Clinical trial NCT02299817: Denosumab for Treating Periprosthetic Osteolysis.
Official title: Denosumab for Treating Periprosthetic Osteolysis After Uncemented Total Hip Arthroplasty A Randomized, Double-blind, Placebo-controlled Trial Using Volumetric Computed Tomography
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Osteolysis
Lead sponsor: Danderyd Hospital
Sponsor class: OTHER
Collaborators: name: Danderyd Hospital
First posted: 2014-11-24
Enrollment: 20
Sex: ALL
Minimum age (years): 40
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: 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).


Eligibility 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.

Primary outcomes:
measure: Volume of the osteolytic lesion
timeFrame: 3 years
Secondary outcomes:
measure: Volume of the osteolytic lesion
timeFrame: 2 years
measure: Percentage change of the lesion over the study period
timeFrame: 3 years
measure: Adverse events
timeFrame: 3 years
Other outcomes:
Locations:
city: Stockholm
country: Sweden
facility: Danderyd Hospital
Study officials:
affiliation: Danderyds Hospital
name: Olof Sköldenberg, MD, Ph.D
role: STUDY_DIRECTOR
References:
citation: Skoldenberg O, Rysinska A, Eisler T, Salemyr M, Boden H, Muren O. Denosumab for treating periprosthetic osteolysis; study protocol for a randomized, double-blind, placebo-controlled trial. BMC Musculoskelet Disord. 2016 Apr 23;17:174. doi: 10.1186/s12891-016-1036-5.