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PET Imaging of Cyclooxygenase-2 in Multiple Sclerosis

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: NCT05062083
Recruitment Status : Recruiting
First Posted : September 30, 2021
Last Update Posted : July 1, 2022
Sponsor:
Collaborator:
University of Maryland
Information provided by (Responsible Party):
National Institutes of Health Clinical Center (CC) ( National Institute of Mental Health (NIMH) )

Brief Summary:

Background:

Multiple sclerosis (MS) is an autoimmune disease that has no cure. MRI is the main tool used in the study and treatment of people with MS. A tracer has been developed for cyclooxygenase-2 (COX-2), an enzyme found in the brain during inflammation. Researchers want to explore the role inflammation plays in MS and see if COX-2 is measurable in the brains of people with the disease.

Objective:

To see if COX-2 is detectable in the brains of individuals with MS.

Eligibility:

People ages 18 and older with MS who are otherwise healthy.

Design:

Participants will be screened with their medical history and a physical exam. They will have an EKG to check the electrical activity of the heart.

Participants study involvement requires 2 to 3 visits and will last between 1 week and 4 months.

Participants will have 2 PET scans of the brain. These might occur on the same day or on separate days. A small amount of a radioactive chemical will be injected through an intravenous catheter. A needle will be used to guide a thin plastic tube into an arm vein. The needle will be removed. Only the catheter will be left in the vein. The PET scanner is shaped like a doughnut. Participants will lie on a bed that slides in and out of the scanner. They will wear a plastic mask molded to fit the head. The scan will last about 90 minutes. Participants will receive the medication celecoxib orally about 2 hours before the second scan.

Participants will have blood tests.

Participants must avoid certain medications a month prior to the PET scans.

...


Condition or disease Intervention/treatment Phase
Multiple Sclerosis Drug: 11C-MCI Drug: 11C-PS13 Phase 2

Detailed Description:

Study Description: This study will examine whether cyclooxygenase 1 (COX-1) and cyclooxygenase 2 (COX-2) are elevated in the brain of individuals with Multiple Sclerosis (MS)

Objectives: To determine whether COX-1 and COX-2 are detectable in the brains of individuals with MS.

Endpoints:

Primary endpoint: Calculation of COX-1 and COX-2 densities from [11C]PS13 and [11C]MC1 PET scans, respectively, using baseline scans and scans after blockade with ketoprofen and celecoxib, respectively.

Secondary endpoint: 1) Comparison of [11C]PS13 and [11C]MC1 specific uptake in different types of MS lesions (active, chronic active, inactive) and in normal white matter. 2) Comparison of [11C]PS13 and [11C]MC1 specific uptake in the brain lesions of the same subjects

Study Population:

Sixteen (16) participants with MS will be recruited. Participants may be male or female, 18 years or older and enrolled in the HP-00079860 protocol at the University of Maryland in Baltimore (UMB).

Phase: 2

Description of Sites/Facilities Enrolling Participants:

This is a multisite protocol that will enroll patients from University of Maryland and screening and PET imaging will be performed at the NIH Clinical Center.

Description of Study Intervention:

Participants will be intravenously injected with up to 20 mCi of [11C]PS13 and [11C]MC1 twice, once at baseline and once after blockade by ketoprofen and celecoxib, respectively.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 16 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Diagnostic
Official Title: PET Imaging of Cyclooxygenases in Multiple Sclerosis
Actual Study Start Date : June 7, 2022
Estimated Primary Completion Date : April 11, 2025
Estimated Study Completion Date : April 11, 2025

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
One arm
All particpants will receive the same tests
Drug: 11C-MCI
Injected IV followed by PET scanning

Drug: 11C-PS13
Injected IV followed by PET Scanning




Primary Outcome Measures :
  1. Measure the concentration of radioligands [ Time Frame: 36 months ]
    SUVR between the lesion and a reference region such as the cerebellum.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years to 99 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria
  • INCLUSION CRITERIA:
  • Be male or female, aged >18.
  • Female participants of childbearing potential must be using a medically acceptable means of contraception.
  • Participants must be in good general health as evidenced by medical history and physical examination.
  • All participants must have been enrolled under UMB protocol HP-00079860 (In vivo assessment of meningeal inflammation and its clinical impact in multiple sclerosis by 7 Tesla MRI), P.I. Daniel Harrison and have agreed to contact for future research.

EXCLUSION CRITERIA:

  • Any medical contraindication to the procedures performed in the study, or any current severe medical or psychiatric illness other than MS. This includes contraindications to Celecoxib, such as aspirin sensitive asthma, and contraindications to ketoprofen, such as hypersensitivity to ketoprofen or history of upper or lower gastrointestinal bleeding.
  • Behavioral symptoms that would preclude the gathering of data for the study, or advanced disease such that subjects cannot provide assent.
  • Clinically significant abnormalities on EKG or safety labs. This includes CBC; acute care panel (Na, K, Cl, CO2, creatinine, glucose, urea nitrogen); hepatic panel (alkaline phosphatase, ALT, AST, bilirubin total, and bilirubin direct); mineral panel (albumin, calcium, magnesium, phosphorus).
  • MRI performed >90 days before or after the PET scan
  • Have taken NSAIDs for two weeks prior to the PET scan. Have taken aspirin, corticosteroids (except for topical creams), or immunosuppressants (except for FDAapproved disease-modifying therapy for MS) in the prior month.
  • Have other major neurological or medical diseases that may cause cognitive dysfunction, such as structural brain diseases, metabolic diseases, paraneoplastic syndromes, infectious diseases, or other significant neurological abnormalities.
  • Have an unstable medical condition that, in the opinion of the investigators, makes participation unsafe (e.g., an active infection or untreated malignancy).
  • Are unable to travel to the NIH.
  • Have 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.
  • Have an inability to lie flat and/or lie still on the camera bed for at least two hours, including claustrophobia, overweight greater than the maximum for the scanner, and uncontrollable behavioral symptoms, which will be screened by an interview with the patient and/or caregiver during the screening visit.
  • Pregnancy
  • HIV infection
  • Be NIMH staff or an NIH employee who is a subordinate/relative/co-worker of the investigators.

Exclusion of Children

Because this protocol has more than minimal risk from radiation exposure without possibility of direct benefit, inclusion of children is not appropriate.

Exclusion of Pregnant or Breastfeeding Women

Pregnant women will be excluded because this protocol involves exposure to ionizing radiation. Lactating women will be excluded because radioisotopes may be excreted in milk.

Exclusion of Participants who are HIV Positive

Persons with HIV infection are excluded because HIV infection itself may cause neuroinflammation, and we wish to specifically study the effect of MS on neuroinflammation.

Exclusion of Participation of NIH Staff or family members of study team members NIH staff and family members of study team members may not be enrolled in this study.


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): NCT05062083


Contacts
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Contact: Maria D Ferraris Araneta, C.R.N.P. (301) 496-9423 ferrarism@mail.nih.gov
Contact: Robert B Innis, M.D. (301) 594-1368 robert.innis@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)
University of Maryland
Investigators
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Principal Investigator: Robert B Innis, M.D. National Institute of Mental Health (NIMH)
Additional Information:
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Responsible Party: National Institute of Mental Health (NIMH)
ClinicalTrials.gov Identifier: NCT05062083    
Other Study ID Numbers: 10000483
000483-M
First Posted: September 30, 2021    Key Record Dates
Last Update Posted: July 1, 2022
Last Verified: May 19, 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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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) ):
PET Imaging
Multiple Sclerosis
Neuroinflammation
Neurological Symptoms
Cyclooxygenases
Additional relevant MeSH terms:
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Multiple Sclerosis
Sclerosis
Pathologic Processes
Demyelinating Autoimmune Diseases, CNS
Autoimmune Diseases of the Nervous System
Nervous System Diseases
Demyelinating Diseases
Autoimmune Diseases
Immune System Diseases
11C-PS13
Radiopharmaceuticals
Molecular Mechanisms of Pharmacological Action