This study has been transitioned to CTIS with ID 2024-513537-21-00 check the CTIS register for the current data. To investigate the association between quantitative changes in whole body F-18-PEG Folate PET/CT (Folate PET) after 4 weeks and clinical…
ID
Source
Brief title
Condition
- Autoimmune disorders
- Joint disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The association between quantitative changes in Folate PET after 4 weeks of
anti-TNF treatment and clinical response to therapy up to 26 weeks of
treatment in patients with established RA. Clinical follow-up up to 26 weeks
will be regarded as golden standard.
Secondary outcome
The association between quantitative Folate PET tracer uptake in joint(s) and
histological changes in synovial tissue over 4 weeks of anti-TNF treatment
(with particular focus on macrophage infiltration, FRβ expression and
macrophage polarization status).
Background summary
Rheumatoid arthritis (RA) is a chronic systemic connective tissue disease that
primarily affects the synovial joints. The inflammation is usually chronic, and
may cause progressive destruction of bone and cartilage, eventually leading to
loss of function. Recent international guidelines stress the importance of
starting effective treatment as early as possible. A new diagnostic tool for
early diagnostics and therapy monitoring could greatly reduce permanent
physical damage.
Positron emission tomography (PET) is a highly sensitive imaging technique that
enables monitoring of disease activity and therapeutic effects. PET tracers can
specifically target to cells or molecules of interest. The macrophage has been
shown to be a promising target for both early diagnostics and therapy
monitoring, because of its infiltration in synovium from the early development
of RA onwards. Studies by our research group have shown that macrophage PET
imaging can visualize inflammatory activity in rheumatoid arthritis, even at
subclinical level. The potential of PET to predict therapeutic outcome of RA
treatment has also been demonstrated, showing very early predictive power of
PET for outcome of anti-TNF and Rituximab treatment in RA.
Recently, our group developed a novel macrophage tracer: [18F]PEG Folate
(polyethylene glycol folate). [18F]PEG Folate binds to the β-isoform of the
folate receptor (FRβ), which was demonstrated to be expressed on macrophages in
synovial tissue of RA patients. [18F]PEG Folate showed an excellent arthritis
imaging profile in a translational approach (in vitro, in vivo work in an
animal model of arthritis and a clinical proof of concept study in RA
patients). Moreover, the tracer has been synthesized as an [18F]-tracer,
allowing for synthesis in a central GMP laboratory from where it can be shipped
to other hospitals.
Study objective
This study has been transitioned to CTIS with ID 2024-513537-21-00 check the CTIS register for the current data.
To investigate the association between quantitative changes in whole body
F-18-PEG Folate PET/CT (Folate PET) after 4 weeks and clinical response to
anti-TNF therapy at 26 weeks of treatment in patients with clinically active
established RA.
Study design
A multicentre, prospective cohort study in 20 clinically active, established RA
patients.
Study burden and risks
The total radiation burden will be about 12.4 mSv.
de Boelelaan 1117
Amsterdam 1081 HV
NL
de Boelelaan 1117
Amsterdam 1081 HV
NL
Listed location countries
Age
Inclusion criteria
• Patients must be at least 30 years of age
• Diagnosis of rheumatoid arthritis according to the 1987 revised criteria of
the American Rheumatism Association (ARA)13 and/or the 2010 ACR/EULAR
Rheumatoid Arthritis classification criteria.
• Patients with clinically active disease as assessed by a physician; with
arthritis in at least one synovial biopsy accessible joint and have a clinical
indication to start or restart (if stopped >12 weeks) with anti-TNF (either
Infliximab, Etanercept, Adalimumab or Certolizumab).
• Prior treatment with one anti-TNF agent (Adalimumab, Certolizumab,
Etanercept, Golimumab or Infliximab) is permitted, but may not be a primary
failure to any anti-TNF agent (defined as no response within the first 12 weeks
of treatment)
• Treatment with disease modifying anti-rheumatic drugs (DMARDS) and oral
corticosteroid up to 10 mg daily is allowed, provided that there is a stable
dose for at least 4 weeks prior to inclusion and during the study up to 12
weeks of follow up.
• Non-steroidal anti-inflammatory drugs (NSAID) is permitted, provided that
there is a stable dose for at least 4 weeks prior to inclusion and during the
study up to 12 weeks of follow up.
• Patients must be able to adhere to the study appointments and other protocol
requirements
• Patients must be capable of giving informed consent and the consent must have
been obtained prior to the study related procedures.
Exclusion criteria
• Use of intramuscular or intravenous corticosteroids within 4 weeks prior to
screening.
• Patients who received methotrexate and folic acid less than 7 days before
tracer injection.
• Treatment with any investigational drug within the previous 3 months
• Known pregnancy or breast feeding
• Research related radiation exposure (cumulative >=5 mSv) in the year before
inclusion
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EU-CTR | CTIS2024-513537-21-00 |
| EU-CTR | CTIS2024-513537-21-02 |
| EudraCT | EUCTR2018-004429-94-NL |
| CCMO | NL68286.029.19 |