Primary aim: Stepwise feasibility study to investigate whether intravenously administered macrophage tracers [11C]DPA-713, [18F]DPA-714 and/or [18F]PEG-folate accumulate in inflamed joints of rheumatoid arthritis patients using PET(-CT).Secondary…
ID
Source
Brief title
Condition
- Autoimmune disorders
- Joint disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Standardized uptake values (SUV) in arthritic joints
Target-to-background ratio (i.e uptake in arthritic joints divided by uptake in
peri-articular tissue).
Secondary outcome
Not applicable
Background summary
Rheumatoid Arthritis (RA) is a disabling disease, in particular when it is not
treated early and effectively. During the last decade, treatment of RA has
changed dramatically. It appears that early and aggressive treatment with
intensive monitoring results in a slow down or complete standstill of further
joint damage and in improvement of disability. Early initiation of treatment
requires early detection of arthritis.
It is known that subclinical joint inflammation may precede clinical signs like
joint pain and swelling and can induce joint damage. Discovery of subclinical
arthritis may offer a window of opportunity to advance initiation of therapy in
order to prevent joint damage and further improve clinical outcome. Therefore,
there is a need for biomarkers that can predict the therapeutic outcome to
allow for a timely switch to effective therapy in case of treatment failure.
Visualisation of macrophages may be a potential biomarker to detect early RA
and to monitor therapeutic effects.
Recently, we demonstrated visualisation of macrophages in preclinical arthritis
of RA patients by positron emission tomography with the radiolabeled macrophage
receptor ligand [11C]-(R)-PK11195.
However, identification of PET positive joints was often difficult due to the
relatively high level of background binding of [11C]-(R)-PK11195 in surrounding
tissues, limiting the use of this tracer for diagnostics of early disease.
Therefore more specific candidate macrophage tracers [11C]DPA-713, [18F]DPA-714
and [18F]PEG-Folate will be tested in this study protocol.
In vitro competition binding studies with DPA-713, DPA-714 and F-PEG-folate
demonstrate high affinity to their receptors.
Ex vivo PET imaging studies show that all tracers accumulate in arthritic
joints of rats with antigen-induced arthritis in the knee.
.
Study objective
Primary aim: Stepwise feasibility study to investigate whether intravenously
administered macrophage tracers [11C]DPA-713, [18F]DPA-714 and/or
[18F]PEG-folate accumulate in inflamed joints of rheumatoid arthritis patients
using PET(-CT).
Secondary aim: Comparison of imaging potential of new macrophage tracers
[11C]DPA-713, [18F]DPA-714 and [18F]PEG-folate to the previously tested
macrophage tracer [11C]-(R)-PK11195.
Study design
Comparison of the macrophage PET tracers will be performed in a stepwise
manner.
In phase 1, [18F]DPA-714 will be compared to [11C]-(R)-PK11195.
In phase 2, the tracer from phase 1 with the best imaging characteristics will
be compared to [11C]DPA-713.
In phase 3, the best new macrophage tracer with the best imaging
characteristics from phase 2 will be compared to [18F]PEG-Folate.
In each phase a minimum of three and a maximum of six patients will be
included. Individual patients will participate in only one phase of the
study.
Study burden and risks
Burden and risks
- Collection of blood; can cause local bruises
- Drip (2x); can cause local bruises
- 2x PET-CT scan; radiation burden of in total < 10 mSv
- Very small chance of allergic reaction to PET tracer
De Boelelaan 1117
Amsterdam 1081 HV
NL
De Boelelaan 1117
Amsterdam 1081 HV
NL
Listed location countries
Age
Inclusion criteria
1. Men or women, * 18 years old
2. Diagnosis of rheumatoid arthritis according to the 1987 revised criteria of the American Rheumatism Association (ARA) and/or the 2010 ACR/EULAR Rheumatoid Arthritis Classification Criteria.
3. Patients with obvious clinical arthritis activity assessed by a physician, in at least 2 hand, wrist or knee joints.
4. Treatment with disease modifying anti-rheumatic drugs (DMARDS) and oral corticosteroids up to 10 mg daily is allowed. Non-steroidal anti-inflammatory drugs (NSAID) is permitted, provided that there is a stable dose for at least 1 month. Furthermore, prior or current treatment with biologics is permitted, provided that there is a stable dosing schedule for at least 3 months.
5. Patients must be able to adhere to the study appointments and other protocol
requirements.
6. Patients must be capable of giving informed consent and the consent must have been
obtained prior to the study related procedures.
Exclusion criteria
1. Use of intramuscular or intravenous corticosteroids within 4 weeks prior to screening.
2. Treatment with any investigational drug within the previous 3 months.
3. Pregnancy or breast-feeding.
4. Previous exposure to radioactivity with a yearly cumulative dose of * 5 mSv.
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 |
|---|---|
| EudraCT | EUCTR2013-001755-12-NL |
| CCMO | NL41366.029.13 |