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Trial record 9 of 62 for:    Baricitinib

Effect of Baricitinib Treatment on Peripheral Bone in RA (BAREBONE)

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ClinicalTrials.gov Identifier: NCT03701789
Recruitment Status : Recruiting
First Posted : October 10, 2018
Last Update Posted : October 8, 2019
Sponsor:
Information provided by (Responsible Party):
University of Erlangen-Nürnberg Medical School

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.

Condition or disease Intervention/treatment Phase
Rheumatoid Arthritis Bone Density Finger Joints Drug: Baricitinib Phase 3

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 differentiation.Thus 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 osteoblasts.Using 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 Hydroxylapatite/mm³). 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.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 15 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Other
Official Title: Evaluation of Bone Quality in Patients With Rheumatoid Arthritis Treated With Baricitinib: Single Centre, Mode of Action Study (BARE BONE)
Actual Study Start Date : September 11, 2018
Estimated Primary Completion Date : September 11, 2020
Estimated Study Completion Date : September 11, 2020

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Patients with Rheumatoid Arthritis
In-label treatment with Baricitinib
Drug: Baricitinib
Effect of Baricitinib on vBMD measured by HR-pQCT
Other Name: Oliumiant




Primary Outcome Measures :
  1. Change in volumetric bone mineral density (vBMD) in metacarpal and radial bone between baseline and week 52 in patients with rheumatoid arthritis treated with baricitinib as determined by HR-pQCT [ Time Frame: 52 weeks ]
    HR-pQCT



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 74 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Main inclusion criteria:

Patients eligible for inclusion in this study have to fulfil all of the following criteria:

  • Subject must be able to understand and communicate with the investigator and comply with the requirements of the study, must give a written and signed and dated informed consent before any study assessment is performed
  • Male or non-pregnant, non-lactating female subjects aged between 18 - 74
  • Women of childbearing potential must oblige to use a highly effective method of birth control until at least 4 weeks after the last IMP administration
  • Diagnosis of RA according to the ACR/EULAR criteria and with symptoms for at least 3 months with moderate to severe RA
  • pathologic volumetric bone density, microstructure or presence of erosions detected by HR-pQCT and or MRI measurement
  • Previous treatment with at least one DMARD (e.g. methotrexate) without sufficient clinical response or stopped due to toxicities
  • Fulfil criteria for baricitinib treatment according to its SmPC

Exclusion Criteria:

  • Ongoing pregnancy status or breast-feeding

    • Chest X-ray or chest MRI with evidence of ongoing infectious or malignant process, obtained within 3 months or according to local guidelines, prior to screening and evaluated by a qualified physician
    • Contraindication for baricitinib treatment according to its SmPC
    • Current treatment with bDMARDs or other JAK-inhibitors
    • Creatinine clearance < 60ml/min (calculated analogue MDRD)
    • Current treatment with OAT3 inhibitors
    • History or evidence of ongoing alcohol or drug abuse, within the last six months before inclusion
    • Participation in an interventional clinical trial with an IMP within the last 4 weeks

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03701789


Contacts
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Contact: Arnd Kleyer, MD 0049 9131 84 32093 arnd.kleyer@uk-erlangen.de
Contact: Sara Bayat, MD 0049 9131 85 43016 sara.bayat@uk-erlangen.de

Locations
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Germany
Universitiy Hospital Erlangen Recruiting
Erlangen, Bavaria, Germany, 91052
Contact: Arnd Kleyer, MD    0049 9131 85 32093    arnd.kleyer@uk-erlangen.de   
Contact: Sara Bayat, MD    0049 9131 85 43016    sara.bayat@uk-erlangen.de   
Sponsors and Collaborators
University of Erlangen-Nürnberg Medical School
Investigators
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Principal Investigator: Arnd Kleyer, MD Department of Internal Medicine 3, Rheumatology and Immunology Universital Hospital Erlangen

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Responsible Party: University of Erlangen-Nürnberg Medical School
ClinicalTrials.gov Identifier: NCT03701789     History of Changes
Other Study ID Numbers: BAREBONE2018
First Posted: October 10, 2018    Key Record Dates
Last Update Posted: October 8, 2019
Last Verified: October 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Additional relevant MeSH terms:
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Arthritis
Arthritis, Rheumatoid
Joint Diseases
Musculoskeletal Diseases
Rheumatic Diseases
Connective Tissue Diseases
Autoimmune Diseases
Immune System Diseases