RA Denosumab on Bone Microstructure Study

NCT ID: NCT01770106

Last Updated: 2014-09-11

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 40 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-12-31
• Study Completion Date: 2014-06-30

Brief 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.

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.

Conditions

Rheumatoid Arthritis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Denosumab

Patients in this arm will receive subcutaneous injection of denosumab 60mg every 6 months (1 dose for the study period).

Group Type: EXPERIMENTAL

Denosumab

Intervention Type: DRUG

Subcutaneous injection of denosumab 60mg every 6 months (1 dose for study period)

Standard treatment

Patients (n=20) in this arm will receive oral alendronate (Fosamax®)70mg once.

Group Type: ACTIVE_COMPARATOR

Alendronate

Intervention Type: DRUG

Alendronate 70mg once weekly

Interventions

Denosumab

Subcutaneous injection of denosumab 60mg every 6 months (1 dose for study period)

Intervention Type: DRUG

Alendronate

Alendronate 70mg once weekly

Intervention Type: DRUG

Other Intervention Names

Prolia®; Fosamax®

Eligibility 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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Chinese University of Hong Kong

OTHER

Sponsor Role: lead

Responsible Party

Lai-Shan Tam

Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Lai-Shan Tam, MD

Role: PRINCIPAL_INVESTIGATOR

Chinese University of Hong Kong

Locations

Prince of Wales Hospital

Shatin, N.t., Hong Kong

Countries

Hong Kong

References

Yue J, Griffith JF, Xiao F, Shi L, Wang D, Shen J, Wong P, Li EK, Li M, Li TK, Zhu TY, Hung VW, Qin L, Tam LS. Repair of Bone Erosion in Rheumatoid Arthritis by Denosumab: A High-Resolution Peripheral Quantitative Computed Tomography Study. Arthritis Care Res (Hoboken). 2017 Aug;69(8):1156-1163. doi: 10.1002/acr.23133. Epub 2017 Jul 10.

Reference Type: DERIVED

PMID: 27768831 (View on PubMed)

Other Identifiers

RA-2011.510

Identifier Type: -

Identifier Source: org_study_id