Exploration of Metabolome in Patients With Interstitial Lung Disease and Pulmonary Hypertension With or Without Specific Pulmonary Hypertension Treatment (BREATH-TPT)

Blood and uRine Metabolomics Exploration for Assessing Thoracic Health After Treatment of Group 3 Pulmonary Hypertension

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.

Study Overview

• Status: Recruiting
• Conditions: Interstitial Lung Disease; Precapillar Pulmonary Hypertension
• Intervention / Treatment: Other: Blood sampling for metabolomic profiling; Other: Urine sampling for metabolomic profiling

• Study Type: Observational
• Enrollment (Estimated): 80

Contacts and Locations

• Study Contact: Name: Ségolène TURQUIER; Phone Number: +33 04 72 35 73 32; Email: segolene.turquier@chu-lyon.fr
• Study Contact Backup: Name: David LAVILLE; Phone Number: +33 04 27 85 51 39; Email: david.laville@etu.univ-lyon1.fr

Study Locations

• France
  • Rhone
    • Bron, Rhone, France, 69500
      • Recruiting
      • Hôpital Cardiologique et Pneumologique Louis Pradel
      • Contact: Ségolène TURQUIER; Phone Number: +33 04 72 35 73 32; Email: segolene.turquier@chu-lyon.fr
      • Contact: David LAVILLE; Phone Number: +33 04 27 85 51 39; Email: david.laville@chu-lyon.fr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

• Sampling Method: Non-Probability Sample

Study Population

Adult patients monitored at Hospices Civils de Lyon for Interstitial Lung Disease, with suspected group 3 PH, for whom the medical team is considering or discussing the indication for specific ILD-PH treatment.

Description

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

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Group "intervention"; Patients who suffer from ILD and ILD-PH from this group will be given specific treatments (especially inhaled TREPROSTINIL, up to 3 breath per use; 4 uses a day) for ILD-PH after usual independent collegial consultation Those patients will have before and after treatment blood and urine metabolomic profile. They will have baseline and follow up blood and urine sampling. They will be offer possibility to perform up to 6 auto-sampling at home.	Other: Blood 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); Other: Urine 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).
Group " control "; Patients who suffer from ILD and ILD-PH from this group will not be given specific ILD-PH treatment based on insufficient haemodynamic data or clinical contraindications after independent collegial consultation. They will have only baseline blood and urine sampling.	Other: Blood 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); Other: Urine 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).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Comparison of urinary metabolite concentrations before and after initiation of treatment measured centrally by proton nuclear magnetic resonance spectroscopy (¹H-NMR).	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	Outcome is measured when all patients will have their 4-6 months follow-up completed.
Comparison of blood metabolite concentrations before and after initiation of treatment measured centrally by proton nuclear magnetic resonance spectroscopy (¹H-NMR).	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	Outcome is measured when all patients will have their 4-6 months follow-up completed.
Comparative prognosis analysis within sub-groups	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.	Outcome is measured when all patients will have their 4-6 months follow-up completed.

Collaborators and Investigators

• Sponsor: Hospices Civils de Lyon

Study record dates

Study Major Dates

• Study Start (Actual): February 16, 2026
• Primary Completion (Estimated): August 16, 2029
• Study Completion (Estimated): August 16, 2029

Study Registration Dates

• First Submitted: November 19, 2025
• First Submitted That Met QC Criteria: November 19, 2025
• First Posted (Actual): November 28, 2025

Study Record Updates

• Last Update Posted (Actual): February 17, 2026
• Last Update Submitted That Met QC Criteria: February 16, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Keywords: Metabolomic; Inhaled Treprostinil; ILD-PH; PH treatment
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Lung Diseases; Lung Diseases, Interstitial; Investigative Techniques; Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Punctures; Surgical Procedures, Operative; Blood Specimen Collection
• Other Study ID Numbers: 69HCL25_0216

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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