RA Denosumab on Bone Microstructure Study
Information source: Chinese University of Hong Kong
ClinicalTrials.gov processed this data on August 23, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Rheumatoid Arthritis
Intervention: Denosumab (Drug); Alendronate (Drug)
Phase: Phase 4
Status: Completed
Sponsored by: Chinese University of Hong Kong Official(s) and/or principal investigator(s): Lai-Shan Tam, MD, Principal Investigator, Affiliation: Chinese University of Hong Kong
Summary
The aim of this study is to compare the effects of denosumab and a current standard
treatment on cortical and trabecular microarchitecture at the radius and second metacarpal
in rheumatoid arthritis (RA) patients with low bone mineral density using high resolution
peripheral quantitative computed tomography (HR-pQCT) during a 6-month open-label randomized
controlled study. Forty ambulatory Chinese females, who consent to receive alendronate as
standard treatment subjective to the randomization, will be enrolled in this study. Subjects
will be randomized to 2 arms receiving: 1) subcutaneous injection of denosumab 60mg
(Prolia®) every 6 months (n=20), or 2) oral alendronate weekly (Fosamax® once weekly 70 mg,
n=20). In addition, all patients will be given a daily calcium supplement (1500mg caltrate
/day) and 1 multivitamin tablet per day. Efficacy and safety assessment will be performed at
baseline, month 3 and month 6. aBMD of lumbar spine, total hip and non-dominant distal
radius will be measured using dual-energy X-ray absorptiometry (DXA) and microarchitecture
of bone is measured at the non-dominant distal radius and the second metacarpal bone of the
non-dominant hand using HR-pQCT.
Clinical Details
Official title: Comparison of the Effect of Denosumab and Alendronate on Bone Density and Microarchitecture in Rheumatoid Arthritis Females With Low Bone Mass: A Randomized Controlled Trial
Study design: Allocation: Randomized, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Primary outcome: Changes from baseline in bone volumetric density at distal radius at 6th month
Secondary outcome: Changes from baseline in trabecular bone microarchitecture at distal radius at 6th monthChanges from baseline in bone volumetric density at the 2nd metacarpal bone at 6th month Changes from baseline in trabecular bone microarchitecture at 2nd metacarpal bone at 6th month Changes from baseline in areal bone density at total hip at 6th month Changes from baseline in areal bone density at lumbar spine at 6th month Changes in areal bone density at distal radius at 6th month Changes from baseline in bone volumetric density at distal radius at 3rd month Changes from baseline in trabecular bone microarchitecture at distal radius at 3rd month Changes from baseline in bone volumetric density at the 2nd metacarpal bone at 3rd month Changes from baseline in trabecular bone microarchitecture at 2nd metacarpal bone at 3rd month Changes from baseline in areal bone density at total hip at 3rd month Changes from baseline in areal bone density at lumbar spine at 3rd month Changes in areal bone density at distal radius at 3rd month
Detailed description:
Rheumatoid arthritis (RA) is a chronic, systemic inflammatory disease most typical in women.
Generalized osteoporosis is common in RA, at axial and appendicular skeleton and in females
and males. Denosumab is a fully humanized IgG monoclonal antibody that targets the receptor
activator of nuclear factor κB ligand (RANKL). Denosumab prevents the binding and activation
of the RANK receptors on the osteoclasts and hence inhibits osteoclasts formation,
activation, function and survival. Denosumab results in more rapid and greater reductions in
bone remodeling and correspondingly greater increases in areal bone mineral density (aBMD)
at all skeletal sites. Denosumab was approved by FDA in June 2010 for the treatment of
postmenopausal women with osteoporosis at high risk of fracture. Denosumab (Prolia®) is also
licensed in Hong Kong.
A high-resolution peripheral quantitative computed tomography (HR-pQCT) capable of achieving
an isotropic voxel size of 80μm at tolerable radiation doses (3μSv) is available for the
assessment of trabecular and cortical microarchitecture at the distal radius and tibia. This
technique bears excellent precision for both density and microstructure measures.
Denosumab's greater potency in suppressing bone remodeling and greater effect on areal BMD
than alendronate, particularly at predominantly cortical sites such as the distal third of
the radius, may reflect the differing mechanism of action of these drugs, which, in turn,
influence bone microarchitecture.
The aim of this study is to compare the effects of denosumab and a current standard
treatment on cortical and trabecular microarchitecture at the radius and second metacarpal
in RA patients with low bone mineral density using HR-pQCT during a 6-month open-label
randomized controlled study. One bisphosphonate, namely alendronate sodium (or alendronate)
is chosen to generate a heterogeneous and comparable active control group. This is a 6-month
open-label randomized controlled clinical trial. Forty ambulatory Chinese females, who
consent to receive alendronate as standard treatment subjective to the randomization, will
be enrolled from the rheumatology clinic of the Prince of Wales Hospital in this study.
Subjects will be randomized to 2 groups receiving: 1) subcutaneous injection of denosumab
60mg (Prolia®) every 6 months (n=20), or 2) a standard treatment: oral alendronate weekly
(Fosamax® once weekly 70 mg, n=20). In addition, all patients will be given a daily calcium
supplement (1500mg caltrate /day) and 1 multivitamin tablet per day. Efficacy and safety
assessment will be performed at baseline, month 3 and month 6. aBMD of lumbar spine, total
hip and non-dominant distal radius will be measured using dual-energy X-ray absorptiometry
(DXA) and microarchitecture of bone is measured at the non-dominant distal radius and the
second metacarpal bone of the non-dominant hand using HR-pQCT.
Eligibility
Minimum age: 18 Years.
Maximum age: 80 Years.
Gender(s): Female.
Criteria:
Inclusion Criteria:
- with a diagnosis of RA according to the 2010 new 2010 American College of
Rheumatology/ European League Against Rheumatism classification criteria
- at an age over 18 years old
- have a lumbar spine, or total hip or distal radius T-score lower than -1. 5 by DXA
- without severe deformity in metacarpophalangeal (MCP) joints which would influence
the longitudinal assessment of HR-pQCT
- consent to receive alendronate if randomized to standard treatment group.
Exclusion Criteria:
- they have previous use of denosumab, teriparatide, alendronate or other
anti-resorptive agents;
- they have a history of recent major gastrointestinal (GI) tract disease (e. g.
oesophagitis or GI ulceration) or have experienced any previous adverse reaction to
bisphosphonate therapy;
- they are receiving other bone-active drugs, such as hormonal replacement therapy,
thyroxine, thiazide and diuretics;
- they have conditions affecting bone metabolism; contraindications to alendronate and
denosumab (uncorrected hypocalcemia);
- they have unexplained hypocalcemia;
- they have severe renal impairment or serum creatinine level of >200umol/L;
- they are pregnant or breastfeeding;
- they do not understand Chinese or are incompetent in giving consent.
Locations and Contacts
Prince of Wales Hospital, Shatin, N.t., Hong Kong
Additional Information
Starting date: December 2012
Last updated: September 10, 2014
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