NCT02498808

Brief Summary

Neutrophils emerge as key immune cells in the initiation and perpetuation of immune responses in autoimmune diseases. They display marked abnormalities in phenotype and function in various autoimmune diseases, including systemic vasculitis, systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). These neutrophils are characterised by an extended life span, increased capacity to produce reactive oxygen species, active gene expression and release of extracellular traps. Consequently, there is a need for better understanding of neutrophil phenotype and functions in these conditions, as well as for identifying molecules capable of specifically manipulating neutrophil function. The investigators have recently discovered that interferon lambdas (IFN-λs), also known as interleukin 28 (IL28) and interleukin 29 (IL29), class II cytokines with previously studied anti-viral biological functions, specifically suppress neutrophil infiltration and interleukin-1β production and thereby, halt and reverse the development of collagen induced arthritis (CIA). The investigators propose to further investigate the cellular and molecular mechanisms behind this suppression and examine the translational potential of the investigators' finding by examining the IFN-λ receptor expression and function in neutrophils isolated from the blood of healthy donors and rheumatic patients (early rheumatoid arthritis and vasculitis).

Trial Health

43
At Risk

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Trial has exceeded expected completion date
Enrollment
85

participants targeted

Target at P50-P75 for all trials

Timeline
Completed

Started Sep 2015

Typical duration for all trials

Geographic Reach
1 country

1 active site

Status
unknown

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

July 10, 2015

Completed
5 days until next milestone

First Posted

Study publicly available on registry

July 15, 2015

Completed
2 months until next milestone

Study Start

First participant enrolled

September 1, 2015

Completed
2.9 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

August 1, 2018

Completed
4 months until next milestone

Study Completion

Last participant's last visit for all outcomes

December 1, 2018

Completed
Last Updated

August 2, 2017

Status Verified

August 1, 2017

Enrollment Period

2.9 years

First QC Date

July 10, 2015

Last Update Submit

August 1, 2017

Conditions

ArthritisVasculitis

Keywords

Interferon lambdaInterleukin-29Neutrophil

Outcome Measures

Primary Outcomes (1)

  • Expression of IFNLR1/IL28Ra in human neutrophils, by laboratory measurement of blood neutrophils

    This will be tested on samples of blood taken from patients

    Within one month of diagnosis (or flare of vasculitis)

Secondary Outcomes (5)

  • Vasculitis disease activity, based on a scale of disease activity in vasculitis (Birmingham Vasculitis Activity Score version 3.0, BVAS 3.0)

    Within one month of diagnosis (or flare of vasculitis)

  • Vasculitis damage, based on a scale of disease damage in vasculitis (Vasculitis Damage Index version 1.0, VDI 1.0)

    Within one month of diagnosis (or flare of vasculitis)

  • Disease activity assessment score for arthritis, based on a scale (Disease activity score for 28 joints, DAS-28)

    Within one month of diagnosis (or flare of vasculitis)

  • Expression of Toll like receptors, adhesion molecules and chemokine receptors in human neutrophils, by laboratory measurement of blood neutrophils

    Within one month of diagnosis (or flare of vasculitis)

  • STAT1 signalling by neutrophils

    Within one month of diagnosis (or flare of vasculitis)

Study Arms (4)

Healthy controls

Staff or patients attending hospital or visitors attending with patients. They should not have vasculitis or inflammatory arthritis

Early rheumatoid arthritis

Newly diagnosed patients with rheumatoid arthritis attending hospital, prior to use of biologic therapies

New or relapsing ANCA vasculitis

Newly diagnosed or flaring patients with anti-neutrophil cytoplasm antibody associated systemic vasculitis attending hospital

Newly diagnosed giant cell arteritis

Newly diagnosed patients with giant cell arteritis attending hospital

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersYes
Age GroupsAdult (18-64), Older Adult (65+)
Sampling MethodNon-Probability Sample
Study Population

Healthy volunteers will be recruited as staff or patients attending secondary care or accompanying patients but who do not have vasculitis or any form of inflammatory arthritis Patients with vasculitis or arthritis who are attending secondary care will be invited to participate if they fulfill eligibility criteria.

You may qualify if:

  • Healthy volunteer or
  • Recent diagnosis of rheumatoid arthritis within 1 month or
  • New diagnosis of giant cell arteritis within 1 month or
  • New diagnosis of anti-neutrophil cytoplasm antibody associated vasculitis within 1 month or
  • Flare of anti-neutrophil cytoplasm antibody associated vasculitis within one month

You may not qualify if:

  • Unable to provide written informed consent

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Oxford University Hospitals NHS Foundation Trust

Oxford, OX3 7HE, United Kingdom

RECRUITING

Related Publications (3)

  • Blazek K, Eames HL, Weiss M, Byrne AJ, Perocheau D, Pease JE, Doyle S, McCann F, Williams RO, Udalova IA. IFN-lambda resolves inflammation via suppression of neutrophil infiltration and IL-1beta production. J Exp Med. 2015 Jun 1;212(6):845-53. doi: 10.1084/jem.20140995. Epub 2015 May 4.

    PMID: 25941255BACKGROUND

  • Kotenko SV, Gallagher G, Baurin VV, Lewis-Antes A, Shen M, Shah NK, Langer JA, Sheikh F, Dickensheets H, Donnelly RP. IFN-lambdas mediate antiviral protection through a distinct class II cytokine receptor complex. Nat Immunol. 2003 Jan;4(1):69-77. doi: 10.1038/ni875. Epub 2002 Dec 16.

    PMID: 12483210BACKGROUND

  • Sheppard P, Kindsvogel W, Xu W, Henderson K, Schlutsmeyer S, Whitmore TE, Kuestner R, Garrigues U, Birks C, Roraback J, Ostrander C, Dong D, Shin J, Presnell S, Fox B, Haldeman B, Cooper E, Taft D, Gilbert T, Grant FJ, Tackett M, Krivan W, McKnight G, Clegg C, Foster D, Klucher KM. IL-28, IL-29 and their class II cytokine receptor IL-28R. Nat Immunol. 2003 Jan;4(1):63-8. doi: 10.1038/ni873. Epub 2002 Dec 2.

    PMID: 12469119BACKGROUND

Biospecimen

Retention: SAMPLES WITH DNA

Blood samples

MeSH Terms

Conditions

ArthritisVasculitis

Condition Hierarchy (Ancestors)

Joint DiseasesMusculoskeletal DiseasesVascular DiseasesCardiovascular Diseases

Study Officials

  • Raashid A Luqmani, DM FRCP

    Professor of Rheumatology

    PRINCIPAL INVESTIGATOR

Central Study Contacts

Raashid A Luqmani, DM FRCP

CONTACT

01865227971jana.vaskova@ndorms.ox.ac.uk

Jana Vaskova

CONTACT

01865227971jana.vaskova@ndorms.ox.ac.uk

Study Design

Study Type
observational
Observational Model
CASE CONTROL
Time Perspective
PROSPECTIVE
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Professor of Rheumatology

Study Record Dates

First Submitted

July 10, 2015

First Posted

July 15, 2015

Study Start

September 1, 2015

Primary Completion

August 1, 2018

Study Completion

December 1, 2018

Last Updated

August 2, 2017

Record last verified: 2017-08

Locations

GB(1)