Study Evaluating Denosumab on Bone and Vascular Metabolism in Osteoporotic Chronic Kidney Disease (HDENO)

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

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

Study Overview

• Status: Terminated
• Conditions: Female With Osteoporosis and Chronic Kidney Disease
• Intervention / Treatment: Drug: Denosumab; Drug: NaCl (placebo)

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

• Study Type: Interventional
• Enrollment (Actual): 4
• Phase: Phase 4

Contacts and Locations

Study Locations

• France
  • Cabestany, France
    • Clinique Médipole Cabestany
  • Castelnau-le-Lez, France
    • CHL Castelnau Le Lez
  • Lyon, France
    • CHU Lyon Sud, Nephrology department
  • Marseille, France
    • AP-HM, Nephrology department
  • Montpellier, France
    • AIDER
  • Montpellier, France
    • CHU Montpellier, Nephrology department
  • Nice, France
    • CHU Nice, Nephrology department
  • Nimes, France
    • CHU Nimes, Nephrology department
  • Perpignan, France
    • CH Perpignan, Nephrology department

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 61 years to 91 years (Older Adult)
• Accepts Healthy Volunteers: No

Description

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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Denosumab; Denosumab 60 mg, subcutaneous injection every 6 months for 24 months	Drug: Denosumab; Patients will receive a subcutaneous injection of Denosumab every 6 months for the duration of the study. In addition, they will receive vitamin D and calcium (which is the normal treatment) for the duration of the study.
Placebo Comparator: Placebo; NaCl 0.9% (1 mL), subcutaneous injection every 6 months for 24 months	Drug: NaCl (placebo); Patients will receive a subcutaneous injection of NaCl every 6 months for the duration of the study. In addition, they will receive vitamin D and calcium (which is the normal treatment) for the duration of the study.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Relative variation of femoral bone mineral density after 24 months of follow-up (T-score evaluated by osteodensitometry)	24 months after inclusion

Secondary Outcome Measures

Outcome Measure	Time Frame
Relative variation of lumbar bone mineral density after 24 months of follow-up (T-score evaluated by osteodensitometry)	24 months after inclusion
Relative variation of coronary calcification scores after 24 months of follow-up	24 months after inclusion
Relative variation of abdominal aorta calcification scores after 24 months of follow-up	24 months after inclusion
Variation of calcium at 6, 12, 18 and 24 months of follow-up	6, 12, 18 and 24 months after inclusion
Variation of phosphorus at 6, 12, 18 et 24 months of follow-up	6, 12, 18 and 24 months after inclusion
Morbi-mortality at 24 months of follow-up	24 months after inclusion
Adverse events occuring during the entire study	24 months after inclusion

Collaborators and Investigators

• Sponsor: University Hospital, Montpellier
• Investigators: Principal Investigator: Jean-Paul CRISTOL, Prof, CHU Lapeyronie, Department of Biochemistry and Hormonology, Montpellier, FRANCE

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): November 19, 2018
• Primary Completion (Actual): December 10, 2020
• Study Completion (Actual): December 10, 2020

Study Registration Dates

• First Submitted: June 2, 2016
• First Submitted That Met QC Criteria: June 6, 2016
• First Posted (Estimated): June 7, 2016

Study Record Updates

• Last Update Posted (Actual): August 9, 2023
• Last Update Submitted That Met QC Criteria: August 8, 2023
• Last Verified: April 1, 2022

More Information

Terms related to this study

• Keywords: chronic kidney disease; osteoporosis; vascular calcifications; bone mineral density; anti-RANK ligand antibody
• Additional Relevant MeSH Terms: Pathologic Processes; Metabolic Diseases; Urologic Diseases; Disease Attributes; Renal Insufficiency; Musculoskeletal Diseases; Bone Diseases; Bone Diseases, Metabolic; Chronic Disease; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Kidney Diseases; Renal Insufficiency, Chronic; Osteoporosis; Physiological Effects of Drugs; Bone Density Conservation Agents; Denosumab
• Other Study ID Numbers: RECHMPL15_0496; UF 9676 (Other Identifier: Montpellier University Hospital)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No