Fibroblast Growth Factor 23 in Chronic Respiratory Failure

Chronic Respiratory Failure Clinical Trial

— EFIC-RES  

Official title:

"Exploration of the Role of Intact Fibroblast Growth Factor 23 and Its C-terminal Fragment in Chronic Respiratory Failure "

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT05258370
• Other study ID #: APHP201305
• Secondary ID: 2020-A02607-32
• Status: Not yet recruiting
• Start date: June 2023
• Est. completion date: May 2026

Study information

• Verified date: April 2023
• Source: Assistance Publique - Hôpitaux de Paris
• Contact: Natacha Nohilé
• Phone: 331 56 09 59 82
• Email: natacha.nohile[@]aphp.fr
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 50
• Est. completion date: May 2026
• Est. primary completion date: May 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Chronic Respiratory Failure
• Respiratory Insufficiency

Intervention

Other:
• Dosage
Evaluation of circulating C-terminal FGF23 (FGF23Ct) rate, circulating intact FGF23 (FGF23i) rate and Erythropoietin
• Cardiac echography
12 months after patient enrollment

Locations

Country	Name	City	State
n/a

Sponsors (2)

Lead Sponsor	Collaborator
Assistance Publique - Hôpitaux de Paris	Fondation Université de Paris

References & Publications (4)

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	circulating C-terminal FGF23 (FGF23Ct)	ELISA method	at inclusion (before oxygen therapy)
Primary	circulating intact FGF23 (FGF23i)	ELISA method	at inclusion (before oxygen therapy)
Secondary	circulating FGF23Ct	ELISA method	at month 3 and month 12
Secondary	circulating FGF23i	ELISA method	at month 3 and month 12
Secondary	circulating erythropoietin	ELISA method	at inclusion, month 3 and month 12
Secondary	arterial O2 saturation	assessed using an arterial sampling	at inclusion, month 3 (without and with 02 therapy) and month 12 (without and with 02 therapy)
Secondary	PaO2 (arterial partial oxygen pressure)	assessed using an arterial sampling	at inclusion, month 3 (without and with 02 therapy) and month 12 (without and with 02 therapy)
Secondary	Assessment of systolic function	left ventricular ejection fraction assessed using cardiac ultrasound	at inclusion and month 12
Secondary	left ventricular mass indexed for body surface area	using cardiac ultrasound	at inclusion and month 12
Secondary	Assessment of diastolic function	Recording of mitral filling flow using cardiac ultrasound	at inclusion and month 12
Secondary	Assessment of pulmonary artery pressure	with measure, using cardiac ultrasound, of; The Vmax of the tricuspid insufficiency flow which gives the systolic gradient right heart ventricle/right heart atrium; And the diameter the inferior vena cava	at inclusion and month 12