Novel PET Radioligands as Inflammatory Biomarkers in Rheumatoid Arthritis and Myositis

• Status: Recruiting
• Trial end date: 2024-02-22
• Target enrollment: 0
• Participant gender: All

Summary

Background:

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.

Objective:

To see if the drugs [11C]ER176 and [11C]MC1 can help image inflammation.

Eligibility:

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.

Design:

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:

Medical history

Physical exam

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 may 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.

• Phase: Phase 1/Phase 2
• Accepts Healthy Volunteers?: Accepts Healthy Volunteers

Details

• Lead Sponsor: National Institute of Mental Health (NIMH)
• Treatments: Celecoxib

Criteria

• INCLUSION CRITERIA:

1) Healthy subjects

• Age greater than or equal to 18.

• Willing and able to complete all study procedures.

• Able to give written informed consent.

• Medically healthy.

• Enrolled in 01-M-0254 The Evaluation of Participants with Mood and Anxiety Disorders and Healthy Volunteers (PI: Dr. Carlos Zarate) or 17-M-0181, Recruitment and Characterization of Healthy Research Volunteers for NIMH Intramural Studies (PI: Dr. Joyce Chung).

• Be age-, sex-, and genotype-matched with patient groups for the 15 subjects in the Phase 2.

• If female, no plans for pregnancy within the ensuing 3 months in the Phase 2.

2) RA patients

• Age greater than or equal to 18.

• Willing and able to complete all study procedures.

• Able to give written informed consent.

• Have been given a diagnosis of RA based on the published criteria

• Have moderate to severe symptoms, as defined by a DAS28-ESR score >3.2, but RA patients may be in remission for the repeat scan in phase 4.

• If female, no plans for pregnancy within the ensuing 3 months for studies using celecoxib and for five months for the longitudinal study (Phase 4).

3) IIM patients

• Age greater than or equal to 18.

• Willing and able to complete all study procedures.

• Able to give written informed consent.

• Meets Bohan and Peter criteria for probable or definite DM or PM, or

• Meets criteria for IBM as defined by Lloyd et al. : 1) finger flexor or quadriceps weakness, and 2) endomysial inflammation, and

3) either invasion of non-necrotic muscle fibers or rimmed vacuoles.

• If female, no plans for pregnancy within the ensuing 3 months.

EXCLUSION CRITIERIA:

1. Common for all participants

• Because non-steroidal anti-inflammatory drugs (NSAIDs) inhibit COX-2, subjects should not have taken NSAIDs or willow bark tea for two weeks prior to the PET scan.

• For Phase 2, 3 and 4 *contraindications to taking COX-2 inhibitors include:

• History of hypersensitivity reaction to COX inhibitors or History of aspirin- or NSAID-induced asthma;

• History of upper or lower gastrointestinal bleeding, gastritis, peptic ulcer disease;

• History of uncontrolled gastroesophageal reflux disease (GERD), but not medically-controlled GERD;

• Coagulation disorder;

• Thrombocytopenia;

• G6PD deficiency;

• History of gout;

• History of hepatic or renal impairment;

• History of cardiovascular disease or presence of cardiovascular risk factors such as uncontrolled or poorlycontrolled hypertension.

• Current use of probenecid

• Patients clinically in remission or who have low disease activity

• Positive HIV test.

• Any other history of severe medical illness or injury with the potential to affect study data interpretation or to be any medical contraindication to the procedures performed in the study, including active infection and untreated malignancy.

• Unable to travel to NIH

• Recent exposure to radiation related to research (e.g., PET from other research) that, when combined with this study, would be above the allowable limits.

• Inability to lie flat on camera bed for at least two hours, including claustrophobia and overweight greater than the maximum for the scanner (500 lb).

• Current pregnancy or breastfeeding.

• Current alcohol abuse or dependence.

• NIMH employees and staff or immediate family member of NIMH employee/staff.

• These criteria will not be applied to the two healthy volunteers participating in the Phase 1 of this study.

2. Healthy subjects

-Clinically significant laboratory abnormalities based on tests performed under screening protocol 01-M-0254 or 17-M-0181.

3. IIM patients

• Unable to have an MRI scan (e.g., pacemakers or other implanted electrical devices, brain stimulators, dental implants, aneurysm clips (metal clips on the wall of a large artery), metallic prostheses (including metal pins and rods, heart valves, and cochlear implants), permanent eyeliner, implanted delivery pumps, or shrapnel fragments, metal fragments in the eye).