Clinical trial NCT01220843: FGF23 Reduction : Efficacy of a New Phosphate Binder in CHronic Kidney Disease
Official title: Randomized Placebo Controlled Double-blind Trial in CKD Patients Not on Dialysis to Evaluate the Effect of Sevelamer Carbonate in the Control of FGF-23 Serum Levels and Its Consequences in the Evolution of PTH, Calcitriol and Mineral Metabolism Parameters Levels
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Chronic Renal Failure
Keywords: chronic renal failure
FGF23
Sevelamer carbonate
Lead sponsor: Centre Hospitalier Universitaire, Amiens
Sponsor class: OTHER
Collaborators: name: Genzyme, a Sanofi Company
First posted: 2010-10-14
Enrollment: 98
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to evaluate in Chronic Kidney Disease (CKD) patients not on dialysis and who have an Fibroblast growth factor 23 (FGF23) serum levels elevated, the effect of non calcic phosphate binder: sevelamer carbonate. This treatment could lead to a diminution of FGF23 serum levels due to the diminution of intestinal absorption of dietary phosphate. In addition, the investigators will describe the impact of the FGF23 level monitoring on the main phosphocalcium metabolism markers as phosphatemia, intact parathyroid hormone (iPTH), serum calcitriol and phosphaturia.

Detailed description: The total length of the study is 14 weeks divided in 2 parts the first part is the screening period she will stay 1 to 2 weeks and the second period with the treatment with permanent dosage during 12 weeks.

During the screening visit (Vo) inclusion and non inclusion criteria will be checked and the patient consent will be collected. Biological analysis will be performed.

If the patient still eligible after the reception of biological results, he will be randomized and will received, either sevelamer carbonate, either placebo. The study treatment will be begun at the randomisation visit (V1) the dosage will be 2 tablets 3 times per day (corresponding to 4.8g/d sevelamer carbonate for patient taken active medication).

Patient will be seen every 2 weeks after the first visit (+/-5days) during 6 weeks (visit2/day15, visit3/day30, visit4/day45) and 12 weeks after the randomisation visit (visit5/day90). This visits will include biological analysis, compliance evaluation, adverse events report, concomitant treatments reports.

After the consent signature, all the adverse events will be collected until the end of the study for the patient (Visit5 or end of the study visit). Serious adverse events will be collected until 30 days after the date of the end of the study.

The same dosage of the study treatment will be followed during all the study period except if the phosphatemia (evaluated during one analysis) is found above the normal range planned by the protocol. In this case, the dosage adaptations will be :

* If during a visit the phosphatemia is above or equal to 0.8 mmol/l and superior to 0.5 mmol/l, the study treatment dosage need to be reduce to 2 tablets 3 times per day to 1 tablet 3 times per day.
* If during the next blood punction, the phosphatemia still or equal to 0.8 mmol/l and superior to 0.5 mmol/l, the study treatment will be stopped and a "end of study" visit will be performed.
* If during one study visit, the phosphatemia is above or equal to 0.5 mmol/l,the study treatment will be stopped immediately and a end of study visit will be performed.

Eligibility criteria: Inclusion Criteria:

* Patients who gave their written consent
* Women or men over 18 years
* No concomitant treatment with phosphate binders
* CKD patients not on dialysis stage 3b or 4, as a GFR (glomerular filtration rate) between 15 and 45 ml/min/1.73m2, using simplified MDRD formula
* At the inclusion visit,patients with blood results as levels of C-terminal FGF-23 \> 120 rU/ml and fasting phosphatemia \> 1.0 mmol/l
* Able to comply with the study procedures during all the study period
* Willing to abstain from taking any following medication during all the study period :antiacid and phosphate binders with aluminium, magnesium, calcium or lanthanum;Treatment for hyperparathyroid : active vitamin D and calcimimetic ; native vitamin D
* Female subjects who are of childbearing potential must have a reliable contraceptive methods during all the study period (hormonal, barrier methods or intrauterine device)
* No Participation in any clinical trial using an investigational product or device during the 30 days preceding the first protocol visit
* Informed patient who agreed with the utilisation of his data for the study
* Able to read and understand french and study objectives
* Inscription to medical assurance

Exclusion Criteria:

* predisposition with or presence of intestinal or ileus obstruction or severe gastrointestinal motility disorder(like severe constipation)
* Antecedent of major gastrointestinal surgery
* Abusive consumption of alcohol and drug (exclude tabacco) according the investigator
* Arrythmia treated by antiarrythmic agent or epilepsia treated by anticonvulsant
* Antecedent of kidney transplantation
* Antecedent of parathyroidectomy
* At the inclusion visit,patients with blood results as fasting phosphatemia \> 1.78 mmol/l or serum 25(OH)D3\< 20 ng/ml (\<50 nmol/)
* Pregnancy or breastfeeding

Primary outcomes:
measure: Measurement of the serum levels of C terminal segment of fibroblast growth factor 23 (FGF23) and evaluation of sevelamer carbonate effect on this levels in comparison with placebo
timeFrame: 12 weeks after the beginning of treatment
Secondary outcomes:
measure: Evaluation of sevelamer carbonate effect on the serum levels of iPTH
timeFrame: 12 weeks after the beginning of treatment
measure: Evaluation of sevelamer carbonate effect on the serum levels of calcitriol (1 25(OH)2D3)
timeFrame: 12 weeks after the beginning of treatment
measure: Evaluation of sevelamer carbonate effect on the serum levels of others mineral metabolism parameters (phosphore, calcium, intact FGF-23 , 25(OH)D3, bone specific alkaline phosphatases, osteocalcin, collagen crosslink, C reactive protein)
timeFrame: 12 weeks after the beginning of treatment
measure: Evaluation of sevelamer carbonate effect on the urinary levels of phosphate
timeFrame: 12 weeks after the beginning of treatment
measure: Evaluation of sevelamer carbonate effect on the urinary levels of calcium
timeFrame: 12 weeks after the beginning of treatment
measure: Evaluation of sevelamer carbonate effect on the urinary levels of creatinine
timeFrame: 12 weeks after the beginning of treatment
measure: Evaluation of sevelamer carbonate effect on the urinary levels of urea
timeFrame: 12 weeks after the beginning of treatment
measure: Evaluation of sevelamer carbonate effect on the serum and urinary levels of specific biomarkers (serum : fetuin A, para-cresyl sulfate, osteopontin)
timeFrame: 12 weeks after the beginning of treatment
Other outcomes:
Locations:
city: Amiens
country: France
facility: CHU Amiens service de nephrologie
city: Bordeaux
country: France
facility: CHU de Bordeaux Service de néphrologie
city: Caen
country: France
facility: CHU Caen service de néphrologie
city: Lyon
country: France
facility: CHU Lyon service de néphrologie
city: Marseille
country: France
facility: CHU Marseille Service de néphrologie
city: Montpellier
country: France
facility: CHU de Montpellier Hôpital Lapeyronie Service de Néphrologie
city: Nice
country: France
facility: CHU de Nice Service de néphrologie
city: Paris
country: France
facility: Hôpital Tenon Service de Nephrologie
city: Paris
country: France
facility: Hôpital Européen Georges Pompidou Service de Nephrologie
city: Reims
country: France
facility: CHU Reims service de néphrologie
city: Saint Ouen
country: France
facility: Clinique du Landy Centre de dialyse
city: St Etienne
country: France
facility: CHU St Etienne Hopital Nord Service de néphrologie
city: TASSIN la Demi Lune
country: France
facility: Néphrologie - Dialyse Centre de Rein Artificiel
city: Valenciennes
country: France
facility: CH Valenciennes hémodialyse
city: Vandeuvre les Nancy
country: France
facility: CHU de Nancy service de néphrologie
Study officials:
affiliation: Centre Hospitalier Universitaire, Amiens
name: Gabriel Choukroun, Ph D, M D
role: PRINCIPAL_INVESTIGATOR
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