Fibroblast Growth Factor 23 in Chronic Respiratory Failure

Study Purpose

Fibroblast growth factor 23 (FGF23) is a key hormone of the mineral metabolism produced in bone and acting on the kidney to lower phosphatemia. FGF23 is subject to inactivating proteolytic cleavage which results in the presence of C-terminal and N-terminal fragments heretofore described as inactive. We recently showed an increase in FGF23Ct in sickle cell patients, its association with left ventricular mass as well as a direct, pro-hypertrophic effect of FGF23Ct on rat cardiomyocytes. Data from the literature suggest that hypoxia (linked or not to anemia) is responsible for an increase in the production and cleavage of FGF23, either via the hypoxia inducible factor (HIF1α) or via the increase in erythropoietin (EPO). We hypothesize that the FGF23Ct / FGF23i ratio is increased in response to chronic tissue hypoxia, in the absence of anemia, in patients with chronic respiratory failure (CRF) either due to a direct response to hypoxia via the stimulation of HIF1α, or indirectly via the increase in the circulating concentration of EPO. This elevation, if proven, could contribute to the increased risk of heart disease seen in some populations of CRF. We propose to test this hypothesis by assaying FGF23Ct and FGF23i in a cohort of adult CRF patients before and after initiation of oxygen therapy. The object of the present study is to study the FGF23Ct / FGF23i ratio in incident patients presenting with a non treated CRF as well as the modifications of this ratio under oxygen therapy and to study the correlations between FGF23 Ct and FGF23 and i) oxygen saturation and PaO2 ii) echocardiographic parameters and iii) EPO concentrations. Three visits are planned: Baseline (before initiation of oxygen therapy), and two visits after initiation of oxygen therapy, at 3 months (M3) and at 12 months (M12). For each visit, anthropometric and clinical data, treatment and biological results will be collected. FGF23 intact , FGF23 C-terminal and Erythropoietin will be measured. A cardiac ultrasound will be performed at baseline and at M12.

Recruitment Criteria

Accepts Healthy Volunteers Healthy volunteers are participants who do not have a disease or condition, or related conditions or symptoms	No
Study Type An interventional clinical study is where participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes. An observational clinical study is where participants identified as belonging to study groups are assessed for biomedical or health outcomes. Searching Both is inclusive of interventional and observational studies.	Observational
Eligible Ages	18 Years and Over
Gender	All

More Inclusion & Exclusion Criteria

Inclusion Criteria:

- Patient informed and not opposed to participating in the research.

- Age ≥ 18 years old.

- Severe chronic respiratory failure defined by PaO2 <60 mmHg, whatever the cause, and justifying the initiation of long-term oxygen therapy.

- Not yet treated or with stopping oxygen therapy for at least 6 weeks.

- Be affiliated with a social security scheme or be a beneficiary of such a scheme.

- Be able to understand the interest and the constraints of the study.

Exclusion Criteria:

- Exacerbation of respiratory failure in the 6 weeks prior to inclusion.

- Chronic kidney disease defined by a glomerular filtration rate (GFR) estimated by CKD-EPI <60 mL / min / 1.73m2.

- Anemia at the time of inclusion whatever the cause (sickle cell anemia, thalassemia, hemolytic anemia, chronic iron deficiency, others) - Pregnancy.

- Breastfeeding women.

- Simultaneous participation in another therapeutic trial.

- Patient under guardianship or curatorship.

- Patient under medical help from the French government

Trial Details

Trial ID: This trial id was obtained from ClinicalTrials.gov, a service of the U.S. National Institutes of Health, providing information on publicly and privately supported clinical studies of human participants with locations in all 50 States and in 196 countries.	NCT05258370
Phase Phase 1: Studies that emphasize safety and how the drug is metabolized and excreted in humans. Phase 2: Studies that gather preliminary data on effectiveness (whether the drug works in people who have a certain disease or condition) and additional safety data. Phase 3: Studies that gather more information about safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs. Phase 4: Studies occurring after FDA has approved a drug for marketing, efficacy, or optimal use.
Lead Sponsor The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data.	Assistance Publique - Hôpitaux de Paris
Principal Investigator The person who is responsible for the scientific and technical direction of the entire clinical study.	Marie COURBEBAISSE, MDNicolas ROCHE, MD
Principal Investigator Affiliation	Assistance Publique - Hôpitaux de ParisAssistance Publique - Hôpitaux de Paris
Agency Class Category of organization(s) involved as sponsor (and collaborator) supporting the trial.	Other
Overall Status	Not yet recruiting
Countries
Conditions The disease, disorder, syndrome, illness, or injury that is being studied.	Chronic Respiratory Failure

Arms & Interventions

Arms

: incident patients with chronic respiratory failure

adult patients with untreated chronic respiratory failure

Interventions

Other: - Dosage

Evaluation of circulating C-terminal FGF23 (FGF23Ct) rate, circulating intact FGF23 (FGF23i) rate and Erythropoietin

Other: - Cardiac echography

12 months after patient enrollment

Contact Information

This trial has no sites locations listed at this time. If you are interested in learning more, you can contact the trial's primary contact:

Natacha Nohilé

natacha.nohile@aphp.fr

331 56 09 59 82

For additional contact information, you can also visit the trial on clinicaltrials.gov.

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