Interstitial Lung Disease, Precapillar Pulmonary Hypertension
Conditions
Keywords
ILD-PH, Inhaled Treprostinil, PH treatment, Metabolomic
Brief summary
Fibrosing interstitial lung diseases (FILDs) encompass a group of rare diseases characterized by progressive pulmonary fibrosis leading to respiratory failure. Current treatments primarily aim to slow disease progression but remain limited, making lung transplantation the ultimate recourse. The development of pulmonary hypertension (PH) in the context of FILDs significantly worsens morbidity and mortality and drastically reduces patients' life expectancy. Conventional treatments for PH are generally ineffective in this setting. Nevertheless, some promising therapeutic agents are currently under investigation, particularly inhaled prostacyclin analogs such as treprostinil, which have demonstrated efficacy in recent clinical studies. Our study aims to explore, in a minimally invasive manner, variations in metabolites in the serum and urine of patients with PH secondary to FILDs, before and during treatment. The main objective is to better understand the systemic effect of these treatments. Furthermore, the identification of metabolomic signatures will allow us to differentiate responders from non-responders, thus providing valuable prognostic and predictive criteria. To date, some patients do not benefit from the available treatments, and better selection of responders could prevent iatrogenic effects in patients whose clinical condition is already fragile. In addition, characterizing the systemic mode of action of these treatments could pave the way for new clinical research focused on the profiles of responding patients. Finally, a thorough understanding of the efficacy of the studied therapies is essential. Indeed, effective treatment of PH in the context of FILDs could not only slow disease progression but also reduce the need for lung transplantation, a major challenge in a context of organ shortage.
Interventions
OTHERBlood sampling for metabolomic profiling
Blood (veinous) will be collected under standard care conditions, in a dry red blood tube without additional gel (4 mL) to obtain serum after centrifugation for 10 minutes at 1500g, in the form of 500µL aliquots, labelled with the patient's code in the study. This sampling will be performed at baseline in both group; and after follow up completion in Group 1 (4-6 month)
OTHERUrine sampling for metabolomic profiling
Urine collected from patient into a dry powder compact in the waiting room before or after the consultation. Preparation of two cryotubes containing at least 1 mL per sample, labelled with the patient's code in the study. In the absence of a calling point, strict aseptic conditions are not required, as the use of chemicals or antiseptic soaps can interfere with the dosages. This sampling will be performed in Group 1 and 2 at baseline; and in Group 1 at 2-month and after completion of follow-up time (4-6 month).
Sponsors
Hospices Civils de Lyon
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
* Patients suffering from progressive interstitial lung disease (ILD) and especially lung fibrosis * Suspicion of precapillar pulmonary hypertension (group 3 PH / ILD-PH) * Patients undergoing cardiac catheterisation for haemodynamic confirmation * Patient who has given informed consent
Exclusion criteria
* Patients suffering from other forms of PH (i.e. PAH, CTEPH, heart failure, multifactorial
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Comparison of urinary metabolite concentrations before and after initiation of treatment measured centrally by proton nuclear magnetic resonance spectroscopy (¹H-NMR). | Outcome is measured when all patients will have their 4-6 months follow-up completed. | The 1H-NMR analysis of each patient's urine will enable us to obtain a table showing the absolute concentration of metabolites per individual. The effects of the drug response will be interpreted following pairwise-comparisons of metabolite concentrations per individual within Group 1, and expressed as fold change to perform a pathway assessment, notably using Metabo Analyst tool |
| Comparison of blood metabolite concentrations before and after initiation of treatment measured centrally by proton nuclear magnetic resonance spectroscopy (¹H-NMR). | Outcome is measured when all patients will have their 4-6 months follow-up completed. | The 1H-NMR analysis of each patient's blood will enable us to obtain a table showing the absolute concentration of metabolites per individual. The effects of the drug response will be interpreted following pairwise-comparisons of metabolite concentrations per individual within Group 1, and expressed as fold change to perform a pathway assessment, notably using Metabo Analyst tool. It will also allow us to explore kidney filtration effect on metabolic profile |
| Comparative prognosis analysis within sub-groups | Outcome is measured when all patients will have their 4-6 months follow-up completed. | Based on clinical response, several subgroups will be defined (responders, non-responders, paradoxical worsening) in order to define prognostic signatures using intergroup statistical comparisons of baseline metabolic concentrations. |
Countries
France
Contacts
CONTACTSégolène TURQUIER
CONTACTDavid LAVILLE
Outcome results
None listed