We are updating the design of this site. Learn more.
Show more
ClinicalTrials.gov
ClinicalTrials.gov Menu

Denosumab for Treating Periprosthetic Osteolysis.

This study is currently recruiting participants.
Verified August 2016 by Olof Skoldenberg, Danderyd Hospital
Sponsor:
ClinicalTrials.gov Identifier:
NCT02299817
First Posted: November 24, 2014
Last Update Posted: August 30, 2016
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.
Collaborator:
Danderyd Hospital
Information provided by (Responsible Party):
Olof Skoldenberg, Danderyd Hospital
  Purpose
The main objective is to study the efficacy of denosumab in reducing wear-induced osteolysis around uncemented acetabular implants used in total hip arthroplasty. Patients included in the study will receive the same dose of 60 mg denosumab or placebo (1 ml solution) for a total of 6 doses with start on day one and every 6 months with last treatment at 30 months. The primary endpoint will be the change in volume of the osteolytic lesion over 3 years measured (measured with 3D-CT in cm³).

Condition Intervention Phase
Osteolysis Drug: Denosumab Drug: Placebo Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Prevention
Official Title: Denosumab for Treating Periprosthetic Osteolysis After Uncemented Total Hip Arthroplasty A Randomized, Double-blind, Placebo-controlled Trial Using Volumetric Computed Tomography

Resource links provided by NLM:


Further study details as provided by Olof Skoldenberg, Danderyd Hospital:

Primary Outcome Measures:
  • Volume of the osteolytic lesion [ Time Frame: 3 years ]
    The change in volume of the osteolytic lesion over 3 years (measured with 3D-CT in cm³) is the primary endpoint variable: E〖fficacy〗_(3 years)=〖Volume〗_(3 years)-〖Volume〗_baseline.


Secondary Outcome Measures:
  • Volume of the osteolytic lesion [ Time Frame: 2 years ]
    The change in volume of the osteolytic lesion over 2 years (measured with 3D-CT in cm³) 〖Efficacy〗_(2 years)=〖Volume〗_(2 years)-〖Volume〗_baseline.

  • Percentage change of the lesion over the study period [ Time Frame: 3 years ]
    Percentage change of the lesion over the study period

  • Adverse events [ Time Frame: 3 years ]
    Occurrence of AE´s


Estimated Enrollment: 110
Study Start Date: August 2015
Estimated Study Completion Date: February 2021
Estimated Primary Completion Date: January 2021 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Denosumab
Patients will receive a dose of 60 mg denosumab (1 ml solution) for a total of 6 doses with start on day one and every 6 months with last treatment at 30 months.
Drug: Denosumab

Prolia is used to treat osteoporosis (a disease that makes bones fragile) in women who have been through the menopause and in men who have an increased risk of fracture (broken bones). In women who have been through the menopause Prolia reduces the risk of fractures in the spine and elsewhere in the body, including in the hip.

Prolia is also used to treat bone loss in men receiving treatment for prostate cancer that increases their risk of fracture. Prolia reduces the risk of fractures in the spine.

Recently denosumab was found to be effective in preventing osteoporosis related fractures in post-menopausal women by blocking RANKL and thereby inhibiting the development and activity of osteoclast.

Other Name: Prolia
Placebo Comparator: Placebo
Patients will receive a dose of placebo (1 ml solution) for a total of 6 doses with start on day one and every 6 months with last treatment at 30 months.
Drug: Placebo
Placebo

  Eligibility

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   40 Years to 85 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Age 40-85 years
  • Short Portable Mental Status Questionnaire (SPMSQ) also named pfeiffers test ≥7
  • Male and females
  • The primary total hip arthroplasty performed between 7 to 20 years before inclusion.
  • The primary total hip arthroplasty performed due to osteoarthritis or congenital dysplasia of the hip.
  • Uncemented cup fixation
  • Baseline osteolytic lesion of at least 4 cm³ and at most 40 cm³ around an uncemented acetabular component with a polyethylene liner.
  • Participant is willing and able to follow study protocol and has provided informed consent prior to any study specific procedures.

Exclusion Criteria:

  • For women of childbearing potential: Subject refuses to use 1 highly effective method of contraception (contraceptive pill, intra uterine contraceptive device) for the duration of the study and for 10 months after the last dose of study medication.
  • For males with a partner of childbearing potential: Subject refuses to use a condom for the duration of the study and for 10 months after the last dose of study medication.
  • For males with a partner who is pregnant: Subject refuses to use a condom for the duration of the study and for 10 months after the last dose of study medication.
  • Pain in the operated hip (because the presence of hip pain in combination with an osteolytic lesion is an indication for revision surgery). VAS >3
  • Previous revision surgery of the hip i.e. exchange of any inplant after the primary surgery
  • Inflammatory arthritis
  • Previous participation in clinical trials with denosumab or administration of commercial denosumab (Prolia™ or Xgeva™)
  • Currently enrolled in or has not yet completed at least 1 month since ending other investigational device or drug trial(s), or subject is receiving other investigational agent(s).
  • Treatment with any intravenous bisphosphonate, fluoride (except for dental treatment) or strontium ranelate within 5 years prior to inclusion.
  • Treatment with any oral bisphosphonate within 1 year prior to inclusion.
  • Treatment with cortisol or cytostatic drugs within 6 months prior to inclusion.
  • Administration of any of the following treatments 3 months prior to screening:

    • Anabolic steroids or testosterone
    • Glucocorticosteroids (≥ 5 mg prednisone equivalent per day for more than 10 days or a total cumulative dose of ≥ 50 mg)
    • Calcitonin
    • Calcitriol or vitamin D derivatives [vitamin D contained in supplements or multivitamins is allowed]
    • Other bone active drugs including anti convulsive (except benzodiazepines) and heparin
    • Chronic systemic ketoconazole, adrenocorticotrophic hormone, cinacalcet, aluminum, lithium, protease inhibitors, methotrexate, gonadotropin-releasing hormone agonists.
    • Androgen deprivation therapy
  • Hypocalcaemia.
  • Bone metabolic disorders (such as OI, PHPT, Paget)
  • History of osteonecrosis of the jaw and/or recent tooth extraction or dental surgery; or planned invasive dental procedures during the study
  • Serum 25-OH D <20 ng/ml
  • Significant malabsorption including Celiac Disease, Short Bowel Syndrome, Crohn's Disease, Previous Gastric Bypass.
  • Active cancer and/or malignancy in last 5 years (except cervical carcinoma in situ or basal cell carcinoma)
  • History of solid organ or bone marrow transplant.
  • Hypersensitivity to any components of study drug.
  • Intolerance to calcium supplements.
  • Pregnancy and/or currently lactating.
  • Significantly impaired renal function as determined by a derived glomerular filtration rate (GFR) using Cockcroft Gault formula of 30 mL/min/1.73 m2
  • Elevated transaminases ≥ 2.0 x upper limit of normal (ULN); Elevated total bilirubin (TBL) > 1.5 x ULN.
  • Any condition or illness (acute, chronic, or history), which in the opinion of the Investigator might interfere with the evaluation of efficacy and safety during the study or may otherwise compromise the safety of the subject.
  Contacts and Locations
Information from the National Library of Medicine

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): NCT02299817


Contacts
Contact: Olof Sköldenberg, MD, Ph.D +46 70 089 12 53 olof.skoldenberg@ki.se

Locations
Sweden
Danderyd Hospital Recruiting
Stockholm, Sweden, 182 88
Contact: Olof Skoldenberg, MD, PhD    +46 8 123 5 7245    olof.skoldenberg@gmail.com   
Contact: Paula Kelly-Pettersson, RN, BSN    +46 8 12356104    paula-therese.kelly-pettersson@ds.se   
Principal Investigator: Olof Sköldenberg, MD, PhD         
Sponsors and Collaborators
Olof Skoldenberg
Danderyd Hospital
Investigators
Study Director: Olof Sköldenberg, MD, Ph.D Danderyds Hospital
  More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Olof Skoldenberg, MD PhD, Danderyd Hospital
ClinicalTrials.gov Identifier: NCT02299817     History of Changes
Other Study ID Numbers: EudraCT No: 2013-004940-48
First Submitted: November 20, 2014
First Posted: November 24, 2014
Last Update Posted: August 30, 2016
Last Verified: August 2016

Additional relevant MeSH terms:
Osteolysis
Bone Resorption
Bone Diseases
Musculoskeletal Diseases
Denosumab
Bone Density Conservation Agents
Physiological Effects of Drugs