Rheumatoid ArthritisNCT03736044
Reconstitution of CD4+CD25highCD127low/-Tcell
A study testing TNF-blockers suspension in patients with rheumatoid arthritis in people with Rheumatoid Arthritis, run by University Hospital of Ferrara.
Trial summary
Rheumatoid arthritis (RA) is a systemic disabling inflammatory disease, of autoimmune origin characterized by chronic synovial inflammation resulting in joint damage. Treg cell function in patients with active RA is assumed to be impaired, a trend that seems to be reversed by TNFalpha antagonist therapy. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Rheumatoid Arthritis
- What is being tested?
- TNF-blockers suspension in patients with rheumatoid arthritis
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 48 participants
- Where
- No sites listed yet
- Study dates
- 25 Nov 2013to 13 Mar 2017
- Phase
- Interventional
- 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
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- patients with RA fulfilling the 1987 ACR classification criteria (10) treated with anti-TNF and/or conventional DMARDs for at least 12 months, in prolonged remission (DAS28 <2.6 or DAS44 <1.6) for at least 6 months (checked in two consecutive visits 3 months apart), without Glucocorticosteroid (for at least 3 months, before), on a stable treatment for at least 3 months.
Who cannot join
- assumption of glucocorticosteroids within the three months before; confounding comorbidities such as fibromyalgia; chronic inflammatory disease other than RA; ongoing infections at the time of enrolment; recent trauma.
About this study
Official title: Analysis of T Cell Population to Obtain a Free-drug Remission in Patients Affected by Rheumatoid Athritis in Remission Phase Induced by TNF-blocker Therapy
Rheumatoid arthritis (RA) is a systemic disabling inflammatory disease, of autoimmune origin characterized by chronic synovial inflammation resulting in joint damage. Treg cell function in patients with active RA is assumed to be impaired, a trend that seems to be reversed by TNFalpha antagonist therapy. Remission is the current treatment goal in RA.
An increasing number of patients in clinical trials achieve this goal raising the question whether patients who have been in remission for a prolonged period (sustained remission) still need medication indefinitely. From a decade TNF-blocker therapy have represented a new treatment option for RA patients non responders to conventional DMARDs and some evidence are now available showing that sustainable remission can be maintained achieved after withdrawal of TNF blocker. Objectives: to verify whether in RA patients in prolonged clinical and instrumental remission the percentages of CD4+CD25highCD127low/- T cells could represent a reliable marker of immunological remission and, even more relevant, if the pharmacological reconstitution of this "immune-modulator" Tcell population could contribute to better identify patients with a low risk of relapse after cessation of TNF-blocker therapy. Methods: in RA patients, who fulfilled the 1987 ACR revised criteria, with disease duration ! 5 years, clinical [Disease Activity Score on 28 joints-DAS28 0.56 ×√(TJC28) + 0.28×√(SJC28) + 0.70×ln(ESR) + 0.014×GH.TJC= Tender Joints Count (from 0 to 28); SJC= Swollen Joints Count (from 0 to 28) ESR=Erythrocyte Sedimentation Rate GH= patient's assessment of general health (VAS range from 0 to 100 mm); disease's flare was considered if: DAS44 >=2.4/DAS28 >=3.2.)], instrumental (joint ultrasonography: sites to be explored wrists are II-III metacarpophalangeal joint bilaterally using Power Doppler signal (grading 0-3); any other joint will be studied if symptomatic) and immunological (circulating CD4+CD25highCD127low/-Tcells and inflammatory cytokines levels) examination will be performed in order to asses, at different levels, disease activity status. Expected results: to identify in RA patients treated with anti-TNF an "exit-strategy" from these drugs based on clinical, imaging and immunologic features indicative of a sustained remission and to verify whether such conditions are able to predict a low incidence of relapse.
Read the detailed description
- To evaluate the incidence of disease flare after cessation of anti-TNF therapy in patients that meet sustained clinical and instrumental remission criteria together with reconstitution of the CD4+CD25highCD127low/- Tcell population respect to those patients in the same remission status with persistent low CD4+CD25highCD127low/- Tcell population.
- Assessment of CD4+CD25highCD127low/- Tcell population behaviour induced by different drug treatments (anti-TNF vs DMARDs) in patient with RA who have achieved a prolonged remission status.
- To assess the predictive value of modifications of CD4+CD25highCD127low/- Tcell population in patients who relapse.
Study design: all RA patients satisfying inclusion criteria will undergo to a baseline clinical, instrumental and immunologic evaluation. Peripheral CD4+CD25highCD127low/- Tcell population will be checked for and patients will be stratified in 2 groups:
- Group A: patients on treatment with TNF-blockers plus DMARDs
- Group B: patients treated with DMARDs only (Methotrexate/Leflunomide), never treated with anti-TNF In addition a cohort of healthy subjects matched for sex and age will be used as a control.
Patient's blood samples will be centralized at the "Laboratories of Technology for Advanced Therapies" of the University of Ferrara (www.ltta.tecnopoloferrara.it) directed by Prof. Paola Secchiero.
In group A anti-TNF drugs will be withdrawn and patients will be followed up. Patients belonging to the group B will be followed up without any further intervention. A tight clinical monitoring will be instituted and disease flares-up will be recorded. In case of disease flare therapeutic adjustment will be provided to the patients by the attending specialist team accordingly to the current standard of care.
- Conditions
- Rheumatoid Arthritis
- Being tested
- TNF-blockers suspension in patients with rheumatoid arthritis
- Keywords
- Rheumatoid arthritis, Remission, T regulatory lymphocytes, Tumor Necrosis Factor-blocker 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.
TNF-blockers suspension in patients with rheumatoid arthritisDrug
in patients treated with anti-TNF the intervention consisted in anti-TNF drug withdrawal, after a preliminary careful examination of remission status; a 18 months (at least) follow up was performed.
| Study group | Role | What they receive |
|---|---|---|
| TNF-blockers withdrawal | Experimental | Patients on treatment with TNF-blockers plus DMARDs in which a withdrawal of anti-TNF therapy was made. Receives: Drug: TNF-blockers suspension in patients with rheumatoid arthritis |
| DMARDs control group | No intervention | Patients treated with DMARDs only (Methotrexate/Leflunomide), never treated with anti-TNF. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Proportion of subjects who flare-up after cessation of anti-TNF therapy after 24 months
disease flare-up defined as DAS 28 >3.2
Measured: 24 months
Secondary outcomes (6)
Proportion of subjects who are still in remission or il low disease activity after 3, 6, 9, 12, 15, 18, 21, 24 months
disease remission/low disease activity defined as DAS 28 <=3.2
Measured: 24 months
Swollen joint counts after 3, 6, 9, 12, 15, 18, 21, 24 months
Number of Swollen Joints (range from 0 to 28) at clinical examination
Measured: 24 months
Tender joint counts after 3, 6, 9, 12, 15, 18, 21, 24 months
Number of Tender joints (range from 0 to 28) at clinical examination
Measured: 24 months
Patient self assessment of pain (VAS) after 3, 6, 9, 12, 15, 18, 21, 24 months
Severity of pain measured by visual analogic scale (0-10)
Measured: 24 months
Physician's and patient's assessment of global disease activity (VAS) after 3, 6, 9, 12, 15, 18, 21, 24 months
Physician and Patient evaluation of Global disease activity measured by visual analogic scale (0-100)
Measured: 24 months
HAQ (Health Assessment Questionnaire) after 3, 6, 9, 12, 15, 18, 21, 24 months
Evaluation of disability by HAQ. There are 8 sections: dressing, arising, eating, walking, hygiene, reach, grip, and activities. There are 2 or 3 questions for each section. Scoring within each section is from 0 (without any difficulty) to 3 (unable to do).The 8 scores of the 8 sections are summed and divided by 8.
Measured: 24 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Nov 2018
- Study start25 Nov 2013
- Primary completion13 Mar 2017
- Study completion13 Mar 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.
- 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
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Other
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Model description
- * Group A: patients on treatment with TNF-blockers plus DMARDs * Group B: patients treated with DMARDs only (Methotrexate/Leflunomide), never treated with anti-TNF. In addition a cohort of healthy subjects matched for sex and age used as a control.
- Masking
- None (open label)
- Enrolment
- 48 participants (actual)
Sponsor and investigators
- Lead sponsor
- University Hospital of Ferrara
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Andrea Lo Monaco, University Hospital of Ferrara
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03736044
- Sponsor's protocol ID
- PRUa1GR-2013 -00000156
- Status last verified
- Nov 2018
- First submitted
- 11 Oct 2018
- Last updated
- 8 Nov 2018
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 8 Nov 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Analysis of T Cell Population to Obtain a Free-drug Remission in Patients Affected by Rheumatoid Athritis in Remission Phase Induced by TNF-blocker Therapy
- ClinicalTrials.gov ID
- NCT03736044
- Acronym / sponsor ID
- PRUa1GR-2013 -00000156
- Conditions
- Rheumatoid Arthritis
- Keywords
- Rheumatoid arthritis, Remission, T regulatory lymphocytes, Tumor Necrosis Factor-blocker therapy
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 48 participants (actual)
- Lead sponsor
- University Hospital of FerraraUniversity, hospital or other
- Study start
- 25 Nov 2013 (actual)
- Primary completion
- 13 Mar 2017 (actual)
- Study completion
- 13 Mar 2017 (actual)
- First posted
- 8 Nov 2018 (actual)
- 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.
Rheumatoid arthritis (RA) is a systemic disabling inflammatory disease, of autoimmune origin characterized by chronic synovial inflammation resulting in joint damage. Treg cell function in patients with active RA is assumed to be impaired, a trend that seems to be reversed by TNFalpha antagonist therapy. Remission is the current treatment goal in RA.
An increasing number of patients in clinical trials achieve this goal raising the question whether patients who have been in remission for a prolonged period (sustained remission) still need medication indefinitely. From a decade TNF-blocker therapy have represented a new treatment option for RA patients non responders to conventional DMARDs and some evidence are now available showing that sustainable remission can be maintained achieved after withdrawal of TNF blocker. Objectives: to verify whether in RA patients in prolonged clinical and instrumental remission the percentages of CD4+CD25highCD127low/- T cells could represent a reliable marker of immunological remission and, even more relevant, if the pharmacological reconstitution of this "immune-modulator" Tcell population could contribute to better identify patients with a low risk of relapse after cessation of TNF-blocker therapy. Methods: in RA patients, who fulfilled the 1987 ACR revised criteria, with disease duration ! 5 years, clinical [Disease Activity Score on 28 joints-DAS28 0.56 ×√(TJC28) + 0.28×√(SJC28) + 0.70×ln(ESR) + 0.014×GH.TJC= Tender Joints Count (from 0 to 28); SJC= Swollen Joints Count (from 0 to 28) ESR=Erythrocyte Sedimentation Rate GH= patient's assessment of general health (VAS range from 0 to 100 mm); disease's flare was considered if: DAS44 >=2.4/DAS28 >=3.2.)], instrumental (joint ultrasonography: sites to be explored wrists are II-III metacarpophalangeal joint bilaterally using Power Doppler signal (grading 0-3); any other joint will be studied if symptomatic) and immunological (circulating CD4+CD25highCD127low/-Tcells and inflammatory cytokines levels) examination will be performed in order to asses, at different levels, disease activity status. Expected results: to identify in RA patients treated with anti-TNF an "exit-strategy" from these drugs based on clinical, imaging and immunologic features indicative of a sustained remission and to verify whether such conditions are able to predict a low incidence of relapse.
Detailed description
- To evaluate the incidence of disease flare after cessation of anti-TNF therapy in patients that meet sustained clinical and instrumental remission criteria together with reconstitution of the CD4+CD25highCD127low/- Tcell population respect to those patients in the same remission status with persistent low CD4+CD25highCD127low/- Tcell population.
- Assessment of CD4+CD25highCD127low/- Tcell population behaviour induced by different drug treatments (anti-TNF vs DMARDs) in patient with RA who have achieved a prolonged remission status.
- To assess the predictive value of modifications of CD4+CD25highCD127low/- Tcell population in patients who relapse.
Study design: all RA patients satisfying inclusion criteria will undergo to a baseline clinical, instrumental and immunologic evaluation. Peripheral CD4+CD25highCD127low/- Tcell population will be checked for and patients will be stratified in 2 groups:
- Group A: patients on treatment with TNF-blockers plus DMARDs
- Group B: patients treated with DMARDs only (Methotrexate/Leflunomide), never treated with anti-TNF In addition a cohort of healthy subjects matched for sex and age will be used as a control.
Patient's blood samples will be centralized at the "Laboratories of Technology for Advanced Therapies" of the University of Ferrara (www.ltta.tecnopoloferrara.it) directed by Prof. Paola Secchiero.
In group A anti-TNF drugs will be withdrawn and patients will be followed up. Patients belonging to the group B will be followed up without any further intervention. A tight clinical monitoring will be instituted and disease flares-up will be recorded. In case of disease flare therapeutic adjustment will be provided to the patients by the attending specialist team accordingly to the current standard of care.
Study design
- Primary purpose
- Other
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- * Group A: patients on treatment with TNF-blockers plus DMARDs * Group B: patients treated with DMARDs only (Methotrexate/Leflunomide), never treated with anti-TNF. In addition a cohort of healthy subjects matched for sex and age used as a control.
| Arm | Type | Receives |
|---|---|---|
| TNF-blockers withdrawal | Experimental | Drug: TNF-blockers suspension in patients with rheumatoid arthritisPatients on treatment with TNF-blockers plus DMARDs in which a withdrawal of anti-TNF therapy was made. |
| DMARDs control group | No intervention | –Patients treated with DMARDs only (Methotrexate/Leflunomide), never treated with anti-TNF. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- patients with RA fulfilling the 1987 ACR classification criteria (10) treated with anti-TNF and/or conventional DMARDs for at least 12 months, in prolonged remission (DAS28 <2.6 or DAS44 <1.6) for at least 6 months (checked in two consecutive visits 3 months apart), without Glucocorticosteroid (for at least 3 months, before), on a stable treatment for at least 3 months.
Key exclusion criteria (1 listed)
- assumption of glucocorticosteroids within the three months before; confounding comorbidities such as fibromyalgia; chronic inflammatory disease other than RA; ongoing infections at the time of enrolment; recent trauma.
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 |
|---|---|---|
| TNF-blockers suspension in patients with rheumatoid arthritisin patients treated with anti-TNF the intervention consisted in anti-TNF drug withdrawal, after a preliminary careful examination of remission status; a 18 months (at least) follow up was performed. | Drug | TNF-blockers withdrawal |
Primary outcome
Proportion of subjects who flare-up after cessation of anti-TNF therapy after 24 months
Time frame: 24 months
disease flare-up defined as DAS 28 >3.2
6 secondary outcomes
Proportion of subjects who are still in remission or il low disease activity after 3, 6, 9, 12, 15, 18, 21, 24 months
Time frame: 24 months
Swollen joint counts after 3, 6, 9, 12, 15, 18, 21, 24 months
Time frame: 24 months
Tender joint counts after 3, 6, 9, 12, 15, 18, 21, 24 months
Time frame: 24 months
Patient self assessment of pain (VAS) after 3, 6, 9, 12, 15, 18, 21, 24 months
Time frame: 24 months
Physician's and patient's assessment of global disease activity (VAS) after 3, 6, 9, 12, 15, 18, 21, 24 months
Time frame: 24 months
HAQ (Health Assessment Questionnaire) after 3, 6, 9, 12, 15, 18, 21, 24 months
Time frame: 24 months
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 8 Nov 2018.
- 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.
The record lists no contact. Use the official record to reach the sponsor.
Questions about this trial
What is this clinical trial studying?
A study testing TNF-blockers suspension in patients with rheumatoid arthritis in people with Rheumatoid Arthritis, run by University Hospital of Ferrara.
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 1 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: finished, as of the sponsor's last update on 8 Nov 2018. Status can change between updates, so confirm with the study contact before making plans.
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?
Proportion of subjects who flare-up after cessation of anti-TNF therapy after 24 months (time frame: 24 months). 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 8 Nov 2018.