Ignite Creation Date:
2024-05-06 @ 12:12 PM
Last Modification Date:
2024-10-26 @ 12:55 PM
Study NCT ID:
NCT03701789
Status:
UNKNOWN
Last Update Posted:
2021-01-15
First Post:
2018-10-04
Brief Title:
Effect of Baricitinib Treatment on Peripheral Bone in RA
Sponsor:
University of Erlangen-Nürnberg Medical School
Organization:
University of Erlangen-Nürnberg Medical School
Study Overview
Official Title:
Evaluation of Bone Quality in Patients With Rheumatoid Arthritis Treated With Baricitinib Single Centre Mode of Action Study BARE BONE
Status:
UNKNOWN
Status Verified Date:
2021-01
Last Known Status:
ACTIVE_NOT_RECRUITING
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
BAREBONE
Brief Summary:
Patients with Rheumatoid Arthritis RA suffer systemic and peripheral bone loss In this study we aim to test the efficacy of in-label treatment with Baricitinib on the volumetric bone mineral density in patients with RA over 52 weeks Inclusion of RA patients comprises pathologic volumetric bone mineral density measured by High Resolution peripheral quantitative Computed Tomomgraphy HR-pQCT maging of finger joints
Detailed Description:
Systemic and local bone loss is a pathognomonic feature of rheumatoid arthritis and can be seen in a very early phase of the disease Understanding the pathogenesis of rheumatoid arthritis RA has advanced substantially in recent years The mode of action of immunosuppressive medication on pro-inflammatory cytokines different cell types or activation of cells is intensively studied and understood In contrary little is known on how these medications influence bone damage in peripheral joints in terms of bone density bone microstructure bone quality or erosions This is due to different reasons One factor is the lack of suitable user-independent imaging tools for outcome measurements For example using conventional X-ray of the hand and fingers no information can be obtained about the volumetric density microarchitecture bone quality or volumetric erosion size Applying Dual-energy Xray absorptiometry DXA of peripheral joints does also not provide information about the volumetric bone density and no accurate difference can be obtained regarding cortical or trabecular density parameters Magnetic Resonance Imaging MRI as an outcome measure in RA enables good the detection and partly quantification of erosions however no information about bone density can be quantified HR-pQCT high resolution peripheral quantitative computed tomography imaging allows in detail 82 micrometer isotropic voxelsize evaluation of density microstructure parameters as well as quantification of erosions in peripheral joints Furthermore HR-pQCT data allows the biomechanical analysis of the bone and therefore statements on the bone quality can be made
Modulating inhibitors targeting the Janus Kinase JAK - Signal Transducer and Activator of Transcription STAT pathway effect pro-inflammatory cytokines and have been approved for therapy in RA patients Analysis of the inhibition of the JAK-STAT pathway in rheumatoid arthritis synovium showed decreased phosphorylation of STAT1 Also pro-inflammatory activation of STAT1 and downstream targets were inhibited by JAK inhibition More interesting STAT1-- mice have higher bone density due to Runx2 activation but are otherwise are indistinguishable from wildtype mice Furthermore inhibition of STAT1 accelerates bone repair after trauma a similar process in our observation in rheumatoid arthritis joints On the other hand JAK1 deficient mice showed reduced body mass peri-natal which has been speculated to indicate bone growth delays Focusing on bone loss JAK inhibition tofacitinib suppressed osteoclast mediated bone destruction via reduction of T cell derived RANKL In vitro we observed that osteoclast OC differentiation was not influenced by JAK inhibition in regard to OC numbers and transcription factor expression Interestingly in osteoblast cultures JAK inhibition induced Runx2 Col1a and Osterix In co-culture assays with osteoblasts and OC precursors JAK inhibition led to decreased OC differentiationThus JAK inhibition mediated OC function is not only influenced by T cell but also osteoblast derived RANKL and therefore interferes in the balance of bone turnover by activating osteoblastsUsing HR-pQCT measurements of fingers of RA patients treated with tofacitinib in a small sample size we detected an astonishing gain of volumetric bone mineral density mg Hydroxylapatitemm³ Furthermore we noticed a decrease of the intra-articular cortical porosity and a positive change of erosion size In these cases volumetric bone density in metacarpal joints improved up to 20 In our experience regarding other immunosuppressive medication for example anti-TNF Inhibition no comparable effect was observed
The longitudinal setup of this mode of action study is used to determine the effect of baricitinib on the change of the volumetric bone mineral density in RA patients with pathologic vBMD measured by HR-pQCT technique over 52 weeks
Modulating inhibitors targeting the Janus Kinase JAK - Signal Transducer and Activator of Transcription STAT pathway effect pro-inflammatory cytokines and have been approved for therapy in RA patients Analysis of the inhibition of the JAK-STAT pathway in rheumatoid arthritis synovium showed decreased phosphorylation of STAT1 Also pro-inflammatory activation of STAT1 and downstream targets were inhibited by JAK inhibition More interesting STAT1-- mice have higher bone density due to Runx2 activation but are otherwise are indistinguishable from wildtype mice Furthermore inhibition of STAT1 accelerates bone repair after trauma a similar process in our observation in rheumatoid arthritis joints On the other hand JAK1 deficient mice showed reduced body mass peri-natal which has been speculated to indicate bone growth delays Focusing on bone loss JAK inhibition tofacitinib suppressed osteoclast mediated bone destruction via reduction of T cell derived RANKL In vitro we observed that osteoclast OC differentiation was not influenced by JAK inhibition in regard to OC numbers and transcription factor expression Interestingly in osteoblast cultures JAK inhibition induced Runx2 Col1a and Osterix In co-culture assays with osteoblasts and OC precursors JAK inhibition led to decreased OC differentiationThus JAK inhibition mediated OC function is not only influenced by T cell but also osteoblast derived RANKL and therefore interferes in the balance of bone turnover by activating osteoblastsUsing HR-pQCT measurements of fingers of RA patients treated with tofacitinib in a small sample size we detected an astonishing gain of volumetric bone mineral density mg Hydroxylapatitemm³ Furthermore we noticed a decrease of the intra-articular cortical porosity and a positive change of erosion size In these cases volumetric bone density in metacarpal joints improved up to 20 In our experience regarding other immunosuppressive medication for example anti-TNF Inhibition no comparable effect was observed
The longitudinal setup of this mode of action study is used to determine the effect of baricitinib on the change of the volumetric bone mineral density in RA patients with pathologic vBMD measured by HR-pQCT technique over 52 weeks
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
False
Is an FDA AA801 Violation?:
None