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PET Imaging of Cyclooxygenase in Multiple Sclerosis

Phase 2
Terminated
Conditions
Multiple Sclerosis
Interventions
Drug: 11C-MC1
Drug: 11C-PS13
Registration Number
NCT05062083
Lead Sponsor
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. Tracers have been developed for cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2), key enzymes that involved in neuroinflammation. Researchers want to explore the role inflammation plays in MS and see if COX-1 and COX-2 are measurable in the brains of people with the disease.

Objective:

To see if COX-1 and COX-2 are 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 3 to 5 visits and will last between 2 weeks and 4 months.

Participants will have two positron emission tomography (PET) scans of the brain for each tracer. Scans of the same tracer 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 for each tracer. Participants will receive the medication ketoprofen or 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.

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

Recruitment & Eligibility

Status
TERMINATED
Sex
All
Target Recruitment
7
Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
Participants with multiple sclerosis11C-MC1Participants had two brain positron emission tomography (PET) scan visits. In one visit, participants had a baseline \[11C\]PS13 scan followed by a second \[11C\]PS13 scan after blockade with ketoprofen 75 mg orally. In another visit, participants had baseline \[11C\]MC1 scan followed by a second scan with \[11C\]MC1 after blockade by a dose of celecoxib 600 mg orally. Participants receive injection of up to 20 millicurie (mCi) of \[11C\]PS13 or \[11C\]MC1 during each scan.
Participants with multiple sclerosis11C-PS13Participants had two brain positron emission tomography (PET) scan visits. In one visit, participants had a baseline \[11C\]PS13 scan followed by a second \[11C\]PS13 scan after blockade with ketoprofen 75 mg orally. In another visit, participants had baseline \[11C\]MC1 scan followed by a second scan with \[11C\]MC1 after blockade by a dose of celecoxib 600 mg orally. Participants receive injection of up to 20 millicurie (mCi) of \[11C\]PS13 or \[11C\]MC1 during each scan.
Participants with multiple sclerosisKetoprofenParticipants had two brain positron emission tomography (PET) scan visits. In one visit, participants had a baseline \[11C\]PS13 scan followed by a second \[11C\]PS13 scan after blockade with ketoprofen 75 mg orally. In another visit, participants had baseline \[11C\]MC1 scan followed by a second scan with \[11C\]MC1 after blockade by a dose of celecoxib 600 mg orally. Participants receive injection of up to 20 millicurie (mCi) of \[11C\]PS13 or \[11C\]MC1 during each scan.
Participants with multiple sclerosisCelecoxibParticipants had two brain positron emission tomography (PET) scan visits. In one visit, participants had a baseline \[11C\]PS13 scan followed by a second \[11C\]PS13 scan after blockade with ketoprofen 75 mg orally. In another visit, participants had baseline \[11C\]MC1 scan followed by a second scan with \[11C\]MC1 after blockade by a dose of celecoxib 600 mg orally. Participants receive injection of up to 20 millicurie (mCi) of \[11C\]PS13 or \[11C\]MC1 during each scan.
Primary Outcome Measures
NameTimeMethod
Standard Uptake Value Ratio (SUVR) of Lesions With Injection of [11C]PS1360-90 minutes after the start of PET scan

Standard uptake value (SUV) was measured by averaging the SUV of all lesion voxels or tissue contralateral to lesion voxels in the PET image with injection of \[11C\]PS13. The SUVR was calculated by averaging the SUV ratio between lesion or tissue contralateral to lesion voxels and the caudate from 60-90 minutes after the start of the PET scan.

Standard Uptake Value Ratio (SUVR) of Lesions With Injection of [11C]MC160-90 minutes after the start of PET scan

Standard uptake value (SUV) was measured by averaging the SUV of all lesion voxels or tissue contralateral to lesion voxels in the PET image with injection of \[11C\]MC1. The SUVR was calculated by averaging the SUV ratio between lesion or tissue contralateral to lesion voxels and the cerebellum from 60-90 minutes after the start of the PET scan.

Standard Uptake Value Ratio (SUVR) of Lesions With Injection of [11C]PS13 After Blockade With Ketoprofen60-90 minutes after the start of PET scan

Calculation of standard uptake value (SUV) by averaging the SUV of all lesion voxels or tissue contralateral to lesion voxels in the PET image with injection of \[11C\]PS13 after blockade with ketoprofen. Calculation of SUVR by averaging the SUV ratio between lesion or tissue contralateral to lesion voxels and the caudate from 60-90 minutes after the start of the PET scan.

Standard Uptake Value Ratio (SUVR) of Lesions With Injection of [11C]MC1 After Blockade With Celecoxib60-90 minutes after the start of PET scan

Calculation of standard uptake value (SUV) by averaging the SUV of all lesion voxels or tissue contralateral to lesion voxels in the PET image with injection of \[11C\]MC1 after blockade with celecoxib. Calculation of SUVR by averaging the SUV ratio between lesion or tissue contralateral to lesion voxels and the cerebellum from 60-90 minutes after the start of the PET scan.

Secondary Outcome Measures
NameTimeMethod
Standard Uptake Value Ratio (SUVR) of Chronic Active Lesions With Injection of [11C]MC160-90 minutes after the start of PET scan

Chronic active lesion is defined as the white matter lesion with paramagnetic outer rim in quantitative susceptibility maps (QSM). Standard uptake value (SUV) was measured by averaging the SUV of chronic active lesion voxels or contralateral normal appearing brain tissues in the \[11C\]MC1 PET image. The SUVR was calculated by averaging the SUV ratio between chronic active lesion or tissue contralateral to lesion voxels and the cerebellum from 60-90 minutes after the start of the PET scan.

Standard Uptake Value Ratio (SUVR) of Chronic Active Lesions With Injection of [11C]PS1360-90 minutes after the start of PET scan

Chronic active lesion is defined as the white matter lesion with paramagnetic outer rim in quantitative susceptibility maps (QSM). Standard uptake value (SUV) was measured by averaging the SUV of chronic active lesion voxels or contralateral normal appearing brain tissues in the \[11C\]PS13 PET image. The SUVR was calculated by averaging the SUV ratio between chronic active lesion or tissue contralateral to lesion voxels and the caudate from 60-90 minutes after the start of the PET scan.

Trial Locations

Locations (1)

National Institutes of Health Clinical Center

🇺🇸

Bethesda, Maryland, United States

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