and the decline of FVC over time will be assessed using a linear mixed effect model of the evolution of FVC over time and the effect of the change of each PET parameter on the decline of FVC over time will be tested
|
48 weeks
|
Variation of the PET parameter SUVmax between baseline and 12 weeks and FVC at 12, 24, 36 and 48 weeks
Time Frame: 48 weeks
|
Relationship between the variation of SUVmax values between baseline and 12 weeks after treatment initiation and the decline of FVC over time will be assessed using a linear mixed effect model of the evolution of FVC over time and the effect of the change of each PET parameter on the decline of FVC over time will be tested
|
48 weeks
|
Variation of the PET parameter TLG between baseline and 12 weeks and FVC at 12, 24, 36 and 48 weeks
Time Frame: 48 weeks
|
Relationship between the variation of TLG values between baseline and 12 weeks after treatment initiation and the decline of FVC over time will be assessed using a linear mixed effect model of the evolution of FVC over time and the effect of the change of each PET parameter on the decline of FVC over time will be tested
|
48 weeks
|
Variation of the PET parameter MLV between baseline and 12 weeks and FVC at 12, 24, 36 and 48 weeks
Time Frame: 48 weeks
|
Relationship between the variation of MLV values between baseline and 12 weeks after treatment initiation and the decline of FVC over time will be assessed using a linear mixed effect model of the evolution of FVC over time and the effect of the change of each PET parameter on the decline of FVC over time will be tested
|
48 weeks
|
Evaluation of the performance of the PET scanner (Sensitivity, Specificity, Positive predictive value and Negative predictive value) using the variation of each PET parameter and the therapeutic response at 24 weeks (succes versus failure)
Time Frame: 24 weeks
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The performance of the PET scanner (Sensitivity, Specificity, Positive predictive value, and Negative predictive value) will be studied using the variation of each PET parameter and the therapeutic response at 24 weeks. A non-parametric Wilcoxon test will be used to compare the variation of each PET parameter according to the therapeutic response. The therapeutic response will be classified as therapeutic failure in the case of any of the following events between pirfenidone treatment initiation and 24 weeks: a relative decline in percent predicted FVC ≥10%, an absolute decline in 6MWT distance ≥50 m, or death from any cause, or as therapeutic success (in any other case). |
24 weeks
|
Collaborators and Investigators
Investigators
- Principal Investigator: Bruno Crestani, MD, PhD, Assistance Publique - Hôpitaux de Paris
Study record dates
Study Major Dates
Study Start (ACTUAL)
Primary Completion (ANTICIPATED)
Study Completion (ANTICIPATED)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (ACTUAL)
Study Record Updates
Last Update Posted (ACTUAL)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- P180301J
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
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