Investigation of Immunological and Pharmacological Factors for Response to Adalimumab in Rheumatoid Arthritis (PROMETHEE)

January 5, 2023 updated by: Rennes University Hospital

Investigation of Immunological and Pharmacological Factors for Response to Adalimumab in Rheumatoid Arthritis, With Analysis of CD4 + Follicular Helper T Subpopulations

Interventional study with minimal risks and constraints, prospective, mono-centric.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

Rheumatoid arthritis (RA) is a chronic inflammatory disease with synovial tropism, characterized by joint pain and swelling, secondary to inflammation of the synovial membrane and which can lead to joint destruction, with the risk of a major functional disability. Biological treatments have revolutionized its management over the past 15 years. However, they are not effective in all patients, they are expensive, and are not without side effects sometimes severe.

Currently, there is no predictive factor for response to biotherapy beyond the severity criteria of rheumatoid arthritis (presence of erosions, presence of anti-Citrullinated Protein Antibody (ACPA), importance of biological and clinical inflammation ).

The role of T lymphocytes and B lymphocytes has been widely studied in rheumatoid arthritis. The activity of rheumatoid arthritis is associated with a Th1 and Th17 type CD4 + T polarization, with pro-inflammatory cytokine production and decreased Treg activity.

In recent years, a population of CD4 + T lymphocytes, Tfh (T follicular helper cells) has been demonstrated and seems likely to play an important role in the pathogenesis of rheumatoid arthritis. Physiologically these cells were initially described in the secondary lymphoid organs where they are essential for the survival and differentiation of B lymphocytes into antibody-secreting cells. More recently, they have been described in the blood (c Tfh for circulating T follicular helper cells) and appear to be a reflection of Tfh activity in tissues.

Several studies have focused on c Tfh in rheumatoid arthritis. A significantly higher level of c Tfh was observed in rheumatoid arthritis than in healthy controls. A significant positive correlation was also observed between the level of c Tfh and the titre of ACPA and between the rate of c Tfh and the activity of the rheumatoid arthritis, measured by the Disease Activity Score (DAS). However, each research group characterized the c Tfh t with different markers, which limits the comparison of the different results obtained.

The rate of c Tfh also appears to be influenced by treatments. In a Chinese rheumatoid arthritis study, the level of c Tfh was analyzed before and after one month of treatment with Methotrexate and phytotherapy with Tripterygium wilfordii. The rate of cTfh had significantly decreased in the responders whereas it had not decreased in the non responders. All of these first results, observed in a limited number of patients, are in favor of a relationship between the level of c Tfh and the activity and / or severity of rheumatoid arthritis, and on the other hand, suggest that variations in c Tfh might be related to response to treatment.

The analysis of peripheral blood lymphocyte cells has the advantage of ease of access, by simple venipuncture. However, these cells do not always accurately reflect the populations present within the synovial membrane. The analysis of the cells of the synovial membrane requires the realization of a biopsy, invasive gesture and incompatible with the practice in routine care. The analysis of the cells of the articular fluid would make it possible to better apprehend the resident populations of the synovial membrane without generating an over-risk for the patient. Indeed the gesture of joint puncture is justified in case of effusion by the diagnosis (to eliminate an infection) and therapeutic (to carry out if necessary an injection of corticosteroids). Rheumatoid arthritis joint fluids are inflammatory, defined by a number of nucleated elements greater than 2000 / mm3. The flow cytometry study, using the same phenotypic markers as those used for peripheral blood analysis, in patients in thrust will allow comparison of lymphocyte blood subpopulations and joint fluid.

The existence of a predictive serum biomarker of response or nonresponse to anti-TNFα therapy would improve the management of patients by avoiding delaying the use of potentially more effective treatment in patients Priori non-responders to an anti-TNF α biotherapy. If approximately 25% of the patients are not responding to a first biotherapy, it would be interesting to be able to identify them upstream, using a predictive marker, in order to orient them early to another therapy.

Remote infrared infrared spectroscopy, using a chalcogenide glass optical fiber, allows the study of the functional groups of the molecules present in a biological sample. It showed its ability, through the demonstration of changes in spectroscopic profiles, to discriminate samples representing physiological and pathological situations. This method has shown an interest in the early diagnosis of septic arthritis from joint puncture fluid, for the diagnosis of RA from serum and for staging of hepatic steatosis from serum.

The objective of this work is to investigate whether the quantitative and / or qualitative variations of different lymphocyte subpopulations (especially Tfh) in a rheumatoid arthritis population treated with the same anti-TNF alpha (Tumor Necrosis Factor ), Adalimumab, are likely to influence the response or non-response to treatment at 6 months.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
59

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • France
      • Rennes, France, 35033
        • Rennes University Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Rheumatoid arthritis diagnosed according to EULAR 2010 criteria (European League Against Rheumatism);
  • Active rheumatoid arthritis, defined by DAS 28> 3.2;
  • Corticotherapy systemic ≤ 15mg /day, stable for ≥ 15 days;
  • Refractory or intolerant rheumatoid arthritis with at least one chemical background treatment;
  • Previous biological treatment stopped for ≥ 3 months for monoclonal antibodies (except Rituximab) and 15 days for Etanercept;
  • Patients who have given written informed consent.
  • For healthy volunteers: subjects aged 18 coming to the French blood establishment of Rennes for a donation of blood

Exclusion Criteria:

  • Patient minor;
  • Presence of a contraindication to biological treatment;
  • Previous treatment with Rituximab;
  • Vaccination or surgery in the month preceding the study or planned within 3 months of inclusion;
  • Patient not affiliated to social security;
  • Major persons subject to legal protection (safeguard of justice, curatorship, guardianship), persons deprived of their liberty.
  • For healthy volunteers: Minor subject ; Subject not affiliated with social security ; Major persons subject to legal protection (legal safeguards, guardianship, tutorship), persons deprived of their liberty

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Other
  • Allocation: Non-Randomized
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Other: Rheumatoid arthritis - Adalimumab
Other: Adalimumab
It will be an interventional study with minimal risks and constraints, prospective, mono-centric, in current care. Patient management will not be changed during the study. It will be taken at two different tracking points (M0 and M3) 4 additional tubes and use of surplus articular fluid (M0 and M3).
Other Names:
  • Additional Biological Sample
Other: Healthy volunteer
Other: Healthy volunteers
Collection of 2 tubes of blood. The values of the quantitative study of lymphocyte subpopulations will be compared to those obtained from healthy blood donors to define the standards used in this study.
Other Names:
  • Recovery of blood tubes during a donation

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Patient responding or not responding to treatment with Adalimumab at 6 months defined by a value of Disease Activity Score 28 (DAS 28) ≤ 3.2.
Time Frame: 6 months
Disease Activity Score 28 (DAS 28) calculated in every patients after clinical examination.
6 months

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Patient responding or not responding to treatment with Adalimumab at 1 year defined by a value of Disease Activity Score 28 (DAS 28) ≤ 3.2.
Time Frame: 12 months
Disease Activity Score 28 (DAS 28) calculated in every patients after clinical examination.
12 months
Patient responding or not responding to treatment with Adalimumab at 6 months and 1 year defined by the SDAI scores
Time Frame: 6 and 12 months
SDAI score will be calculated in every patients after clinical examination.
6 and 12 months
Patient responding or not responding to treatment with Adalimumab at 6 months and 1 year defined by the CDAI scores
Time Frame: 6 and 12 months
CDAI score will be calculated in every patients after clinical examination.
6 and 12 months
Patient responding or not responding to treatment with Adalimumab at 6 months and 1 year defined by the HAQ scores
Time Frame: 6 and 12 months
HAQ will be calculated in every patients after self-assessment questionnaire.
6 and 12 months
Residual plasmatic Adalimumab concentration
Time Frame: 3, 6 and 12 months
3, 6 and 12 months
Count of Anti-Adalimumab antibody
Time Frame: 3, 6 and 12 months
3, 6 and 12 months
Second derivative spectrometric profiles
Time Frame: Baseline and 3 monts
Serum and joint fluid
Baseline and 3 monts

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Rennes University Hospital

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Aleth Perdriger, Rennes University Hospital

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
March 13, 2017

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
January 13, 2020

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
January 13, 2020

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
March 10, 2017

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
April 6, 2017

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
April 12, 2017

Study Record Updates

Last Update Posted (Estimate)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
January 6, 2023

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
January 5, 2023

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
January 1, 2023

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 35RC17_3063_PROMETHEE

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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