RA Denosumab on Bone Microstructure Study

This study is not yet open for participant recruitment. (see Contacts and Locations)
Verified January 2013 by Chinese University of Hong Kong
Sponsor:
Information provided by (Responsible Party):
Lai-Shan Tam, Chinese University of Hong Kong
ClinicalTrials.gov Identifier:
NCT01770106
First received: January 3, 2013
Last updated: January 15, 2013
Last verified: January 2013
  Purpose

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.


Condition Intervention Phase
Rheumatoid Arthritis
Drug: Denosumab
Drug: Alendronate
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Chinese University of Hong Kong:

Primary Outcome Measures:
  • Changes from baseline in bone volumetric density at distal radius at 6th month [ Time Frame: Baseline to 6th month ] [ Designated as safety issue: No ]
    Bone volumetric density is characterized by average volumetric bone mineral density (BMD) at distal radius by HR-pQCT


Secondary Outcome Measures:
  • Changes from baseline in trabecular bone microarchitecture at distal radius at 6th month [ Time Frame: Baseline to 6th month ] [ Designated as safety issue: No ]
    Trabecular bone microarchitecture is characterized by trabecular bone volume fraction (BV/TV) at distal radius by HR-pQCT

  • Changes from baseline in bone volumetric density at the 2nd metacarpal bone at 6th month [ Time Frame: Baseline to 6th month ] [ Designated as safety issue: No ]
    Volumetric bone density is characterized by average volumetric bone mineral density at the 2nd metacarpal bone measured by HR-pQCT

  • Changes from baseline in trabecular bone microarchitecture at 2nd metacarpal bone at 6th month [ Time Frame: Baseline to 6th month ] [ Designated as safety issue: No ]
    Trabecular bone microarchitecture is characterized by trabecular bone volume fraction (BV/TV) at 2nd metacarpal head by HR-pQCT

  • Changes from baseline in areal bone density at total hip at 6th month [ Time Frame: Baseline to 6th months ] [ Designated as safety issue: No ]
    Areal bone density at total hip is characterized by areal bone mineral density by DXA.

  • Changes from baseline in areal bone density at lumbar spine at 6th month [ Time Frame: Baseline to 6th month ] [ Designated as safety issue: No ]
    Areal bone density at lumbar spine is characterized by areal bone mineral denstiy at lumbar spine by DXA

  • Changes in areal bone density at distal radius at 6th month [ Time Frame: Baseline to 6th month ] [ Designated as safety issue: No ]
    Areal bone density is characterized by areal bone mineral density at distal radius by DXA

  • Changes from baseline in bone volumetric density at distal radius at 3rd month [ Time Frame: Baseline to 3rd month ] [ Designated as safety issue: No ]
    Bone volumetric density is characterized by average volumetric bone mineral density (BMD) at distal radius by HR-pQCT

  • Changes from baseline in trabecular bone microarchitecture at distal radius at 3rd month [ Time Frame: Baseline to 3rd month ] [ Designated as safety issue: No ]
    Trabecular bone microarchitecture is characterized by trabecular bone volume fraction (BV/TV) at distal radius by HR-pQCT

  • Changes from baseline in bone volumetric density at the 2nd metacarpal bone at 3rd month [ Time Frame: Baseline to 3rd month ] [ Designated as safety issue: No ]
    Volumetric bone density is characterized by average volumetric bone mineral density at the 2nd metacarpal bone measured by HR-pQCT

  • Changes from baseline in trabecular bone microarchitecture at 2nd metacarpal bone at 3rd month [ Time Frame: Baseline to 3rd month ] [ Designated as safety issue: No ]
    Trabecular bone microarchitecture is characterized by trabecular bone volume fraction (BV/TV) at 2nd metacarpal head by HR-pQCT

  • Changes from baseline in areal bone density at total hip at 3rd month [ Time Frame: Baseline to 3rd month ] [ Designated as safety issue: No ]
    Areal bone density at total hip is characterized by areal bone mineral density by DXA.

  • Changes from baseline in areal bone density at lumbar spine at 3rd month [ Time Frame: Baseline to 3rd month ] [ Designated as safety issue: No ]
    Areal bone density at lumbar spine is characterized by areal bone mineral denstiy at lumbar spine by DXA

  • Changes in areal bone density at distal radius at 3rd month [ Time Frame: Baseline to 3rd month ] [ Designated as safety issue: No ]
    Areal bone density is characterized by areal bone mineral density at distal radius by DXA


Estimated Enrollment: 40
Study Start Date: September 2013
Estimated Study Completion Date: December 2014
Estimated Primary Completion Date: September 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Denosumab
Patients in this arm will receive subcutaneous injection of denosumab 60mg every 6 months (1 dose for the study period).
Drug: Denosumab
Subcutaneous injection of denosumab 60mg every 6 months (1 dose for study period)
Other Name: Prolia®
Active Comparator: Standard treatment
Patients (n=20) in this arm will receive oral alendronate (Fosamax®)70mg once.
Drug: Alendronate
Alendronate 70mg once weekly
Other Name: Fosamax®

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

Ages Eligible for Study:   18 Years to 80 Years
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01770106

Contacts
Contact: Lai-Shan Tam, MD +852 26323128 lstam@cuhk.edu.hk

Locations
Hong Kong
Prince of Wales Hospital Not yet recruiting
Shatin, N.t., Hong Kong
Contact: Lai-Shan Tam, MD    +852 26323128    lstam@cuhk.edu.hk   
Principal Investigator: Lai-Shan Tam, MD         
Sponsors and Collaborators
Chinese University of Hong Kong
Investigators
Principal Investigator: Lai-Shan Tam, MD Chinese University of Hong Kong
  More Information

No publications provided

Responsible Party: Lai-Shan Tam, Professor, Chinese University of Hong Kong
ClinicalTrials.gov Identifier: NCT01770106     History of Changes
Other Study ID Numbers: RA-2011.510
Study First Received: January 3, 2013
Last Updated: January 15, 2013
Health Authority: Hong Kong: Joint CUHK-NTEC Clinical Research Ethics Committee

Keywords provided by Chinese University of Hong Kong:
Rheumatoid arthritis
Bone density
Bone microarchitecture
HR-pQCT

Additional relevant MeSH terms:
Arthritis
Arthritis, Rheumatoid
Joint Diseases
Musculoskeletal Diseases
Rheumatic Diseases
Connective Tissue Diseases
Autoimmune Diseases
Immune System Diseases
Alendronate
Bone Density Conservation Agents
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on August 01, 2014