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Novel PET Radioligands as Inflammatory Biomarkers in Rheumatoid Arthritis and Myositis

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03912428
Recruitment Status : Recruiting
First Posted : April 11, 2019
Last Update Posted : January 9, 2020
Sponsor:
Information provided by (Responsible Party):
National Institutes of Health Clinical Center (CC) ( National Institute of Mental Health (NIMH) )

Brief 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 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

Detailed Description:

I. Objective

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.

III. Design

  1. 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).
  2. 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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 47 participants
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Diagnostic
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


Arm Intervention/treatment
Single arm
all groups get the same studies
Drug: Celecoxib
COX-2 inhibitor

Diagnostic Test: 11C-MC1
PET radioligand for COX-2

Diagnostic Test: 11C-ER176
PET radioligand for TSPO




Primary Outcome Measures :
  1. 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.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
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
  • If female, no plans for pregnancy within the ensuing 3 months.

    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, *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
    • 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 drug/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 and specified in Section 4.c Screening.

  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).

Information from the National Library of Medicine

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


Contacts
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Contact: Maria D Ferraris Araneta, C.R.N.P. (301) 496-9423 ferrarism@mail.nih.gov

Locations
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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    prpl@cc.nih.gov   
Sponsors and Collaborators
National Institute of Mental Health (NIMH)
Investigators
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Principal Investigator: Robert B Innis, M.D. National Institute of Mental Health (NIMH)

Additional Information:
Publications:
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Responsible Party: National Institute of Mental Health (NIMH)
ClinicalTrials.gov Identifier: NCT03912428    
Other Study ID Numbers: 190079
19-M-0079
First Posted: April 11, 2019    Key Record Dates
Last Update Posted: January 9, 2020
Last Verified: January 6, 2020

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by National Institutes of Health Clinical Center (CC) ( National Institute of Mental Health (NIMH) ):
Myositis
PET Imaging
Additional relevant MeSH terms:
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Myositis
Musculoskeletal Diseases
Muscular Diseases
Neuromuscular Diseases
Nervous System Diseases
Celecoxib
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anti-Inflammatory Agents
Antirheumatic Agents
Cyclooxygenase 2 Inhibitors
Cyclooxygenase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action