PET Imaging of Cyclooxygenase in Multiple Sclerosis

NCT05062083 | Terminated Phase 2 Results FDA Drug

• 2 other identifiers: 10000483000483-M
• Study Type: interventional
• Target: 7
• Locations: 1 country
• Sites: 1

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.

Conditions

Multiple Sclerosis

Keywords

PET Imaging; Multiple Sclerosis; Neuroinflammation; Neurological Symptoms; Cyclooxygenases

Outcome Measures

Primary Outcomes (4)

• Standard Uptake Value Ratio (SUVR) of Lesions With Injection of [11C]PS13

  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.

  60-90 minutes after the start of PET scan

• Standard Uptake Value Ratio (SUVR) of Lesions With Injection of [11C]MC1

  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.

  60-90 minutes after the start of PET scan

• Standard Uptake Value Ratio (SUVR) of Lesions With Injection of [11C]PS13 After Blockade With Ketoprofen

  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.

  60-90 minutes after the start of PET scan

• Standard Uptake Value Ratio (SUVR) of Lesions With Injection of [11C]MC1 After Blockade With Celecoxib

  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.

  60-90 minutes after the start of PET scan

Secondary Outcomes (2)

• Standard Uptake Value Ratio (SUVR) of Chronic Active Lesions With Injection of [11C]PS13

  60-90 minutes after the start of PET scan

• Standard Uptake Value Ratio (SUVR) of Chronic Active Lesions With Injection of [11C]MC1

  60-90 minutes after the start of PET scan

Study Arms (1)

Participants with multiple sclerosis

EXPERIMENTAL

Participants 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.

Drug: 11C-MC1; Drug: 11C-PS13; Drug: Ketoprofen; Drug: Celecoxib

Interventions

11C-MC1 DRUG

Up to 20 mCi injected IV followed by PET scanning

Participants with multiple sclerosis

11C-PS13 DRUG

Up to 20 mCi injected IV followed by PET Scanning

Participants with multiple sclerosis

Ketoprofen DRUG

Ketoprofen 75 mg orally once

Participants with multiple sclerosis

Celecoxib DRUG

celecoxib 600 mg orally once

Participants with multiple sclerosis

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Aged 18 years and older.
• Female participants of childbearing potential must be using a medically acceptable means of contraception.
• Able to provide informed consent.
• In good general health as evidenced by medical history and physical examination.
• Enrolled under University of Maryland in Baltimore (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.

You may not qualify if:

• 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 complete blood count (CBC); acute care panel (Na, K, Cl, CO2, creatinine, glucose, urea nitrogen); hepatic panel \[alkaline phosphatase, alanine aminotransferase (ALT), aspartate aminotransferase (AST), bilirubin total, and bilirubin direct\]; mineral panel (albumin, calcium, magnesium, phosphorus).
• MRI performed \>180 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 FDA approved 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 National Institute of Mental Health (NIMH) staff or an NIH employee who is a subordinate/relative/co-worker of the investigators.
• 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.
• 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.

Sponsors & Collaborators

• National Institute of Mental Health (NIMH): lead
• University of Maryland: collaborator

Study Sites (1)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

Location

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Multiple Sclerosis; Neuroinflammatory Diseases; Neurologic Manifestations

Interventions

(11C)-MC1; 11C-PS13; Ketoprofen; Celecoxib

Condition Hierarchy (Ancestors)

Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Demyelinating Diseases; Autoimmune Diseases; Immune System Diseases; Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Signs and Symptoms

Intervention Hierarchy (Ancestors)

Phenylpropionates; Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals; Benzenesulfonamides; Sulfonamides; Amides; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Sulfones; Sulfur Compounds; Pyrazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Dr. Robert Innis
• Organization: National Institute of Mental Health (NIMH)

robert.innis@nih.gov

301-594-1368

Study Officials

• Robert B Innis, M.D.

  National Institute of Mental Health (NIMH)

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 29, 2021
• First Posted: September 30, 2021
• Study Start: June 7, 2022
• Primary Completion: September 5, 2023
• Study Completion: January 30, 2024
• Last Updated: June 27, 2024
• Results First Posted: June 27, 2024

Record last verified: 2024-01

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL
• Time Frame: 18 months after closure of protocol
• Access Criteria: Biomedical Translational Research Information System (BTRIS)

Locations

US (1)