ArthritisILANDNCT02498808
Interferon-lambda: Novel Biologics for Controlling Neutrophil-mediated Pathology in Rheumatic Diseases?
An observational study of Arthritis and Vasculitis, run by University of Oxford at 1 site in United Kingdom.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- Arthritis, Vasculitis
- How many people
- 85 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- Sep 2015to Dec 2018
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
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.
Who may be able to join
- 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
Who cannot join
- Unable to provide written informed consent
Trial locations and contacts
1 site in 1 country.
United Kingdom1 site, 1 recruiting
- Recruiting
Oxford University Hospitals NHS Foundation Trust
Oxford, OX3 7HE
Jana Vaskova
Raashid Luqmani, DM FRCP FRCPE
About this study
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).
Read the detailed description
Expression of Interferon lambda receptor 1 (IFNLR1)/interleukin 28 Receptor Alpha (IL28RA) in human neutrophils.
Neutrophils will be isolated from freshly drawn human blood with subsequent removal of red blood cells with dextran and/or magnetic-activated cell sorting (MACS). The investigators' preliminary results show that neutrophils isolated from the blood of a healthy donor express higher level of IL28RA messenger Ribonucleic Acid (mRNA) compared to Cluster of Differentiation-14 (CD14) negative or CD14 positive lymphocytes. To better understand the relative spread of IL28RA mRNA levels due to human heterogeneity, the investigators will compare the levels of IL28RA expression in neutrophils isolated from blood of 20 healthy donors. The investigators will examine whether treatment of human neutrophils ex vivo with recombinant human IL29 (Bristol- Meyers Squibb, BMS) induces Signal Transducer and Activators of Transcription 1 (STAT1) signalling. The investigators will also test newly generated antibodies to human IL28RA which have shown some specificity in IL28RA detection in cell lines, on neutrophil isolated from blood.
Expression of IFNLR1/IL28RA in neutrophils isolated from blood of rheumatic patients.
The investigators will then compare the levels of IL28RA expression on neutrophils isolated from blood of (1) 15 patients in the early phases of rheumatoid arthritis (RA) and while naïve to biologic therapeutic intervention; (2) 15 vasculitis patients with giant cell arteritis (GCA) (within one week of commencing high dose glucocorticoid) and (3) 15 vasculitis patients with granulomatosis with polyangitis (GPA; Wegener's) at presentation or during a relapse, prior to initiation of immunosuppressive therapy with either cyclophosphamide or rituximab. All patients will undergo standardised assessment of disease activity and damage, i.e. the Birmingham Vasculitis Activity Score version 3.0 (BVAS 3.0) and the Vasculitis Damage Index version 1.0 (VDI) for vasculitis or the disease activity score for 28 joints (DAS-28) for RA. This will allow the investigators to predict whether rheumatic patients are likely to respond to IL29 treatment.
Functional characterisation of human neutrophils treated with IL29.
The investigators will conduct a selective evaluation of the expression of adhesion molecules, the migratory responses and functional properties of human neutrophils treated with IL29 ex vivo. These selected activities will be examined in the IL29 treated neutrophils from blood of healthy donors, with or without stimulation with lipopolysaccharide (LPS), phorbol myristate acetate (PMA) or serum from RA and vasculitis patients. The investigators will assess the impact of IL29 treatment on neutrophils isolated from the blood of patients with RA and vasculitis.
- Conditions
- Arthritis, Vasculitis
- Keywords
- Interferon lambda, Interleukin-29, Neutrophil
- Medical subject headings
- Arthritis, Vasculitis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| 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 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Expression of IFNLR1/IL28Ra in human neutrophils, by laboratory measurement of blood neutrophils
This will be tested on samples of blood taken from patients
Measured: 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)
This will be assessed using the patient using the Birmingham Vasculitis Activity Score (version 3.0), a questionnaire completed by the clinician. A numeric score can be calculated (range 0-63)
Measured: 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)
This will be assessed using the Vasculitis Damage Index (Version 1.0), a questionnaire completed by the clinician. A numeric score can be calculated (0-64)
Measured: 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)
This will be assessed using a score of the number of painful and tender joints, results of the test of inflammatory markers (usually the C-reactive protein) and a patient's estimate of disease on a visual analogue scale. The data is recorded in a specifically designed calculator, providing a numerical score from 0 to 10
Measured: 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
This will be tested on samples of blood taken from patients.
Measured: Within one month of diagnosis (or flare of vasculitis)
STAT1 signalling by neutrophils
This will be tested on samples of blood taken from patients.
Measured: Within one month of diagnosis (or flare of vasculitis)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Jul 2015 (estimated)
- Study startSep 2015
- Primary completionAug 2018 (estimated)
- Study completionDec 2018 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for ArthritisStudies of the same condition, open and under way.
- More trials run by University of OxfordThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Case-control
- Time perspective
- Prospective
- Enrolment
- 85 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Oxford
- Sponsor type
- University, hospital or other
- Collaborators
- Arthritis Research UK
- Responsible party
- Principal investigator, Raashid Luqmani, University of Oxford
- Investigators
- Raashid A Luqmani, DM FRCP, Principal investigator, Professor of Rheumatology
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02498808
- Sponsor's protocol ID
- 20892
- Acronym
- ILAND
- Status last verified
- Aug 2017
- First submitted
- 10 Jul 2015
- Last updated
- 2 Aug 2017
- Results posted
- No
- Data monitoring committee
- No
Publications
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.
PubMed 25941255Kotenko 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.
PubMed 12483210Sheppard 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.
PubMed 12469119
Study at a glance
From the registry record, last updated by the sponsor on 2 Aug 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Interferon-lambda: Novel Biologics for Controlling Neutrophil-mediated Pathology in Rheumatic Diseases?
- ClinicalTrials.gov ID
- NCT02498808
- Acronym / sponsor ID
- ILAND / 20892
- Conditions
- Arthritis, Vasculitis
- Keywords
- Interferon lambda, Interleukin-29, Neutrophil
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 85 participants (estimated)
- Lead sponsor
- University of OxfordUniversity, hospital or other
- Collaborators
- Arthritis Research UK
- Study start
- Sep 2015 (actual)
- Primary completion
- Aug 2018 (estimated)
- Study completion
- Dec 2018 (estimated)
- First posted
- 15 Jul 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
Detailed description
Expression of Interferon lambda receptor 1 (IFNLR1)/interleukin 28 Receptor Alpha (IL28RA) in human neutrophils.
Neutrophils will be isolated from freshly drawn human blood with subsequent removal of red blood cells with dextran and/or magnetic-activated cell sorting (MACS). The investigators' preliminary results show that neutrophils isolated from the blood of a healthy donor express higher level of IL28RA messenger Ribonucleic Acid (mRNA) compared to Cluster of Differentiation-14 (CD14) negative or CD14 positive lymphocytes. To better understand the relative spread of IL28RA mRNA levels due to human heterogeneity, the investigators will compare the levels of IL28RA expression in neutrophils isolated from blood of 20 healthy donors. The investigators will examine whether treatment of human neutrophils ex vivo with recombinant human IL29 (Bristol- Meyers Squibb, BMS) induces Signal Transducer and Activators of Transcription 1 (STAT1) signalling. The investigators will also test newly generated antibodies to human IL28RA which have shown some specificity in IL28RA detection in cell lines, on neutrophil isolated from blood.
Expression of IFNLR1/IL28RA in neutrophils isolated from blood of rheumatic patients.
The investigators will then compare the levels of IL28RA expression on neutrophils isolated from blood of (1) 15 patients in the early phases of rheumatoid arthritis (RA) and while naïve to biologic therapeutic intervention; (2) 15 vasculitis patients with giant cell arteritis (GCA) (within one week of commencing high dose glucocorticoid) and (3) 15 vasculitis patients with granulomatosis with polyangitis (GPA; Wegener's) at presentation or during a relapse, prior to initiation of immunosuppressive therapy with either cyclophosphamide or rituximab. All patients will undergo standardised assessment of disease activity and damage, i.e. the Birmingham Vasculitis Activity Score version 3.0 (BVAS 3.0) and the Vasculitis Damage Index version 1.0 (VDI) for vasculitis or the disease activity score for 28 joints (DAS-28) for RA. This will allow the investigators to predict whether rheumatic patients are likely to respond to IL29 treatment.
Functional characterisation of human neutrophils treated with IL29.
The investigators will conduct a selective evaluation of the expression of adhesion molecules, the migratory responses and functional properties of human neutrophils treated with IL29 ex vivo. These selected activities will be examined in the IL29 treated neutrophils from blood of healthy donors, with or without stimulation with lipopolysaccharide (LPS), phorbol myristate acetate (PMA) or serum from RA and vasculitis patients. The investigators will assess the impact of IL29 treatment on neutrophils isolated from the blood of patients with RA and vasculitis.
Study design
- Observational model
- Case-control
- Time perspective
- Prospective
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| 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 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
- 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.
Key inclusion criteria (5 listed)
- 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
Key exclusion criteria (1 listed)
- Unable to provide written informed consent
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Expression of IFNLR1/IL28Ra in human neutrophils, by laboratory measurement of blood neutrophils
Time frame: Within one month of diagnosis (or flare of vasculitis)
This will be tested on samples of blood taken from patients
5 secondary outcomes
Vasculitis disease activity, based on a scale of disease activity in vasculitis (Birmingham Vasculitis Activity Score version 3.0, BVAS 3.0)
Time frame: 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)
Time frame: 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)
Time frame: 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
Time frame: Within one month of diagnosis (or flare of vasculitis)
STAT1 signalling by neutrophils
Time frame: Within one month of diagnosis (or flare of vasculitis)
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Aug 2017.
- Background: PubMed 25941255Blazek 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.
- Background: PubMed 12483210Kotenko 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.
- Background: PubMed 12469119Sheppard 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Raashid A Luqmani, DM FRCP principal investigator
Professor of Rheumatology
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Arthritis and Vasculitis, run by University of Oxford at 1 site in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 2 Aug 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Raashid A Luqmani, DM FRCP (01865227971, jana.vaskova@ndorms.ox.ac.uk), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Expression of IFNLR1/IL28Ra in human neutrophils, by laboratory measurement of blood neutrophils (time frame: Within one month of diagnosis (or flare of vasculitis)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02498808, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Aug 2017.