Fibroblast Growth Factor 23 in Chronic Respiratory Failure

NCT05258370 | Not Yet Recruiting

• 2 other identifiers: APHP2013052020-A02607-32
• Study Type: observational
• Target: 50
• Locations: 0 countries
• Sites: N/A

Brief Summary

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.

Conditions

Chronic Respiratory Failure

Keywords

fibroblast growth factor 23; erythropoietin; cardiac hypertrophy; pulmonary hypertension; oxygen therapy; chronic respiratory failure

Outcome Measures

Primary Outcomes (2)

• circulating C-terminal FGF23 (FGF23Ct)

  ELISA method

  at inclusion (before oxygen therapy)

• circulating intact FGF23 (FGF23i)

  ELISA method

  at inclusion (before oxygen therapy)

Secondary Outcomes (9)

• circulating FGF23Ct

  at month 3 and month 12

• circulating FGF23i

  at month 3 and month 12

• circulating erythropoietin

  at inclusion, month 3 and month 12

• arterial O2 saturation

  at inclusion, month 3 (without and with 02 therapy) and month 12 (without and with 02 therapy)

• PaO2 (arterial partial oxygen pressure)

  at inclusion, month 3 (without and with 02 therapy) and month 12 (without and with 02 therapy)

Study Arms (1)

incident patients with chronic respiratory failure

adult patients with untreated chronic respiratory failure

Other: Dosage; Other: Cardiac echography

Interventions

Dosage OTHER

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

incident patients with chronic respiratory failure

Cardiac echography OTHER

12 months after patient enrollment

incident patients with chronic respiratory failure

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

adult patients with untreated chronic respiratory Ffilure with an indication to oxygen therapy and free from chronic kidney disease.

You may qualify if:

• 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

You may not qualify if:

• Chronic kidney disease defined by a glomerular filtration rate (GFR) estimated by CKD-EPI \<60 mL / min / 1.73m2
• Pregnancy
• Breastfeeding women
• Simultaneous participation in another therapeutic trial
• Patient under guardianship or curatorship
• Patient under medical help from the French government

Sponsors & Collaborators

• Assistance Publique - Hôpitaux de Paris: lead
• Fondation Université de Paris: collaborator

Related Publications (4)

• Courbebaisse M, Mehel H, Petit-Hoang C, Ribeil JA, Sabbah L, Tuloup-Minguez V, Bergerat D, Arlet JB, Stanislas A, Souberbielle JC, Le Clesiau H, Fischmeister R, Friedlander G, Prie D. Carboxy-terminal fragment of fibroblast growth factor 23 induces heart hypertrophy in sickle cell disease. Haematologica. 2017 Feb;102(2):e33-e35. doi: 10.3324/haematol.2016.150987. Epub 2016 Oct 27. No abstract available.

  PMID: 27789679 BACKGROUND

• Clinkenbeard EL, Hanudel MR, Stayrook KR, Appaiah HN, Farrow EG, Cass TA, Summers LJ, Ip CS, Hum JM, Thomas JC, Ivan M, Richine BM, Chan RJ, Clemens TL, Schipani E, Sabbagh Y, Xu L, Srour EF, Alvarez MB, Kacena MA, Salusky IB, Ganz T, Nemeth E, White KE. Erythropoietin stimulates murine and human fibroblast growth factor-23, revealing novel roles for bone and bone marrow. Haematologica. 2017 Nov;102(11):e427-e430. doi: 10.3324/haematol.2017.167882. Epub 2017 Aug 17. No abstract available.

  PMID: 28818868 BACKGROUND

• Zhang Q, Doucet M, Tomlinson RE, Han X, Quarles LD, Collins MT, Clemens TL. The hypoxia-inducible factor-1alpha activates ectopic production of fibroblast growth factor 23 in tumor-induced osteomalacia. Bone Res. 2016 Jul 5;4:16011. doi: 10.1038/boneres.2016.11. eCollection 2016.

  PMID: 27468359 BACKGROUND

• Faul C, Amaral AP, Oskouei B, Hu MC, Sloan A, Isakova T, Gutierrez OM, Aguillon-Prada R, Lincoln J, Hare JM, Mundel P, Morales A, Scialla J, Fischer M, Soliman EZ, Chen J, Go AS, Rosas SE, Nessel L, Townsend RR, Feldman HI, St John Sutton M, Ojo A, Gadegbeku C, Di Marco GS, Reuter S, Kentrup D, Tiemann K, Brand M, Hill JA, Moe OW, Kuro-O M, Kusek JW, Keane MG, Wolf M. FGF23 induces left ventricular hypertrophy. J Clin Invest. 2011 Nov;121(11):4393-408. doi: 10.1172/JCI46122. Epub 2011 Oct 10.

  PMID: 21985788 BACKGROUND

Biospecimen

Retention: SAMPLES WITHOUT DNA

Plasma, serum

MeSH Terms

Conditions

Cardiomegaly; Hypertension, Pulmonary

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases; Hypertrophy; Pathological Conditions, Anatomical; Pathological Conditions, Signs and Symptoms; Lung Diseases; Respiratory Tract Diseases; Hypertension; Vascular Diseases

Study Officials

• Marie COURBEBAISSE, MD

  Assistance Publique - Hôpitaux de Paris

  STUDY DIRECTOR

• Nicolas ROCHE, MD

  Assistance Publique - Hôpitaux de Paris

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Natacha Nohilé

CONTACT

331 56 09 59 82; natacha.nohile@aphp.fr

Study Design

• Study Type: observational
• Observational Model: CASE ONLY
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 17, 2022
• First Posted: February 28, 2022
• Study Start: June 1, 2023
• Primary Completion: May 1, 2026
• Study Completion: May 1, 2026
• Last Updated: April 18, 2023

Record last verified: 2023-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, ICF
• Time Frame: Two years after the last publication
• Access Criteria: Data sharing must be accepted by the sponsor and the PI based on a scientific project and scientific involvement of the PI team. Collaboration will be fostered. Data sharing must respect the agreements made with funders. Teams wishing obtain IPD must meet the sponsor and IP team to present scientific (and commercial) purpose, IPD needed, format of data transmission, and timeframe. Technical feasibility and financial support will be discussed before mandatory contractual agreement. Processing of shared data must comply with European General Data Protection Regulation (GDPR).