Clinical trial NCT02792413: Study Evaluating Denosumab on Bone and Vascular Metabolism in Osteoporotic Chronic Kidney Disease
Official title: Randomized Controlled Study Evaluating the Effect of a Biotherapy Treatment (Anti-RANKL Ligand Antibody: Denosumab) on Bone and Vascular Metabolism in Osteoporotic Chronic Kidney Disease
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE4
Conditions: Female With Osteoporosis and Chronic Kidney Disease
Keywords: osteoporosis
chronic kidney disease
anti-RANK ligand antibody
bone mineral density
vascular calcifications
Lead sponsor: University Hospital, Montpellier
Sponsor class: OTHER
First posted: 2016-06-07
Enrollment: 4
Sex: FEMALE
Minimum age (years): 65
Maximum age (years): 95
Standard ages: OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Aim of this study is to evaluate in a population of old osteoporotic chronic kidney disease females the effect of denosumab:

* on bone mineral density (femoral T-score) at 24 months
* on bone mineral density evolution (femoral T-score) after 24 months of follow-up
* on bone mineral density evolution (lumbar T-score) after 24 months of follow-up
* on coronary and abdominal aorta calcification scores evolution after 24 months of follow-up
* on parameters of bone remodelling (OPG, RANKL, sclerostin, DKK-1), of mineral and calcium metabolism (FGF23 Ct, Klotho, PTH, 25(OH) vitamin D3, phosphorus, calcium, bone alklaline phosphatase, osteocalcin, CTX), of inflammation (CRP) after 24 months of follow-up
* on cardiovascular morbidity (cardiovascular events) and mortality after 24 months of follow-up
* the tolerance after 24 months of follow-up

Detailed description: Aim of this study is to evaluate in a population of old osteoporotic chronic kidney disease females the effect of denosumab:

* on bone mineral density (femoral T-score) (by bone densitometry) at 24 months
* on bone mineral density evolution (femoral T-score) (by bone densitometry) after 24 months of follow-up
* on bone mineral density evolution (lumbar T-score) (by bone densitometry) after 24 months of follow-up
* on coronary and abdominal aorta calcification scores evolution (by multiple detector computed tomography and plain abdominal X-ray) after 24 months of follow-up
* on parameters of bone remodelling (OPG, RANKL, sclerostin, DKK-1), of mineral and calcium metabolism (FGF23 Ct, Klotho, PTH, 25(OH) vitamin D3, phosphorus, calcium, bone alklaline phosphatase, osteocalcin, CTX), of inflammation (CRP) after 24 months of follow-up
* on cardiovascular morbidity (cardiovascular events) and mortality after 24 months of follow-up
* the tolerance after 24 months of follow-up

Eligibility criteria: Inclusion Criteria:

* Patient of 65 years or older
* Chronic kidney disease stage 5 patient, hemodialyzed with extracorporeal treatment for at least 3 months
* Patient with osteoporosis (history of bone fracture or T-scoring \< -2.5 SD)
* PTH levels in the serum in agreement with the KDIGO guidelines, in the absence of treatment with Cinacalcet.

Exclusion Criteria:

* Cinacalcet treatment
* Calcium parameters (PTH, 25(OH) vitamin D3, Calcium) outside the KDIGO guidelines
* Suspicion of lower bone remodeling
* Hypersensibility to active substance or one of excipients of denosumab
* Patient with a cancer or myeloma
* Patient with severe heaptic cytolysis
* Patients with severe teeth problems
* Patient positive for HIV
* Patient involved in another biomedical research
* Vulnerable patients (protected by the law, under guardianship, deprived of freedom)

Primary outcomes:
measure: Relative variation of femoral bone mineral density after 24 months of follow-up (T-score evaluated by osteodensitometry)
timeFrame: 24 months after inclusion
Secondary outcomes:
measure: Relative variation of lumbar bone mineral density after 24 months of follow-up (T-score evaluated by osteodensitometry)
timeFrame: 24 months after inclusion
measure: Relative variation of coronary calcification scores after 24 months of follow-up
timeFrame: 24 months after inclusion
measure: Relative variation of abdominal aorta calcification scores after 24 months of follow-up
timeFrame: 24 months after inclusion
measure: Variation of calcium at 6, 12, 18 and 24 months of follow-up
timeFrame: 6, 12, 18 and 24 months after inclusion
measure: Variation of phosphorus at 6, 12, 18 et 24 months of follow-up
timeFrame: 6, 12, 18 and 24 months after inclusion
measure: Morbi-mortality at 24 months of follow-up
timeFrame: 24 months after inclusion
measure: Adverse events occuring during the entire study
timeFrame: 24 months after inclusion
Other outcomes:
Locations:
city: Cabestany
country: France
facility: Clinique Médipole Cabestany
city: Castelnau-le-Lez
country: France
facility: CHL Castelnau Le Lez
city: Lyon
country: France
facility: CHU Lyon Sud, Nephrology department
city: Marseille
country: France
facility: AP-HM, Nephrology department
city: Montpellier
country: France
facility: AIDER
city: Montpellier
country: France
facility: CHU Montpellier, Nephrology department
city: Nice
country: France
facility: CHU Nice, Nephrology department
city: Nimes
country: France
facility: CHU Nimes, Nephrology department
city: Perpignan
country: France
facility: CH Perpignan, Nephrology department
Study officials:
affiliation: CHU Lapeyronie, Department of Biochemistry and Hormonology, Montpellier, FRANCE
name: Jean-Paul CRISTOL, Prof
role: PRINCIPAL_INVESTIGATOR
References:
citation: Hara T, Hijikata Y, Matsubara Y, Watanabe N. Pharmacological interventions versus placebo, no treatment or usual care for osteoporosis in people with chronic kidney disease stages 3-5D. Cochrane Database Syst Rev. 2021 Jul 7;7(7):CD013424. doi: 10.1002/14651858.CD013424.pub2.