Rheumatoid ArthritisTHERAPISTNCT02620189
Th17 Responses Evaluated in RA Patients on Inhibitors of TNFα
An observational study of Rheumatoid Arthritis, run by Queen Mary University of London at 8 sites in United Kingdom.
Trial summary
Preliminary data suggest that up-regulation of Interleukin -17 (IL-17) and the T-helper 17 (Th17) pathway occurs in rheumatoid arthritis (RA) patients on anti-Tumour Necrosis Factor (TNF) therapy who demonstrated an incomplete clinical response. Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- Rheumatoid Arthritis
- What is being tested?
- Anti-TNF Biologics Therapy
- How many people
- 60 participants
- Where
- 8 sitesUnited Kingdom
- Study dates
- Mar 2015to 24 May 2017
- 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: Subjects who fulfil the NICE guidelines for biologic anti-TNF therapy as their first line treatment following failure of standard disease modifying anti-rheumatic therapy will be recruited from various secondary care settings at a number of centres throughout the UK.
Who may be able to join
- Men and women ≥ 18 years of age
- An RA diagnosis as defined by the 2010 revised EULAR/ACR classification criteria.
- Subjects who fulfil the NICE guidelines for Biologic therapy as their first line treatment following failure of standard disease modifying anti-rheumatic therapy.
- Subjects may be on cDMARDs (or MTX monotherapy) one of which must be MTX. Participants should be receiving MTX for at least 2 months at a stable dose of 7.5-25 mg/week before Week 0 visit.
- Subjects may be on oral steroids (prednisone ≤10 mg/day, or equivalent corticosteroid) with a stable dose for the 4 weeks prior to Week 0 visit.
- Men and women of childbearing potential must use adequate birth control measures (e.g., abstinence, oral contraceptives, intrauterine device, barrier method with spermicide, or surgical sterilization) for the duration of the study.
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- Participants must be able to adhere to the study visit schedule.
- The participant must be capable of giving informed consent and the consent must be obtained prior to any screening procedures.
- Must have a chest X-ray within 6 months prior to commencement of anti-TNF therapy with no evidence of malignancy, infection or fibrosis.
Who cannot join
- Participants will be excluded from this study for any of the following reasons:
- Women who are pregnant or breast feeding.
- Previous use of Rheumatoid Arthritis anti-TNF biologics, or ANY other type of biologic therapy or Investigational Medicinal Product.
- Treatment with any other therapeutic agent targeted at reducing TNF within 3 months of screening.
- Serious infections (such as pneumonia or pyelonephritis) in the previous 3 months. Less serious infections (such as acute upper respiratory tract infection [colds] or simple urinary tract infection) need not be considered exclusions at the discretion of the investigator.
- Known HIV, Hepatitis B, or Hepatitis C infection.
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- Have active TB or have evidence of latent TB (old or latent TB on chest x-ray, without adequate therapy for TB initiated prior to first dose of study drug). Participants with a current close contact with an individual with active TB and participants who have completed treatment for active TB within the previous 2 years are explicitly excluded from the trial. Participants with a household member who has a history of active pulmonary TB should have had a thorough evaluation for TB prior to study enrolment as recommended by a local infectious disease specialist or published local guidelines of TB control agencies.
- Presence of a transplanted organ (with the exception of a corneal transplant >3 months prior to screening).
- Malignancy within the past 5 years (except for squamous or basal cell carcinoma of the skin that has been treated with no evidence of recurrence).
- History of lymphoproliferative disease including lymphoma, or signs and symptoms suggestive of possible lymphoproliferative disease, such as lymphadenopathy of unusual size or location (such as nodes in the posterior triangle of the neck, infra-clavicular, epitrochlear, or periaortic areas), or splenomegaly.
- Known recent substance abuse (drug or alcohol).
- Poor tolerability of venepuncture required blood sampling during the study period.
- Planning to have surgery for RA or other significant surgery during the period of the study.
Trial locations and contacts
8 sites in 1 country.
8 sites in 1 country
United Kingdom8 sites
Cambridge University Hospitals NHS Foundation Trust, Addenbrooke's Hospital
Cambridge, CB2 0QQ
Barts Health NHS Trust, Experimental Medicine & Rheumatology, Mile End Hospital
London, E1 4DG
Barts Health NHS Trust,Department of Rheumatology,Whipps Cross University Hospital
London, E11 1NR
University College London Hospitals NHS Foundation Trust, Rheumatology Department
London, NW1 2PG
Imperial College Healthcare NHS Trust
London
Central Manchester University Hospitals NHS Foundation Trust, The Kellgren Centre for Rheumatology
Manchester, M13 9WL
The Newcastle upon Tyne Hospitals NHS Foundation Trust, Royal Victoria Infirmary
Newcastle, NE1 4LP
Oxford University Hospitals NHS Trust, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences
Oxford, OX3 7LD
About this study
Official title: A Study to Investigate the Role of IL-17 and Th17 Pathway Activation in RA Patients With Inadequate Response to Anti-TNFα Therapies
Preliminary data suggest that up-regulation of Interleukin -17 (IL-17) and the T-helper 17 (Th17) pathway occurs in rheumatoid arthritis (RA) patients on anti-Tumour Necrosis Factor (TNF) therapy who demonstrated an incomplete clinical response. A deeper understanding of this is required in order to determine whether IL-17 or the Th17 pathway is a valid target for intervention in this population to improve response outcome.
The study objective is to observe biologic naïve RA subjects on anti-TNF therapies and take measurements of peripheral blood and synovial tissue to assess differences in the IL-17 and Th17 pathways between responders and non-responders. The aim of the study is to test if increased Th17 pathway activity is present in subjects who do not respond clinically to anti-TNF therapy.
Clinical assessments, synovial bio-markers and ultrasound will be used as determinants of clinical response. The study may identify disease characteristics that determine which subjects may be more likely to respond to anti-TNF therapy, or those who may require either a different treatment option, or additional pathway inhibition in addition to TNF, in order to achieve clinical response.
Read the detailed description
The study aims to recruit 50 participants in total to this study. Potential candidate for this research include those that have active rheumatoid arthritis (RA) with the symptoms, and current medication status that qualify for anti-TNFα therapy. This is the treatment plan patients will be placed on regardless of whether or not they are taking part in the study; however, within the research environment, information will be gathered that may be able to help better understand the levels of response to anti-TNF treatment and why this differs between people. Participants will be asked to provide blood and urine samples as part of the research. Pieces of genetic material called ribonucleic acid (RNA) will be extracted from the study specific blood samples (and synovial tissue from patients that are part of the biopsy sub-study) provided by participants. This material will be analysed to reveal information about what genes are 'active' in the joint environment during anti-TNF treatment period. This information can tell us what proteins might be involved in the inflammation of affected joints and might also be able to predict what type of response patients will experience in response to different treatments. The analysis of research samples from this study will provide new information on the mechanisms for response/non-response to anti-TNF therapy.
Optional Biopsy sub-study A number of participants that have consented to the main study will be invited to take part in the optional biopsy sub-study. This will involve taking a biopsy of one of the affected joints via an ultrasound guided procedure. The procedure is minimally invasive and has good safety and tolerability with participants. The procedure is performed under local anaesthetic and removes tiny pieces of inflamed tissue (synovial tissue) from the lining of the joint using a needle under the guidance of an ultrasound scanner. This sub-study will collect tissue from affected joints to help answer the research questions in this study
Optional DNA genetic sampling Participants are also invited to take part in the optional DNA genetic sampling and are asked to contribute DNA samples for this study. The purpose of this optional part of the research study is to help understand how anti-TNF therapies work, and how they may cause side effects, to further understand rheumatoid arthritis, and to understand why some people respond to anti-TNF therapy while others do not. Genetic (genotyping) testing refers to patient sample being used for genetic research. This is the study of DNA and how it determines our traits. DNA research can also explain why some people respond well to their medications and others do not and can also provide reasons as to why some people develop some diseases and others do not. Samples from participants that have consented to the optional DNA genetic sampling will also be used for a type of genetic research called epigenetics. This is the study of chemical modifications of DNA that occur over time, without a change in DNA sequence. These modifications control the way cells produce proteins and respond to the environment. Epigenetics research is not a test to diagnose a person for a genetic disease or to determine whether a person may have a risk of developing a genetic disease. It is only used to understand prevailing disease and how drugs may work in different groups of people. In epigenetic testing, DNA samples from participants will be analysed to determine how this may influence response to anti-TNF therapy.
- Conditions
- Rheumatoid Arthritis
- Being tested
- Anti-TNF Biologics Therapy
- Medical subject headings
- Arthritis, Rheumatoid
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Anti-TNF Biologics TherapyDrug
Also called Etanercept (Enbrel), Adalimumab (Humira), Certolizumab Pegol(Cimzia)
What is being measured
The primary outcome is the main question the study is designed to answer.
Measure change in clinical response using Disease Activity Score DAS28 (C-Reactive Protein) at week 24 compared to baseline
Change in clinical response using Disease Activity Score DAS28 (C-Reactive Protein) at week 24 compared to baseline
Measured: Baseline and week 24
Secondary outcomes (1)
Change in Interleukin (IL)-17/T helper (Th)17 pathway activity in responders and non-responders to anti-Tumour Necrosis Factor (TNF) therapy
Correlation of the change in IL-17/Th17 pathway activity and ultrasound assessment of synovitis by grey-scale ultrasound and power Doppler
Measured: Baseline and week 24
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Dec 2015 (estimated)
- Study startMar 2015
- Primary completion24 May 2017
- Study completion24 May 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Rheumatoid ArthritisStudies of the same condition, open and under way.
- More trials run by Queen Mary University of LondonThe 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
- Cohort
- Time perspective
- Prospective
- Enrolment
- 60 participants (actual)
Sponsor and investigators
- Lead sponsor
- Queen Mary University of London
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Costantino Pitzalis, MD PhD FRCP, Study chair, Queen Mary University of London
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02620189
- Sponsor's protocol ID
- 009745
- Acronym
- THERAPIST
- Status last verified
- Nov 2015
- First submitted
- 12 Oct 2015
- Last updated
- 26 Sep 2022
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 26 Sep 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Study to Investigate the Role of IL-17 and Th17 Pathway Activation in RA Patients With Inadequate Response to Anti-TNFα Therapies
- ClinicalTrials.gov ID
- NCT02620189
- Acronym / sponsor ID
- THERAPIST / 009745
- Conditions
- Rheumatoid Arthritis
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 60 participants (actual)
- Lead sponsor
- Queen Mary University of LondonUniversity, hospital or other
- Study start
- Mar 2015
- Primary completion
- 24 May 2017 (actual)
- Study completion
- 24 May 2017 (actual)
- First posted
- 2 Dec 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.
Preliminary data suggest that up-regulation of Interleukin -17 (IL-17) and the T-helper 17 (Th17) pathway occurs in rheumatoid arthritis (RA) patients on anti-Tumour Necrosis Factor (TNF) therapy who demonstrated an incomplete clinical response. A deeper understanding of this is required in order to determine whether IL-17 or the Th17 pathway is a valid target for intervention in this population to improve response outcome.
The study objective is to observe biologic naïve RA subjects on anti-TNF therapies and take measurements of peripheral blood and synovial tissue to assess differences in the IL-17 and Th17 pathways between responders and non-responders. The aim of the study is to test if increased Th17 pathway activity is present in subjects who do not respond clinically to anti-TNF therapy.
Clinical assessments, synovial bio-markers and ultrasound will be used as determinants of clinical response. The study may identify disease characteristics that determine which subjects may be more likely to respond to anti-TNF therapy, or those who may require either a different treatment option, or additional pathway inhibition in addition to TNF, in order to achieve clinical response.
Detailed description
The study aims to recruit 50 participants in total to this study. Potential candidate for this research include those that have active rheumatoid arthritis (RA) with the symptoms, and current medication status that qualify for anti-TNFα therapy. This is the treatment plan patients will be placed on regardless of whether or not they are taking part in the study; however, within the research environment, information will be gathered that may be able to help better understand the levels of response to anti-TNF treatment and why this differs between people. Participants will be asked to provide blood and urine samples as part of the research. Pieces of genetic material called ribonucleic acid (RNA) will be extracted from the study specific blood samples (and synovial tissue from patients that are part of the biopsy sub-study) provided by participants. This material will be analysed to reveal information about what genes are 'active' in the joint environment during anti-TNF treatment period. This information can tell us what proteins might be involved in the inflammation of affected joints and might also be able to predict what type of response patients will experience in response to different treatments. The analysis of research samples from this study will provide new information on the mechanisms for response/non-response to anti-TNF therapy.
Optional Biopsy sub-study A number of participants that have consented to the main study will be invited to take part in the optional biopsy sub-study. This will involve taking a biopsy of one of the affected joints via an ultrasound guided procedure. The procedure is minimally invasive and has good safety and tolerability with participants. The procedure is performed under local anaesthetic and removes tiny pieces of inflamed tissue (synovial tissue) from the lining of the joint using a needle under the guidance of an ultrasound scanner. This sub-study will collect tissue from affected joints to help answer the research questions in this study
Optional DNA genetic sampling Participants are also invited to take part in the optional DNA genetic sampling and are asked to contribute DNA samples for this study. The purpose of this optional part of the research study is to help understand how anti-TNF therapies work, and how they may cause side effects, to further understand rheumatoid arthritis, and to understand why some people respond to anti-TNF therapy while others do not. Genetic (genotyping) testing refers to patient sample being used for genetic research. This is the study of DNA and how it determines our traits. DNA research can also explain why some people respond well to their medications and others do not and can also provide reasons as to why some people develop some diseases and others do not. Samples from participants that have consented to the optional DNA genetic sampling will also be used for a type of genetic research called epigenetics. This is the study of chemical modifications of DNA that occur over time, without a change in DNA sequence. These modifications control the way cells produce proteins and respond to the environment. Epigenetics research is not a test to diagnose a person for a genetic disease or to determine whether a person may have a risk of developing a genetic disease. It is only used to understand prevailing disease and how drugs may work in different groups of people. In epigenetic testing, DNA samples from participants will be analysed to determine how this may influence response to anti-TNF therapy.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
- Study population
- Subjects who fulfil the NICE guidelines for biologic anti-TNF therapy as their first line treatment following failure of standard disease modifying anti-rheumatic therapy will be recruited from various secondary care settings at a number of centres throughout the UK.
Key inclusion criteria (9 listed)
- Men and women ≥ 18 years of age
- An RA diagnosis as defined by the 2010 revised EULAR/ACR classification criteria.
- Subjects who fulfil the NICE guidelines for Biologic therapy as their first line treatment following failure of standard disease modifying anti-rheumatic therapy.
- Subjects may be on cDMARDs (or MTX monotherapy) one of which must be MTX. Participants should be receiving MTX for at least 2 months at a stable dose of 7.5-25 mg/week before Week 0 visit.
- Subjects may be on oral steroids (prednisone ≤10 mg/day, or equivalent corticosteroid) with a stable dose for the 4 weeks prior to Week 0 visit.
Key exclusion criteria (13 listed)
- Women who are pregnant or breast feeding.
- Previous use of Rheumatoid Arthritis anti-TNF biologics, or ANY other type of biologic therapy or Investigational Medicinal Product.
- Treatment with any other therapeutic agent targeted at reducing TNF within 3 months of screening.
- Serious infections (such as pneumonia or pyelonephritis) in the previous 3 months. Less serious infections (such as acute upper respiratory tract infection [colds] or simple urinary tract infection) need not be considered exclusions at the discretion of the investigator.
- Known HIV, Hepatitis B, or Hepatitis C infection.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Anti-TNF Biologics TherapyAlso: Etanercept (Enbrel), Adalimumab (Humira), Certolizumab Pegol(Cimzia) | Drug | – |
Primary outcome
Measure change in clinical response using Disease Activity Score DAS28 (C-Reactive Protein) at week 24 compared to baseline
Time frame: Baseline and week 24
Change in clinical response using Disease Activity Score DAS28 (C-Reactive Protein) at week 24 compared to baseline
1 secondary outcome
Change in Interleukin (IL)-17/T helper (Th)17 pathway activity in responders and non-responders to anti-Tumour Necrosis Factor (TNF) therapy
Time frame: Baseline and week 24
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Sep 2022.
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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.
Costantino Pitzalis, MD PhD FRCP study chair
Queen Mary University of London
8 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Rheumatoid Arthritis, run by Queen Mary University of London at 8 sites 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 9 inclusion and 13 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: finished, as of the sponsor's last update on 26 Sep 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 8 sites 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Measure change in clinical response using Disease Activity Score DAS28 (C-Reactive Protein) at week 24 compared to baseline (time frame: Baseline and week 24). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 26 Sep 2022.