Rheumatoid ArthritisNCT01060098
T Cells and TNF (Tumor Necrosis Factor): The Impact of TNF Blockade
An observational study of Rheumatoid Arthritis and Ankylosing Spondylitis, run by Imperial College London at 1 site in United Kingdom.
Trial summary
We aim to translate these findings into patients with rheumatoid arthritis and other conditions treated with anti-TNF (anti-tumor necrosis factor) therapy, such as psoriatic arthritis and ankylosing spondylitis. Patients from rheumatology clinics within NHS (National Health Service) trusts will be recruited. Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Rheumatoid Arthritis, Ankylosing Spondylitis, Psoriatic Arthritis
- What is being tested?
- anti-TNF therapy (etanercept or adalimumab)
- How many people
- 48 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- Apr 2010to Dec 2012
- Phase
- Observational
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: Primary care clinic
Who may be able to join
- Only anti-TNF naïve patients will be included in this study
- Patients between 18 to 80 years of age
- Patients due to start treatment with anti-TNF blocking agents - etanercept or adalimumab
- Patients with rheumatoid arthritis
- Only patients meeting the 1987 American College of Rheumatology (ACR) revised classification criteria for rheumatoid arthritis will be included
- Patients should have active rheumatoid arthritis, defined by an initial DAS28 score >5.1
Show all 18Show fewer
- Patients should have at least 1 joint suitable for synovial biopsy
- Patients can be on concurrent DMARDs but they should have been on a stable dose of DMARD for at least 1 month prior to study entry
- Patients can be on a concurrent dose of glucocorticoids (up to 10mg daily) and they should have been on a stable dose for at least 4 weeks prior to study entry
- Patients with psoriatic arthritis
- Patients should have a secure diagnosis of psoriatic arthritis determined by a rheumatologist
- Patients with psoriatic arthritis included in this study should have evidence of concurrent psoriatic skin lesions at the time of study entry
- Patients should have at least one joint suitable for synovial biopsy
- Patients can be on concurrent DMARDs - they should be on a stable dose of DMARD for at least 1 month prior to study entry
- Patients with Ankylosing spondylitis
- Patient should fulfil the Modified New York Criteria for diagnosis of ankylosing spondylitis
- Patients can be on concurrent NSAIDs
- Patients can be on concurrent DMARDs - they should be on a stable dose of DMARD for at least 1 month prior to study entry
Who cannot join
- Patients who have been previously treated with anti-TNF therapy for whatever reason
- Patients with rheumatoid arthritis, psoriatic arthritis or ankylosing spondylitis who do not fulfil the diagnostic criteria for these conditions as above
- Patient who have received an intra-articular injection of steroids or have received an intra-muscular injection of depot steroid to treat disease flare in the preceding 4 weeks prior to commencing anti-TNF therapy.
- Patients with intercurrent, active infection of any type, excluding the common cold
Trial locations and contacts
1 site in 1 country.
United Kingdom1 site
Kennedy Institute Clinical Trials Unit, 4Wl, Charing Cross Hospital
London, W6 8RF
About this study
Official title: T Cells and TNF: The Impact of TNF Blockade on Effector T Cell Populations in Rheumatoid Arthritis and Other Conditions Treated With Anti-TNFalpha Agents
We aim to translate these findings into patients with rheumatoid arthritis and other conditions treated with anti-TNF (anti-tumor necrosis factor) therapy, such as psoriatic arthritis and ankylosing spondylitis. Patients from rheumatology clinics within NHS (National Health Service) trusts will be recruited. We will correlate disease activity assessed by clinical parameters, ultrasonography, and questionnaires with biomarkers in the blood and target tissues, such as synovium and skin.
Read the detailed description
Inflammatory arthritis particularly rheumatoid arthritis (RA), psoriatic arthritis and ankylosing spondylitis are potentially disabling conditions which cause joint pain, swelling and deformity and treatments are aimed at preventing these complications. Although treatment has improved with the advent of anti TNF alpha therapies, up to 30% of patients fail to respond to this treatment and in others, treatment is associated with significant side effects. The precise mechanisms of this remain unclear. In addition, there are no sensitive methods available to monitor or predict disease response to treatment aside from testing inflammatory markers in the blood. Understanding the mechanism of action and what governs response to anti TNF therapy will allow development of more specific therapies for inflammatory arthritis. Work in animal models of rheumatoid arthritis has characterised a novel cell type, Th17 cells, important in the inflammatory cascade which are affected in a particular way by anti TNF therapies and may underpin their mechanism of action and side effects.
- Being tested
- anti-TNF therapy (etanercept or adalimumab)
- Keywords
- Rheumatoid arthritis
- Medical subject headings
- Arthritis, Rheumatoid, Spondylitis, Ankylosing, Arthritis, Psoriatic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
anti-TNF therapy (etanercept or adalimumab)Drug
Also called Enbrel, Humira
Biological DMARD
| Study group | Role | What they receive |
|---|---|---|
| Rheumatoid arthritis | Participants with Rheumatoid arthritis Receives: Drug: anti-TNF therapy (etanercept or adalimumab) | |
| Ankylosing spondylitis | Participants with Ankylosing spondylitis Receives: Drug: anti-TNF therapy (etanercept or adalimumab) | |
| Psoriatic arthritis | Participants with Psoriatic arthritis Receives: Drug: anti-TNF therapy (etanercept or adalimumab) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Measurement of Effector T Helper Type 17 Cells in Peripheral Blood
The frequency of circulating Th17 cells was determined by IL17 enzyme-linked immunospot assay (Elispot) and flow cytometry (fluorescence-activated cell sorting (FACS)).
Measured: Week 0, Week 12
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Feb 2010 (estimated)
- Study startApr 2010
- Primary completionDec 2012
- Study completionDec 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Rheumatoid ArthritisStudies of the same condition, open and under way.
- More trials run by Imperial College 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
- Case-control
- Time perspective
- Prospective
- Enrolment
- 48 participants (actual)
Sponsor and investigators
- Lead sponsor
- Imperial College London
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Sonya Abraham, Principal investigator, Imperial College London
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01060098
- Sponsor's protocol ID
- 2104091
- Status last verified
- Jan 2020
- First submitted
- 29 Jan 2010
- Last updated
- 18 Jan 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Hull DN, Cooksley H, Chokshi S, Williams RO, Abraham S, Taylor PC. Increase in circulating Th17 cells during anti-TNF therapy is associated with ultrasonographic improvement of synovitis in rheumatoid arthritis. Arthritis Res Ther. 2016 Dec 23;18(1):303. doi: 10.1186/s13075-016-1197-5.
PubMed 28010726Hull DN, Williams RO, Pathan E, Alzabin S, Abraham S, Taylor PC. Anti-tumour necrosis factor treatment increases circulating T helper type 17 cells similarly in different types of inflammatory arthritis. Clin Exp Immunol. 2015 Sep;181(3):401-6. doi: 10.1111/cei.12626. Epub 2015 Jun 23.
PubMed 25766640
Study at a glance
From the registry record, last updated by the sponsor on 18 Jan 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- T Cells and TNF: The Impact of TNF Blockade on Effector T Cell Populations in Rheumatoid Arthritis and Other Conditions Treated With Anti-TNFalpha Agents
- ClinicalTrials.gov ID
- NCT01060098
- Acronym / sponsor ID
- 2104091
- Keywords
- Rheumatoid arthritis
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 48 participants (actual)
- Lead sponsor
- Imperial College LondonUniversity, hospital or other
- Study start
- Apr 2010 (actual)
- Primary completion
- Dec 2012 (actual)
- Study completion
- Dec 2012 (actual)
- First posted
- 2 Feb 2010 (estimated)
- Results
- Posted 2 Jan 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
We aim to translate these findings into patients with rheumatoid arthritis and other conditions treated with anti-TNF (anti-tumor necrosis factor) therapy, such as psoriatic arthritis and ankylosing spondylitis. Patients from rheumatology clinics within NHS (National Health Service) trusts will be recruited. We will correlate disease activity assessed by clinical parameters, ultrasonography, and questionnaires with biomarkers in the blood and target tissues, such as synovium and skin.
Detailed description
Inflammatory arthritis particularly rheumatoid arthritis (RA), psoriatic arthritis and ankylosing spondylitis are potentially disabling conditions which cause joint pain, swelling and deformity and treatments are aimed at preventing these complications. Although treatment has improved with the advent of anti TNF alpha therapies, up to 30% of patients fail to respond to this treatment and in others, treatment is associated with significant side effects. The precise mechanisms of this remain unclear. In addition, there are no sensitive methods available to monitor or predict disease response to treatment aside from testing inflammatory markers in the blood. Understanding the mechanism of action and what governs response to anti TNF therapy will allow development of more specific therapies for inflammatory arthritis. Work in animal models of rheumatoid arthritis has characterised a novel cell type, Th17 cells, important in the inflammatory cascade which are affected in a particular way by anti TNF therapies and may underpin their mechanism of action and side effects.
Study design
- Observational model
- Case-control
- Time perspective
- Prospective
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Rheumatoid arthritis | – | Drug: anti-TNF therapy (etanercept or adalimumab)Participants with Rheumatoid arthritis |
| Ankylosing spondylitis | – | Drug: anti-TNF therapy (etanercept or adalimumab)Participants with Ankylosing spondylitis |
| Psoriatic arthritis | – | Drug: anti-TNF therapy (etanercept or adalimumab)Participants with Psoriatic arthritis |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Primary care clinic
Key inclusion criteria (18 listed)
- Only anti-TNF naïve patients will be included in this study
- Patients between 18 to 80 years of age
- Patients due to start treatment with anti-TNF blocking agents - etanercept or adalimumab
- Patients with rheumatoid arthritis
- Only patients meeting the 1987 American College of Rheumatology (ACR) revised classification criteria for rheumatoid arthritis will be included
Key exclusion criteria (4 listed)
- Patients who have been previously treated with anti-TNF therapy for whatever reason
- Patients with rheumatoid arthritis, psoriatic arthritis or ankylosing spondylitis who do not fulfil the diagnostic criteria for these conditions as above
- Patient who have received an intra-articular injection of steroids or have received an intra-muscular injection of depot steroid to treat disease flare in the preceding 4 weeks prior to commencing anti-TNF therapy.
- Patients with intercurrent, active infection of any type, excluding the common cold
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 therapy (etanercept or adalimumab)Also: Enbrel, HumiraBiological DMARD | Drug | Ankylosing spondylitis, Psoriatic arthritis, Rheumatoid arthritis |
Primary outcome
Measurement of Effector T Helper Type 17 Cells in Peripheral Blood
Time frame: Week 0, Week 12
The frequency of circulating Th17 cells was determined by IL17 enzyme-linked immunospot assay (Elispot) and flow cytometry (fluorescence-activated cell sorting (FACS)).
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Jan 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 28010726Hull DN, Cooksley H, Chokshi S, Williams RO, Abraham S, Taylor PC. Increase in circulating Th17 cells during anti-TNF therapy is associated with ultrasonographic improvement of synovitis in rheumatoid arthritis. Arthritis Res Ther. 2016 Dec 23;18(1):303. doi: 10.1186/s13075-016-1197-5.
- Results publication: PubMed 25766640Hull DN, Williams RO, Pathan E, Alzabin S, Abraham S, Taylor PC. Anti-tumour necrosis factor treatment increases circulating T helper type 17 cells similarly in different types of inflammatory arthritis. Clin Exp Immunol. 2015 Sep;181(3):401-6. doi: 10.1111/cei.12626. Epub 2015 Jun 23.
- Individual participant dataSharing planned: No
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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.
Sonya Abraham principal investigator
Imperial College London
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 Rheumatoid Arthritis and Ankylosing Spondylitis, run by Imperial College London 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 18 inclusion and 4 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 18 Jan 2020. 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?
Yes. Results are posted in the registry (first posted 2 Jan 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Measurement of Effector T Helper Type 17 Cells in Peripheral Blood (time frame: Week 0, Week 12). 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 NCT01060098, which also lists 2 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 18 Jan 2020.