Chronic Respiratory FailureEFIC-RESNCT05258370
Fibroblast Growth Factor 23 in Chronic Respiratory Failure
An observational study of Chronic Respiratory Failure, run by Assistance Publique - Hôpitaux de Paris.
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Chronic Respiratory Failure
- What is being tested?
- Dosage and Cardiac echography
- How many people
- 50 participants
- Where
- No sites listed yet
- Study dates
- Jun 2023to May 2026
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: adult patients with untreated chronic respiratory Ffilure with an indication to oxygen therapy and free from chronic kidney disease.
Who may be able to join
- 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
Who cannot join
- 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 locations and contacts
No sites are listed yet.
About this study
Official title: "Exploration of the Role of Intact Fibroblast Growth Factor 23 and Its C-terminal Fragment in Chronic Respiratory Failure "
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).
Read more
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
- Being tested
- Dosage, Cardiac echography
- Keywords
- fibroblast growth factor 23, erythropoietin, cardiac hypertrophy, pulmonary hypertension, oxygen therapy, chronic respiratory failure
- Medical subject headings
- Cardiomegaly, Hypertension, Pulmonary
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DosageOther
Evaluation of circulating C-terminal FGF23 (FGF23Ct) rate, circulating intact FGF23 (FGF23i) rate and Erythropoietin
Cardiac echographyOther
12 months after patient enrollment
| Study group | Role | What they receive |
|---|---|---|
| incident patients with chronic respiratory failure | adult patients with untreated chronic respiratory failure Receives: Other: Dosage; Other: Cardiac echography |
What is being measured
The primary outcome is the main question the study is designed to answer.
circulating C-terminal FGF23 (FGF23Ct)
ELISA method
Measured: at inclusion (before oxygen therapy)
circulating intact FGF23 (FGF23i)
ELISA method
Measured: at inclusion (before oxygen therapy)
Secondary outcomes (9)
circulating FGF23Ct
ELISA method
Measured: at month 3 and month 12
circulating FGF23i
ELISA method
Measured: at month 3 and month 12
circulating erythropoietin
ELISA method
Measured: at inclusion, month 3 and month 12
arterial O2 saturation
assessed using an arterial sampling
Measured: at inclusion, month 3 (without and with 02 therapy) and month 12 (without and with 02 therapy)
PaO2 (arterial partial oxygen pressure)
assessed using an arterial sampling
Measured: at inclusion, month 3 (without and with 02 therapy) and month 12 (without and with 02 therapy)
Assessment of systolic function
left ventricular ejection fraction assessed using cardiac ultrasound
Measured: at inclusion and month 12
left ventricular mass indexed for body surface area
using cardiac ultrasound
Measured: at inclusion and month 12
Assessment of diastolic function
Recording of mitral filling flow using cardiac ultrasound
Measured: at inclusion and month 12
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
Measured: at inclusion and month 12
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Feb 2022
- Study startJun 2023 (estimated)
- Primary completionMay 2026 (estimated)
- Study completionMay 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Chronic Respiratory FailureStudies of the same condition, open and under way.
- More trials run by Assistance Publique - Hôpitaux de ParisThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Case only
- Time perspective
- Prospective
- Enrolment
- 50 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Assistance Publique - Hôpitaux de Paris
- Sponsor type
- University, hospital or other
- Collaborators
- Fondation Université de Paris
- Responsible party
- Sponsor
- Investigators
- Marie COURBEBAISSE, MD, Study director, Assistance Publique - Hôpitaux de ParisNicolas ROCHE, MD, Principal investigator, Assistance Publique - Hôpitaux de Paris
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05258370
- Sponsor's protocol ID
- APHP201305
- Other IDs
- 2020-A02607-32
- Acronym
- EFIC-RES
- Status last verified
- Apr 2023
- First submitted
- 17 Feb 2022
- Last updated
- 18 Apr 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: Individual participant data (IPD) that underlie results in publication could be shared. IPD detailed in the protocol of a planned metaanalysis could be shared
Publications
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.
PubMed 27789679Clinkenbeard 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.
PubMed 28818868Zhang 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.
PubMed 27468359Faul 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.
PubMed 21985788
Study at a glance
From the registry record, last updated by the sponsor on 18 Apr 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- "Exploration of the Role of Intact Fibroblast Growth Factor 23 and Its C-terminal Fragment in Chronic Respiratory Failure "
- ClinicalTrials.gov ID
- NCT05258370
- Acronym / sponsor ID
- EFIC-RES / APHP201305
- Conditions
- Chronic Respiratory Failure
- Keywords
- fibroblast growth factor 23, erythropoietin, cardiac hypertrophy, pulmonary hypertension, oxygen therapy, chronic respiratory failure
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 50 participants (estimated)
- Lead sponsor
- Assistance Publique - Hôpitaux de ParisUniversity, hospital or other
- Collaborators
- Fondation Université de Paris
- Study start
- Jun 2023 (estimated)
- Primary completion
- May 2026 (estimated)
- Study completion
- May 2026 (estimated)
- First posted
- 28 Feb 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Observational model
- Case only
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| incident patients with chronic respiratory failure | – | Other: Dosage, Other: Cardiac echographyadult patients with untreated chronic respiratory failure |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- adult patients with untreated chronic respiratory Ffilure with an indication to oxygen therapy and free from chronic kidney disease.
Key inclusion criteria (6 listed)
- 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
Key exclusion criteria (8 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| DosageEvaluation of circulating C-terminal FGF23 (FGF23Ct) rate, circulating intact FGF23 (FGF23i) rate and Erythropoietin | Other | incident patients with chronic respiratory failure |
| Cardiac echography12 months after patient enrollment | Other | incident patients with chronic respiratory failure |
Primary outcome
circulating C-terminal FGF23 (FGF23Ct)
Time frame: at inclusion (before oxygen therapy)
ELISA method
circulating intact FGF23 (FGF23i)
Time frame: at inclusion (before oxygen therapy)
ELISA method
9 secondary outcomes
circulating FGF23Ct
Time frame: at month 3 and month 12
circulating FGF23i
Time frame: at month 3 and month 12
circulating erythropoietin
Time frame: at inclusion, month 3 and month 12
arterial O2 saturation
Time frame: at inclusion, month 3 (without and with 02 therapy) and month 12 (without and with 02 therapy)
PaO2 (arterial partial oxygen pressure)
Time frame: at inclusion, month 3 (without and with 02 therapy) and month 12 (without and with 02 therapy)
Assessment of systolic function
Time frame: at inclusion and month 12
left ventricular mass indexed for body surface area
Time frame: at inclusion and month 12
Assessment of diastolic function
Time frame: at inclusion and month 12
Assessment of pulmonary artery pressure
Time frame: at inclusion and month 12
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Apr 2023.
- Background: PubMed 27789679Courbebaisse 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.
- Background: PubMed 28818868Clinkenbeard 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.
- Background: PubMed 27468359Zhang 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.
- Background: PubMed 21985788Faul 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.
- Individual participant dataSharing planned: Yes. Individual participant data (IPD) that underlie results in publication could be shared. IPD detailed in the protocol of a planned metaanalysis could be shared
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Marie COURBEBAISSE, MD study director
Assistance Publique - Hôpitaux de Paris
Nicolas ROCHE, MD principal investigator
Assistance Publique - Hôpitaux de Paris
Questions about this trial
What is this clinical trial studying?
An observational study of Chronic Respiratory Failure, run by Assistance Publique - Hôpitaux de Paris.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 18 Apr 2023. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Natacha Nohilé (331 56 09 59 82, natacha.nohile@aphp.fr), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
circulating C-terminal FGF23 (FGF23Ct) (time frame: at inclusion (before oxygen therapy)). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05258370, which also lists 4 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Apr 2023.