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MyositisPhase 1NCT03912428

Novel PET Radioligand as an Inflammatory Biomarker in Musculoskeletal Conditions

A Phase 1 study testing 11C-MC1, Celecoxib and [11C]ER176 in people with Myositis and Inflammatory, run by National Institute of Mental Health (NIMH) at 1 site in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
Search all trials

Trial summary

Background: Inflammation plays a significant role in various disorders that involve neurodegeneration or autoimmune reaction as one of their mechanisms. PET scans can help detect inflammation. Two new drugs may create better PET images. Objective: To see if the drug [11C]MC1 can help image inflammation. Read more about this study

Who is it for?
Ages 18 to 99 years
Conditions the study is for
Myositis, Inflammatory, Rheumatoid Arthritis
What is being tested?
11C-MC1, Celecoxib and [11C]ER176
Could I receive a placebo?
No, everyone receives an active treatment
How many people
31 participants
Where
1 siteUnited States
Study dates
14 Jun 2019to 14 Jun 2024
Phase
Phase 1
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 99 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Healthy subjects
  • Aged 18 years or older.
  • Willing and able to complete all study procedures.
  • Able to provide informed consent.
  • Healthy based on medical history, physical examination, and laboratory testing.
  • Enrolled in protocol 01-M-0254 The Evaluation of Participants with Mood and Anxiety Disorders and Healthy Volunteers or 17-M-0181 Recruitment and Characterization of Healthy Research Volunteers for National Institute of Mental Health (NIMH) Intramural Studies.
Show all 24Show fewer
  • Be age and sex-matched with patient groups for the 15 subjects in the Phase 2.
  • RA patients
  • Aged 18 years or older.
  • Willing and able to complete all study procedures.
  • Able to provide informed consent.
  • Have been given a diagnosis of RA based on the published criteria (Aletaha et al., 2010).
  • Have moderate to severe symptoms, as defined by a Disease Activity Score in 28 joints with erythrocyte sedimentation rate (DAS28-ESR) score >3.2, but RA patients may be in remission for the repeat scan in phase 4.
  • IIM patients
  • Aged 18 years or older
  • Willing and able to complete all study procedures.
  • Able to provide informed consent.
  • Meets Bohan and Peter criteria ((Bohan and Peter, 1975a, b) for probable or definite dermatomyositis (DM) or polymyositis (PM), or
  • Meets criteria for inclusion body myositis (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.
  • Axial Spondyloarthritis (AxSpA) patients
  • Aged 18 years or older.
  • Willing and able to complete all study procedures.
  • Able to provide informed consent.
  • Have been given a diagnosis of AxSpA based on Assessment of Spondylo-Arthritis International Society (ASAS) criteria AxSpA.

Who cannot join

  • 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 that, in the opinion of the investigators, have the potential to affect the results or the safety of the participant.
  • These may 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
Show all 28Show fewer
  • History of uncontrolled gastroesophageal reflux disease (GERD), but not medically controlled GERD
  • Coagulation disorder
  • Thrombocytopenia
  • Glucose-6-phosphate dehydrogenase (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 poorly controlled hypertension
  • Current use of probenecid
  • Patients clinically in remission or who have low disease activity
  • Positive HIV infection
  • 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.).
  • Pregnancy or breastfeeding.
  • Participants must not have substance use disorder or alcohol use disorder. However, alcohol or cannabis use by themselves are not exclusion criteria, unless that use affects the function of daily life.
  • NIMH employees or an NIH employee who is a subordinate/relative/co-worker of the investigators.
  • These criteria will not be applied to the two healthy volunteers participating in the Phase 1 of this study*.
  • Healthy subjects
  • Clinically significant laboratory abnormalities based on tests performed under screening protocol 01-M-0254 or 17-M-0181.
  • AxSpA and 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).

Trial locations and contacts

1 site in 1 country.

United States1 site

  • National Institutes of Health Clinical Center

    Bethesda, Maryland, 20892

Other trials in United States

About this study

Official title: Evaluation of a Novel PET Radioligand as an Inflammatory Biomarker in Musculoskeletal Conditions

Background:

Inflammation plays a significant role in various disorders that involve neurodegeneration or autoimmune reaction as one of their mechanisms. PET scans can help detect inflammation. Two new drugs may create better PET images.

Read more

Objective:

  • To see if the drug [11C]MC1 can help image inflammation.

Eligibility:

  • People age 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.
Read the detailed description
  1. 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. Using wholebody imaging, 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. Using brain-dedicated imaging, this seeks to determine whether RA patients and healthy volunteers have specific binding in brain - i.e., uptake that can be blocked celecoxib.

II. Study population

Healthy volunteers (n = 17), patients with RA (n = 15), and patients with IIM (n = 15) will undergo whole-body PET/CT scans. Patients with AxSpA (n=15) will undergo two whole-body PET/MRI scans. In addition, healthy volunteers (n = 22) and patients with RA (n = 12) will have brain-dedicated imaging using [11C]MC1 concurrent with arterial blood sampling. Finally, 15 patients with RA will be imaged during a period of moderate to severe symptoms and after clinically indicated treatment for two to four months. Thus, the entire population will be healthy volunteers (n = 39), patients with RA (n = 42), patients with AxSpA (n=15) and patients with

IIM (n = 15).

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 genotype-matched 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. The [11C]ER176 scans are not mandatory and will be requested at the discretion of the PI.
  3. Phase 3: Twelve RA patients and 22 age- and sex-matched healthy subjects will undergo two brain-dedicated PET/CT scans, each using 20 mCi [11C]MC1, and concurrent with arterial blood sampling. The first scan will be a baseline scan, and the second will be after blockade by celecoxib.
  4. Phase 4: Fifteen RA patients will be imaged twice with [11C]MC: while having moderate to severe symptoms and after clinically-indicated therapy for about two to four months. Participants will have whole-body scan after injection of 15 mCi of [11C]MC1.

IV. Outcome measures

For whole body imaging, 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.

For brain-dedicated imaging, the density of COX-2 will be measured with pharmacokinetic modeling and expressed as distribution volume (VT).

Being tested
11C-MC1, Celecoxib, [11C]ER176, Positron Emission Tomography (PET)/computed tomography (CT) Scan
Keywords
Inflammatory, PET Imaging
Medical subject headings
Myositis, Arthritis, Rheumatoid

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • 11C-MC1Drug

    PET radioligand for Cyclooxygenase-2 (COX-2)

  • CelecoxibDrug

    Also called Celebrex

    Cyclooxygenase-2 (COX-2) inhibitor

  • [11C]ER176Drug

    Radioligand for 18-kDa Translocator Protein

  • Positron Emission Tomography (PET)/computed tomography (CT) ScanDiagnostic test

    Whole body or brain PET/CT scans

Study groups in NCT03912428
Study groupRoleWhat they receive
Phase 1: Pilot - Whole body scan in health participantsOtherHealthy participants receive about 10 mCi of [11C]MC1 intravenously followed by a whole body PET/CT scan. If radiation dose to selected body organs is within safety limit, Phase 2 of study was initiated
Receives: Drug: 11C-MC1; Diagnostic Test: Positron Emission Tomography (PET)/computed tomography (CT) Scan
Phase 2: Whole body PET/CT scans in patientsOtherParticipants with rheumatoid arthritis (RA), idiopathic inflammatory myopathies (IIM), or axial spondyloarthritis (AXSPA), had a baseline whole body PET/CT scan after about 15 mCi of [11C]MC1 followed by a second whole body PET/CT scan with about 15 mCi of [11C]MC1 intravenously after blockade with single dose of celecoxib 200-400 mg orally on same day.
Receives: Drug: 11C-MC1; Drug: Celecoxib; Diagnostic Test: Positron Emission Tomography (PET)/computed tomography (CT) Scan
Phase 2: Whole body PET/CT scans in healthy participantsOtherHealthy participants had a baseline whole body PET/CT scan after receiving about 15 mCi of [11C]MC1 followed by a second whole body PET/CT scan with about 15 mCi of [11C]MC1 intravenously after blockade with single dose of celecoxib 200-400 mg orally on same day. In a second visit, participants had a baseline whole body PET/CT scan after receiving about 15 mCi of [11C]ER176 followed by a second whole body PET/CT scan with about 15 mCi of [11C]ER176 intravenously after blockade with single dose of celecoxib 200-400 mg orally on same day.
Receives: Drug: 11C-MC1; Drug: Celecoxib; Drug: [11C]ER176; Diagnostic Test: Positron Emission Tomography (PET)/computed tomography (CT) Scan
Phase 3: Brain PET/CT scans in healthy participantsOtherHealthy participants had a baseline brain PET/CT scan after receiving about 20 mCi [11C]MC1 followed by a second brain PET/CT scan with 20 mCi [11C]MC1 intravenously after blockade with single dose of celecoxib 600 mg orally on same day. Participants had arterial blood sampling with each brain scan.
Receives: Drug: 11C-MC1; Drug: Celecoxib; Diagnostic Test: Positron Emission Tomography (PET)/computed tomography (CT) Scan

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Uptake of [11C]MC1 by Organs

    Participant received whole body PET/CT scan and radioligand uptake of [11C]MC1 in selected body regions of interest was quantified as a Standardized Uptake Value (SUV) using the Siemens Biograph Micro-Computed Tomography (mCT) with an injected dose of 9 mCi. Organ dosimetry was measured as dose per organ in Roentgen Equivalent Man (rem), which is absorbed dose times an organ-specific quality factor.

    Measured: Up to 120 minutes during each scan

  2. Uptake of [11C]MC1 by Organs - Gender Specific Organs

    Participant received whole body PET/CT scan and radioligand uptake of [11C]MC1 in selected body regions of interest was quantified as a Standardized Uptake Value (SUV) using the Siemens Biograph Micro-Computed Tomography (mCT) with an injected dose of 9 mCi. Organ dosimetry was measured as dose per organ in Roentgen Equivalent Man (rem), which is absorbed dose times an organ-specific quality factor.

    Measured: Up to 120 minutes during each scan

  3. Phase 2: [11C]MC1 Binding in Inflamed Body Parts - HANDS

    The uptake of [11C]MC1 before (baseline) and after blockade by single dose of celecoxib 400mg orally in inflamed regions of the body in patients. The radioligand uptake of [11C]MC1 during whole body PET/CT scans in selected regions of interest was quantified as a Standardized Uptake Value (SUV), which normalizes for injected activity and body weight, using Bruker's PMOD quantification software.

    Measured: Up to 120 minutes during each scan

  4. Phase 2: [11C]MC1 Binding in Non-inflamed Body Parts - HANDS

    The uptake of [11C]MC1 before (baseline) and after blockade by a single dose of celecoxib 400mg orally in non-inflamed regions of the body in healthy participants. The radioligand uptake of [11C]MC1 during whole body PET/CT scans in selected regions of interest was quantified as a Standardized Uptake Value (SUV), which normalizes for injected activity and body weight, using Bruker's PMOD quantification software.

    Measured: Up to 120 minutes during each scan

  5. Phase 2: [11C]MC1 Binding in Inflamed Body Parts - KNEES

    The uptake of [11C]MC1 before (baseline) and after blockade by a single dose of celecoxib 400mg orally in inflamed regions of the body in patients. The radioligand uptake of [11C]MC1 during whole body PET/CT scans in selected regions of interest was quantified as a Standardized Uptake Value (SUV), which normalizes for injected activity and body weight, using Bruker's PMOD quantification software.

    Measured: Up to 120 minutes during each scan

  6. Phase 2: [11C]MC1 Binding Between Non-inflamed Body - KNEES

    The uptake of [11C]MC1 before (baseline) and after blockade by a single dose of celecoxib 400mg orally in non-inflamed regions of the body in healthy participants. The radioligand uptake of [11C]MC1 during whole body PET/CT scans in selected regions of interest was quantified as a Standardized Uptake Value (SUV), which normalizes for injected activity and body weight, using Bruker's PMOD quantification software.

    Measured: Up to 120 minutes during each scan

  7. Whole Brain Volume of Distribution (VT)/ Free-fraction (fP) of [11C]MC1

    The volume of distribution (VT) of [11C]MC1 measured as the brain-to-plasma ratio using the 2-tissue compartmental modeling divided by free-fraction in the plasma of parent radioligand (fP) at baseline and two hours after blockade with single dose of 600 mg celecoxib orally.

    Measured: Up to 120 minutes during each scan

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted11 Apr 2019
  2. Study start14 Jun 2019
  3. Primary completion14 Jun 2024
  4. Study completion14 Jun 2024

Why it stopped: due to difficulty with participant recruitment and data futility

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Diagnosis
Allocation
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
31 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03912428
Sponsor's protocol ID
190079
Other IDs
19-M-0079
Status last verified
Aug 2025
First submitted
10 Apr 2019
Last updated
16 Sep 2025
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: This study will also comply with the NIH Data Sharing Policy and Policy on the Dissemination of NIH-Funded Clinical Trial Information and the Clinical Trials Registration and Results Information Submission rule.

Publications

  • Ikawa M, Lohith TG, Shrestha S, Telu S, Zoghbi SS, Castellano S, Taliani S, Da Settimo F, Fujita M, Pike VW, Innis RB; Biomarkers Consortium Radioligand Project Team. 11C-ER176, a Radioligand for 18-kDa Translocator Protein, Has Adequate Sensitivity to Robustly Image All Three Affinity Genotypes in Human Brain. J Nucl Med. 2017 Feb;58(2):320-325. doi: 10.2967/jnumed.116.178996. Epub 2016 Nov 17.

    PubMed 27856631

  • Kreisl WC, Jenko KJ, Hines CS, Lyoo CH, Corona W, Morse CL, Zoghbi SS, Hyde T, Kleinman JE, Pike VW, McMahon FJ, Innis RB; Biomarkers Consortium PET Radioligand Project Team. A genetic polymorphism for translocator protein 18 kDa affects both in vitro and in vivo radioligand binding in human brain to this putative biomarker of neuroinflammation. J Cereb Blood Flow Metab. 2013 Jan;33(1):53-8. doi: 10.1038/jcbfm.2012.131. Epub 2012 Sep 12.

    PubMed 22968319

  • van der Laken CJ, Elzinga EH, Kropholler MA, Molthoff CF, van der Heijden JW, Maruyama K, Boellaard R, Dijkmans BA, Lammertsma AA, Voskuyl AE. Noninvasive imaging of macrophages in rheumatoid synovitis using 11C-(R)-PK11195 and positron emission tomography. Arthritis Rheum. 2008 Nov;58(11):3350-5. doi: 10.1002/art.23955.

    PubMed 18975347

  • Aletaha D, Neogi T, Silman AJ, Funovits J, Felson DT, Bingham CO 3rd, Birnbaum NS, Burmester GR, Bykerk VP, Cohen MD, Combe B, Costenbader KH, Dougados M, Emery P, Ferraccioli G, Hazes JM, Hobbs K, Huizinga TW, Kavanaugh A, Kay J, Kvien TK, Laing T, Mease P, Menard HA, Moreland LW, Naden RL, Pincus T, Smolen JS, Stanislawska-Biernat E, Symmons D, Tak PP, Upchurch KS, Vencovsky J, Wolfe F, Hawker G. 2010 Rheumatoid arthritis classification criteria: an American College of Rheumatology/European League Against Rheumatism collaborative initiative. Arthritis Rheum. 2010 Sep;62(9):2569-81. doi: 10.1002/art.27584.

    PubMed 20872595

  • Bohan A, Peter JB. Polymyositis and dermatomyositis (first of two parts). N Engl J Med. 1975 Feb 13;292(7):344-7. doi: 10.1056/NEJM197502132920706. No abstract available.

    PubMed 1090839

  • Bohan A, Peter JB. Polymyositis and dermatomyositis (second of two parts). N Engl J Med. 1975 Feb 20;292(8):403-7. doi: 10.1056/NEJM197502202920807. No abstract available.

    PubMed 1089199

  • Shrestha S, Kim MJ, Eldridge M, Lehmann ML, Frankland M, Liow JS, Yu ZX, Cortes-Salva M, Telu S, Henter ID, Gallagher E, Lee JH, Fredericks JM, Poffenberger C, Tye G, Ruiz-Perdomo Y, Anaya FJ, Montero Santamaria JA, Gladding RL, Zoghbi SS, Fujita M, Katz JD, Pike VW, Innis RB. PET measurement of cyclooxygenase-2 using a novel radioligand: upregulation in primate neuroinflammation and first-in-human study. J Neuroinflammation. 2020 May 2;17(1):140. doi: 10.1186/s12974-020-01804-6.

    PubMed 32359360

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing 11C-MC1, Celecoxib and [11C]ER176 in people with Myositis and Inflammatory, run by National Institute of Mental Health (NIMH) at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 24 inclusion and 28 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 16 Sep 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 16 Sep 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Uptake of [11C]MC1 by Organs (time frame: Up to 120 minutes during each scan). The study lists 7 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03912428, which also lists 7 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Sep 2025.

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