Effect of Active Vitamin D and Etelcalcetide on Human Osteoclasts in Patients With Chronic Kidney Disease (RENOCLASTE)
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT03527511|
Recruitment Status : Recruiting
First Posted : May 17, 2018
Last Update Posted : June 7, 2018
The optimal management of mineral and bone disorders associated to chronic kidney disease (CKD-MBD) is a daily challenge for nephrologists. Its consequences may be immediate (biological abnormalities such as hypocalcemia, hyperphosphatemia, hyperparathyroidism, etc.) or delayed (fractures, renal osteodystrophy, vascular calcifications, increased morbi-mortality and growth retardation in the youngest patients). CKD-MBD is defined by the association of one or more of the following abnormalities: 1/ disturbances in calcium, phosphate, PTH or vitamin D metabolism, 2/ bone and growth abnormalities, and 3/ calcifications of vessels or soft tissues .
Three main bone characteristics can be modified by CKD, namely turnover, mineralization and volume. They should therefore be carefully assessed to distinguish between the different sub-types of renal osteodystrophy, as defined in the 2006 K-DIGO guidelines on the TMV classification . The primary bone lesion in pediatric CKD, at least in pediatric patients reaching end-stage renal disease without any previous management, is the high-turnover/hyperparathyroidism, because of high circulating PTH levels with low 1-25 vitamin D levels. Conversely, low turnover (or adynamic bone) may be observed in dialysis children receiving too much calcium and/or vitamin D analogs. All these lesions are deleterious on the long-term, increasing both the risk of growth retardation, fractures and vascular calcifications .
In order to better understand the complex pathophysiology of renal osteodystrophy, biomarkers of bone and phosphate/calcium metabolism may be used, but their interpretation may be challenging in the context of CKD. The gold standard remains bone biopsy at the iliac crest with histomorphometry, but it is rarely performed in Europe .
The research team of this study has developed and validated a unique non-invasive technique to differentiate circulating human monocytes into mature and functional osteoclasts, using only 15 mL of total blood (instead of conventional techniques they used to use, with 200 to 250 mL of total blood). They propose to use this innovative tool in the specific setting of CKD.
The current management of CKD-MBD consists mainly of correcting native vitamin D deficiency, decreasing phosphate levels (using nutritional management and phosphate-binders), and decreasing PTH levels (using active vitamin D, calcimimetics such as cinacalcet and etelcalcetide, and/or surgical parathyroidectomy) . Active vitamin D analogs and calcimimetics are cornerstone of this management.
The first working hypothesis is the following: when CKD progresses and glomerular filtration rate (GFR) decreases, 1-25-D is able to inhibit osteoclastic differentiation, however to a lesser extent to what is observed in healthy controls with normal renal function.
The second working hypothesis is therefore the following: etecalcetide could be an inhibitor of osteoclastic resorption and a stimulator of osteoblastogenesis. When CKD worsens and GFR decreases, etelcalcetide inhibits osteoclastic differentiation, however to a lesser extent to what is observed in subjects with normal renal function.
Aims In Vitro
- Effects of 1-25-D and etecalcetide on human osteoclastogenesis and osteoclastic resorption (in cells obtained from CKD patients at different stages of CKD)
- Effects of 1-25-D and etecalcetide on murine osteoblastogenesis and mineralization
|Condition or disease||Intervention/treatment|
|Bone Disorder Chronic Kidney Diseases||Other: Measure of etecalcetide on osteoclastic biology|
|Study Type :||Observational|
|Estimated Enrollment :||35 participants|
|Official Title:||Effect of Active Vitamin D and Etelcalcetide on Human Osteoclasts in Patients With Chronic Kidney Disease|
|Actual Study Start Date :||May 14, 2018|
|Estimated Primary Completion Date :||May 14, 2020|
|Estimated Study Completion Date :||May 14, 2020|
- Other: Measure of etecalcetide on osteoclastic biology
In vitro evaluation of osteoclastic biology after blood sampling of patients.
- Active vitamin D action on osteoclasts [ Time Frame: 1 day ]Patients' cells will be used to ex vivo. Osteoclastic biology will be analyzed according to two components: differentiation and resorption activity.
- Etecalcetide action on osteoclasts [ Time Frame: 1 day ]Patients' cells will be used to ex vivo. Osteoclastic biology will be analyzed according to two components: differentiation and resorption activity.
Biospecimen Retention: Samples Without DNA
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03527511
|Contact: Justine BACCHETTA, Pr||04 27 85 61 30 ext +firstname.lastname@example.org|
|Service de Néphrologie, Rhumatologie et Dermatologie Pédiatriques - Hôpital Femme Mère Enfant - Bron.||Recruiting|
|Bron, France, 69677|
|Contact: Justine BACCHETTA, Pr 04 27 85 61 30 ext +33 email@example.com|
|Principal Investigator: Justine BACCHETTA, Pr|
|Sub-Investigator: Bruno RANCHIN, Dr|
|Sub-Investigator: Anne-Laure SELIER-LECLERC, Dr|
|Sub-Investigator: Aurélia BERTHOLET-THOMAS, Dr|
|Sub-Investigator: Elodie CHEYSSAC, Dr|
|Sub-Investigator: Corentin TANNE, Dr|