Effects of Denosumab on Periprosthetic Bone After Total Hip Arthroplasty

Osteoarthritis, Hip Clinical Trial

Official title:

Uncemented Total Hip Implant and Subcutaneous Injections of Denosumab for Patients With Osteoarthritis of the Hip. A Randomized Double Blind Placebo Controlled Study on the Effects on Bone Evaluated With DXA, PET/CT and Biochemical Markers

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01630941
• Other study ID #: 2011-001481-18
• Status: Completed
• Phase: Phase 2
• First received: June 26, 2012
• Last updated: April 4, 2017
• Start date: August 7, 2012
• Est. completion date: March 30, 2017

Study information

• Verified date: April 2017
• Source: Uppsala University Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The primary objective is to study the effect of Denosumab on Bone Mineral Density, Standardised Uptake Value and bone metabolism in patients with total hip arthroplasty. The primary hypothesis is to demonstrate that Denosumab is superior to placebo.

Description:

A clinical study with 64 patients, age 35-65 years, with unilateral osteoarthritis of the hip, randomised to two groups of patients, either receiving Denosumab or placebo

The patients will operated with an uncemented total hip arthroplasty with a Continuum acetabular cup with trabecular surface (Tantalum) and longevity Highly Cross-linked Polyethylene liner, Zimmer, Warsaw, IN, USA, and a CFP femoral stem with Titanium surface and a chrome cobalt 28 mm head, Waldemar Link, Hamburg, Germany.

Clinical outcome evaluated by Harris Hip Score and EQ-5D, Bone Mineral Density by DXA, Standardised Uptake Value of Fluoride tracer, by PET/CT and biochemical markers for bone formation and bone resorption will be analyzed together with conventional radiology for implant position and fixation.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 64
• Est. completion date: March 30, 2017
• Est. primary completion date: January 16, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 35 Years to 65 Years

Eligibility

Inclusion Criteria:

1. male or female patient 35-65 years of age with an unilateral OAH requiring a THA and a healthy contralateral hip

2. body weight =110 kg or body mass index (BMI) =35 kg/m2

3. living in the Uppsala County

4. the eligible patients should have been given oral information, a written Patient Information and signed an Informed Consent

Exclusion Criteria:

1. on or previously have had bone-specific treatment, e.g. bisphosphonates, raloxifene, parathyroid hormone, strontium ranelate, during the last five years

2. patients on systemical corticosteroid for more than 3 months should not be considered

3. patients with diagnosed malignant disease during the last five years or known to have metastasis from malignant disease should be excluded

4. patients with compromised general conditions and an American Society of Anesthesiologists, ASA-score >31 should not be regarded eligible

5. patients with known drug or alcohol abuse or regarded as socially dysfunctional, as judged by the investigator, should not be considered for the study

6. pregnant women or women planning for pregnancy or fertile women (premenopausal) without contraceptives should not be accepted for the study

7. patients that have been exposed frequently and/or have had large irradiation doses, as judged by the investigator, must not be included in the study.

8. enrolled in either another investigational drug study, in another investigational device study, or in another investigational study of an approved drug within 30 days prior to Visit 1 of the current study

9. any condition or laboratory findings which in the opinion of the Investigator makes the patient unsuitable for inclusion (for example claustrophobia)

Related Conditions & MeSH terms

• Ambulation Difficulty
• Mobility Limitation
• Osteoarthritis
• Osteoarthritis, Hip

Intervention

Drug:
• denosumab
Two doses of 60 mg in a solution of 1 ml, given as an subcutaneous injection with a 6 month interval

Locations

Country	Name	City	State
Sweden	Department of Orthopedics	Uppsala

Sponsors (1)

Lead Sponsor	Collaborator
Hans Mallmin

Country where clinical trial is conducted

Sweden, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Bone Mineral Density	Bone mineral density by DXA in Gruen Zone 7 and a sum of Gruen zone 1-7	12 months
Secondary	Bone mineral Density	BMD, g/cm2, adjacent to the femur implant for Gruen Zone 1-7, 3, 6, and 24 months after surgery	24 months
Secondary	Standardised Uptake value	fluoride isotope uptake, measured as (SUV), adjacent to the femoral stem, 3 and 6 months after surgery.	6 months
Secondary	Standardised Uptake value	fluoride isotope uptake, measured as SUV adjacent to the acetabular cup 3 and 6 months after surgery	6 months
Secondary	Bone Mineral density	BMD adjacent to the acetabular cup during the follow up period, i.e. after 3, 6, 12 and 24 months	24 months
Secondary	Bone Mineral Density	BMD at the lumbar spine and at the contra lateral nonoperated hip 6, 12 and 24 months after surgery	24 months
Secondary	Standardised Uptake Value	Fluoride isotope uptake measured as SUV at the lumbar spine and at the contra lateral nonoperated hip after 3 and 6 months	6 months
Secondary	Biochemical markers for bone metabolism	biochemical markers for bone turnover and the relation to SUV and BMD findings at the proximal femur and acetabulum during the follow up period, i.e. 3, 6, 12 and 24 months after surgery	24 months
Secondary	Biochemical markers for bone metabolism in relation to Bone Mineral Density and Standardised Uptake Value	biochemical markers for bone turnover and the relation to SUV and BMD findings at anatomical sites not exposed to surgery, i.e. the lumbar spine and the contra lateral hip 3 and 6 months after surgery	24
Secondary	Biochemical markers for bone metabolism in relation to Bone Mineral Density and Standardised Uptake Value	to evaluate the natural course of an uncemented THA on BMD, i.e. the placebo group 3, 6, 12 and 24 months after surgery, SUV i.e. the placebo group 3 and 6 months after surgery and on biochemical markers, i.e. the placebo group 3, 6, 12 and 24 months after surgery	24
Secondary	Clinical outcome evaluation	to evaluate the patients Quality of Life, measured by Harris Hip score and EQ-5D questionnaires	24 months
Secondary	Adverse events	incidence and severity of adverse events (AEs) during the study period	24 months