Novel PET Radioligands as Inflammatory Biomarkers in Rheumatoid Arthritis and Myositis
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|ClinicalTrials.gov Identifier: NCT03912428|
Recruitment Status : Recruiting
First Posted : April 11, 2019
Last Update Posted : January 9, 2020
Inflammation can play a role in diseases like heart disease and rheumatoid arthritis. PET scans can help detect inflammation. Two new drugs may create better PET images.
To see if the drugs [11C]ER176 and [11C]MC1 can help image inflammation.
People ages 18 and older with rheumatoid arthritis or idiopathic inflammatory myopathy (IIM).
Healthy volunteers enrolled in protocol 01-M-0254 or 17-M-0181 are also needed.
Healthy participants will be screened under protocol 01-M-0254 or 17-M-0181.
Participants with arthritis or IIM will have a screening visit. This will include:
Blood and urine tests
Possible CT or X-ray: A machine will take pictures of the body.
Healthy participants will have 1 or 2 visits. They may have urine tests. They may take the drug celecoxib by mouth. They will have a PET scan. A small amount of one or both study drugs will be injected through a catheter: A needle will guide a thin plastic tube into an arm vein. Another catheter will draw blood. They will like on a bed that slides into a machine. Their vital signs and heart activity will be measured.
Participants with arthritis will have up to 2 visits after screening. They will take celecoxib and have PET scans.
Participants with IIM will have up to 3 visits after screening. At 1 or 2 visits, they will take celecoxib and have PET scans. They will have 1 visit where they have an MRI: They will lie on a table that slides into a machine. The machine takes pictures of the body.
Sponsoring Institution: National Institute of Mental Health
|Condition or disease||Intervention/treatment||Phase|
|Myositis||Drug: Celecoxib Diagnostic Test: 11C-MC1 Diagnostic Test: 11C-ER176||Phase 1|
18-kDa translocator protein (TSPO) and cyclooxygenase-2 (COX-2) are both implicated in the pathophysiology of various inflammatory disorders, suggesting that both may serve as potential biomarkers of inflammation in brain as well as periphery. Our laboratory recently developed two new radioligands: [11C]ER176 to image TSPO and [11C]MC1 to image COX-2. This study seeks to determine whether PET imaging using these new radioligands can differentiate two inflammatory conditions rheumatoid arthritis (RA) and idiopathic inflammatory myopathies (IIM) from healthy conditions. To determine if [11C]MC1 uptake is specific to COX-2, we will also conduct a blocking study with a selective COX-2 inhibitor (celecoxib) in both [11C]MC1 and [11C]ER176 scans; celecoxib is expected to block uptake of [11C]MC1 but not [11C]ER176.
II. Study population
Healthy volunteers (n = 17), patients with RA (n = 15), and patients with IIM (n = 15) will undergo whole-body PET/CT.
- Phase 1: We will begin by injecting up to 10 mCi of [11C]MC1 in one healthy male and one healthy female and then conducting a whole body PET scan. Uptake will be measured in the ovaries and testes, and the dose of radioactivity will be calculated. We will proceed only if the dose to these organs with the higher injected activity proposed for Phase 2 will not exceed the limits specified by the Radioactive Drug Research Committee (RDRC).
- Phase 2: Fifteen RA patients, 15 IIM patients, and 15 age-, sex-, and genotypematched healthy subjects will undergo two whole-body PET/CT scans using 15 mCi of [11C]ER176 on one day and two whole-body PET/CT scans using 15 mCi of [11C]MC1 on another day. The first scan on each day will serve as the baseline scan for comparison; the second scan on each day will be a blocking study using celecoxib.
IV. Outcome measures
Radioligand uptake in a selected region of interest will be quantified as a Standardized Uptake Value (SUV), which normalizes for injected activity and body weight. Possible differences in actual blood radioligand level will be adjusted by venous blood data obtained during the PET scan. Regional uptake after blockade with celecoxib will be expressed as a percentage of the baseline value. The baseline uptake and the percentage blockade by celecoxib of each radioligand will be compared between patients and healthy subjects as well as between inflamed and non-inflamed regions of the body in RA and IIM patients.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||47 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||None (Open Label)|
|Official Title:||Evaluation of Novel PET Radioligands as Inflammatory Biomarkers in Rheumatoid Arthritis and Myositis|
|Actual Study Start Date :||June 14, 2019|
|Estimated Primary Completion Date :||February 2, 2022|
|Estimated Study Completion Date :||February 2, 2022|
all groups get the same studies
Diagnostic Test: 11C-MC1
PET radioligand for COX-2
Diagnostic Test: 11C-ER176
PET radioligand for TSPO
- Uptake of the radioligands in the affected body area [ Time Frame: 2 hours ]Radioligand uptake in a selected region of interest will be quantified as a Standardized Uptake Value (SUV), which normalizes for injected activity and body weight. Possible differences in actual blood radioligand level will be adjusted by venous blood data obtained during the PET scan. Regional uptake after blockade with celecoxib will be expressed as a percentage of the baseline value. The baseline uptake and the percentage blockade by celecoxib of each radioligand will be compared between patients and healthy subjects as well as between inflamed and non-inflamed regions of the body in RA and IIM patients.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03912428
|Contact: Maria D Ferraris Araneta, C.R.N.P.||(301) firstname.lastname@example.org|
|United States, Maryland|
|National Institutes of Health Clinical Center||Recruiting|
|Bethesda, Maryland, United States, 20892|
|Contact: For more information at the NIH Clinical Center contact Office of Patient Recruitment (OPR) 800-411-1222 ext TTY8664111010 email@example.com|
|Principal Investigator:||Robert B Innis, M.D.||National Institute of Mental Health (NIMH)|