Effect of Denosumab on Inflammatory Osteolytic Lesion Activity in Total Hip Arthroplasty

NCT01358669 | Completed Phase 2

• 1 other identifier: STH15714
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief Summary

Although hip replacement surgery is a successful way of dealing with the pain and immobility caused by hip arthritis, 10% of the hip replacements carried out in the UK fail within 10 years. The main reason for this is the development periprosthetic osteolysis, that is, loss of bone around the site of the hip replacement. The osteolysis is thought to be due to the small particles of debris worn from the surfaces of the hip implant. These particles cause a reaction in the blood cells around the joint which in turn affects bone cells and leads to a loss of bone around the implant. The joint implant will then eventually become loose and unstable, a condition known as aseptic loosening. At present the only way to treat aseptic loosening is to have another operation to secure the hip joint, known as revision surgery. Revision surgery is not always successful and exposes the patient to the risk of major surgery. In this study we explore the potential for giving a medication (denosumab) that may prevent the loss of bone around the hip replacement implant. We will recruit patients who have been listed for revision surgery. One group of patients will be given a single dose of denosumab; another group will be given a placebo (dummy drug). At the time of the revision surgery a small sample of the bone from around the hip replacement will be taken and examined under the microscope. Comparisons will be made between the patients having the denosumab and those having placebo to find out whether the denosumab is having a beneficial effect on the bone surfaces. If successful, this study will lead to further studies to develop the use of denosumab to prevent aseptic loosening.

Conditions

Revision Surgery of Total Hip Arthroplasty

Keywords

Denosumab; Total Hip Arthroplasty

Outcome Measures

Primary Outcomes (1)

• Osteoclast number

  Absolute difference between study groups in osteoclast number per millimetre at the osteolysis membranebone interface, measured by cell counting in histological sections between the denosumab and placebo groups, 8 weeks after administration of the IMP

  8 weeks after administration

Secondary Outcomes (3)

• Change in serum or urine levels of βCTXI, NTXI/Cr, TRAcP5b, CTXMMP, PINP, OPG, RANKL

  8 weeks after administration of the IMP

• Difference between the denosumab and placebo groups in mean eroded, quiescent, and osteoblast surfaces at the membrane bone interface

  8 weeks after administration of the IMP

• Difference between the denosumab and placebo groups in ratio of viable to apoptotic osteoclast, macrophage fibroblast, and osteoblasts by TUNEL staining and relative number of cells staining positive for apoptosis markers

  8 weeks after administration of the IMP

Study Arms (2)

Denosumab

ACTIVE COMPARATOR

In this study we explore the potential for giving a medication (denosumab) that may prevent the loss of bone around the hip replacement implant

Drug: Denosumab

Placebo

PLACEBO COMPARATOR

Placebo

Other: Placebo

Interventions

Denosumab DRUG

60mg denosumab by injection as a single dose

Also known as: Prolia

Denosumab

Placebo OTHER

Placebo by injection as a single dose

Placebo

Eligibility Criteria

• Age: 30 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participants must be men or women over 30 years of age undergoing revision THA surgery for periprosthetic osteolysis / aseptic loosening affecting the pelvis and / or femur.
• Participants must also be willing and able to give fully informed consent.
• Participants must have osteolysis / aseptic loosening affecting fully cementless, hybrid, or fully cemented THA prosthesis

You may not qualify if:

• Known prosthesis infection
• Pregnancy / Breast feeding
• Oral bisphosphonate therapy (current use, previous use within the last 12 months, previous 3 or more years cumulative use)
• Administration of intravenous bisphosphonate, fluoride or strontium within the last 5 years
• Participation in ongoing or previous denosumab clinical trials
• Administration of any of the following treatments within the last 12 months
• TH or PTH derivatives, eg, teriparatide
• anabolic steroids or testosterone
• glucocorticosteroids (\> 5 mg prednisone equivalent per day for more than 10 days)
• systemic hormone replacement therapy
• selective estrogen receptor modulators (SERMs), eg, raloxifene tibolone, calcitonin or calcitriol
• Any subject in whom denosumab is contraindicated according to the local SmPC of denosumab (SC 60 mg every 6 months in UK)
• Current hypocalcemia (albumin adjusted serum calcium below 2.13 mmol/L)
• History of rheumatoid arthritis
• History of Paget's disease

Sponsors & Collaborators

• Sheffield Teaching Hospitals NHS Foundation Trust: lead
• Amgen: collaborator
• University of Sheffield: collaborator

Study Sites (1)

Academic Unit of Bone Metabolism

Sheffield, South Yorkshire, S5 7AU, United Kingdom

Location

MeSH Terms

Interventions

Denosumab

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• J M Wilkinson, PhD, FRCS (Tr&Orth)

  Sheffield Teaching Hospitals NHS Foundation Trust/University of Sheffield

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 11, 2011
• First Posted: May 24, 2011
• Study Start: December 14, 2011
• Primary Completion: January 2, 2019
• Study Completion: December 31, 2021
• Last Updated: August 29, 2022

Record last verified: 2019-11

Locations

GB (1)