"Exploration of the Role of Intact Fibroblast Growth Factor 23 and Its C-terminal Fragment in Chronic Respiratory Failure "
试验速览
- 阶段
- 不适用
- 状态
- 尚未招募
- 入组人数
- 50
- 主要终点
- circulating C-terminal FGF23 (FGF23Ct)
研究概览
简要总结
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.
研究设计
- 研究类型
- Observational
- 观察模型
- Case Only
- 时间视角
- Prospective
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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
结局指标
主要结局
circulating C-terminal FGF23 (FGF23Ct)
时间窗: at inclusion (before oxygen therapy)
ELISA method
circulating intact FGF23 (FGF23i)
时间窗: at inclusion (before oxygen therapy)
ELISA method
次要结局
- circulating erythropoietin(at inclusion, month 3 and month 12)
- left ventricular mass indexed for body surface area(at inclusion and month 12)
- PaO2 (arterial partial oxygen pressure)(at inclusion, month 3 (without and with 02 therapy) and month 12 (without and with 02 therapy))
- Assessment of systolic function(at inclusion and month 12)
- Assessment of diastolic function(at inclusion and month 12)
- arterial O2 saturation(at inclusion, month 3 (without and with 02 therapy) and month 12 (without and with 02 therapy))
- Assessment of pulmonary artery pressure(at inclusion and month 12)
- circulating FGF23Ct(at month 3 and month 12)
- circulating FGF23i(at month 3 and month 12)