Effects of Denosumab on Periprosthetic Bone After Total Hip Arthroplasty - Full Text View

Purpose

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.

Condition	Intervention	Phase
Osteoarthritis, Hip Ambulation Difficulty	Drug: denosumab	Phase 2

Study Type:	Interventional
Study Design:	Allocation: Randomized Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Caregiver, Investigator) Primary Purpose: Prevention
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

Resource links provided by NLM:

MedlinePlus related topics: Bone Density Minerals Osteoarthritis

Drug Information available for: Denosumab

U.S. FDA Resources

Further study details as provided by Uppsala University Hospital:

Primary Outcome Measures:

Bone Mineral Density [ Time Frame: 12 months ] [ Designated as safety issue: No ]
Bone mineral density by DXA in Gruen Zone 7 and a sum of Gruen zone 1-7

Secondary Outcome Measures:

Bone mineral Density [ Time Frame: 24 months ] [ Designated as safety issue: No ]
BMD, g/cm2, adjacent to the femur implant for Gruen Zone 1-7, 3, 6, and 24 months after surgery
Standardised Uptake value [ Time Frame: 6 months ] [ Designated as safety issue: No ]
fluoride isotope uptake, measured as (SUV), adjacent to the femoral stem, 3 and 6 months after surgery.
Standardised Uptake value [ Time Frame: 6 months ] [ Designated as safety issue: No ]
fluoride isotope uptake, measured as SUV adjacent to the acetabular cup 3 and 6 months after surgery
Bone Mineral density [ Time Frame: 24 months ] [ Designated as safety issue: No ]
BMD adjacent to the acetabular cup during the follow up period, i.e. after 3, 6, 12 and 24 months
Bone Mineral Density [ Time Frame: 24 months ] [ Designated as safety issue: No ]
BMD at the lumbar spine and at the contra lateral nonoperated hip 6, 12 and 24 months after surgery
Standardised Uptake Value [ Time Frame: 6 months ] [ Designated as safety issue: No ]
Fluoride isotope uptake measured as SUV at the lumbar spine and at the contra lateral nonoperated hip after 3 and 6 months
Biochemical markers for bone metabolism [ Time Frame: 24 months ] [ Designated as safety issue: No ]
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
Biochemical markers for bone metabolism in relation to Bone Mineral Density and Standardised Uptake Value [ Time Frame: 24 ] [ Designated as safety issue: No ]
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
Biochemical markers for bone metabolism in relation to Bone Mineral Density and Standardised Uptake Value [ Time Frame: 24 ] [ Designated as safety issue: No ]
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
Clinical outcome evaluation [ Time Frame: 24 months ] [ Designated as safety issue: No ]
to evaluate the patients Quality of Life, measured by Harris Hip score and EQ-5D questionnaires
Adverse events [ Time Frame: 24 months ] [ Designated as safety issue: No ]
incidence and severity of adverse events (AEs) during the study period

Estimated Enrollment:	64
Study Start Date:	March 2012
Estimated Study Completion Date:	July 2017
Estimated Primary Completion Date:	July 2016 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Active Comparator: Denosumab 1 ml (60 mg) subcutaneous injection Denosumab give in the posterior part of the upper arm after surgery followed by another injection 6 months later	Drug: denosumab Two doses of 60 mg in a solution of 1 ml, given as an subcutaneous injection with a 6 month interval Other Name: Prolia
Placebo Comparator: saline 1 ml subcutaneous injection 0.9% saline give in the posterior part of the upper arm after surgery followed by another injection 6 months later	Drug: denosumab Two doses of 60 mg in a solution of 1 ml, given as an subcutaneous injection with a 6 month interval Other Name: Prolia

Detailed 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.

Eligibility

Ages Eligible for Study:	35 Years to 65 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

male or female patient 35-65 years of age with an unilateral OAH requiring a THA and a healthy contralateral hip
body weight ≤110 kg or body mass index (BMI) ≤35 kg/m2
living in the Uppsala County
the eligible patients should have been given oral information, a written Patient Information and signed an Informed Consent

Exclusion Criteria:

on or previously have had bone-specific treatment, e.g. bisphosphonates, raloxifene, parathyroid hormone, strontium ranelate, during the last five years
patients on systemical corticosteroid for more than 3 months should not be considered
patients with diagnosed malignant disease during the last five years or known to have metastasis from malignant disease should be excluded
patients with compromised general conditions and an American Society of Anesthesiologists, ASA-score >31 should not be regarded eligible
patients with known drug or alcohol abuse or regarded as socially dysfunctional, as judged by the investigator, should not be considered for the study
pregnant women or women planning for pregnancy or fertile women (premenopausal) without contraceptives should not be accepted for the study
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.
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
any condition or laboratory findings which in the opinion of the Investigator makes the patient unsuitable for inclusion (for example claustrophobia)

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT01630941

Contacts

Contact: Hans Mallmin, MD PhD	+46186114478	hans.mallmin@akademiska.se
Contact: Nils Hailer, MD, PhD	+46186119038	nils.hailer@akademiska.se

Locations

Sweden
Department of Orthopedics	Recruiting
Uppsala, Sweden
Contact: Catharina Stromstedt catharina.stromstedt@akademiska.se
Principal Investigator: Hans Mallmin, MD, PhD
Sub-Investigator: Nils Hailer, MD, PhD
Sub-Investigator: Jan Milbrink, MD, PhD
Sub-Investigator: Demostenis Kiritopoulos, MD
Sub-Investigator: Andreas Nystrom, MD

Sponsors and Collaborators

Hans Mallmin

Investigators

Principal Investigator:	Hans Mallmin, MD, PhD	Uppsala University
Study Chair:	Nils Hailer, MD, PhD	Uppsala University

More Information

No publications provided

Responsible Party:	Hans Mallmin, MD, PhD, Uppsala University Hospital
ClinicalTrials.gov Identifier:	NCT01630941 History of Changes
Other Study ID Numbers:	2011-001481-18
Study First Received:	June 26, 2012
Last Updated:	June 27, 2012
Health Authority:	Sweden: Swedish National Council on Medical Ethics

Keywords provided by Uppsala University Hospital:

Osteoarthritis of the hip
Uncemented Total Hip Arthroplasty
DXA
BMD

PET
CT
Biochemical bone markers

Additional relevant MeSH terms:

Osteoarthritis
Osteoarthritis, Hip
Mobility Limitation
Arthritis

Joint Diseases
Musculoskeletal Diseases
Rheumatic Diseases
Signs and Symptoms

ClinicalTrials.gov processed this record on May 19, 2013