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PET Imaging of Cyclooxygenase-2 in Multiple Sclerosis

Primary Purpose

Multiple Sclerosis

Status
Recruiting
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
11C-MCI
11C-PS13
Sponsored by
National Institute of Mental Health (NIMH)
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional diagnostic trial for Multiple Sclerosis focused on measuring PET Imaging, Multiple Sclerosis, Neuroinflammation, Neurological Symptoms, Cyclooxygenases

Eligibility Criteria

18 Years - 99 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers
  • 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.

Sites / Locations

  • National Institutes of Health Clinical CenterRecruiting

Arms of the Study

Arm 1

Arm Type

Other

Arm Label

One arm

Arm Description

All particpants will receive the same tests

Outcomes

Primary Outcome Measures

Measure the concentration of radioligands
SUVR between the lesion and a reference region such as the cerebellum.

Secondary Outcome Measures

Full Information

First Posted
September 29, 2021
Last Updated
August 17, 2023
Sponsor
National Institute of Mental Health (NIMH)
Collaborators
University of Maryland
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1. Study Identification

Unique Protocol Identification Number
NCT05062083
Brief Title
PET Imaging of Cyclooxygenase-2 in Multiple Sclerosis
Official Title
PET Imaging of Cyclooxygenases in Multiple Sclerosis
Study Type
Interventional

2. Study Status

Record Verification Date
August 14, 2023
Overall Recruitment Status
Recruiting
Study Start Date
June 7, 2022 (Actual)
Primary Completion Date
April 11, 2025 (Anticipated)
Study Completion Date
April 11, 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
National Institute of Mental Health (NIMH)
Collaborators
University of Maryland

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No

5. Study Description

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. ...
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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Multiple Sclerosis
Keywords
PET Imaging, Multiple Sclerosis, Neuroinflammation, Neurological Symptoms, Cyclooxygenases

7. Study Design

Primary Purpose
Diagnostic
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
16 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
One arm
Arm Type
Other
Arm Description
All particpants will receive the same tests
Intervention Type
Drug
Intervention Name(s)
11C-MCI
Intervention Description
Injected IV followed by PET scanning
Intervention Type
Drug
Intervention Name(s)
11C-PS13
Intervention Description
Injected IV followed by PET Scanning
Primary Outcome Measure Information:
Title
Measure the concentration of radioligands
Description
SUVR between the lesion and a reference region such as the cerebellum.
Time Frame
36 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
99 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
INCLUSION CRITERIA: 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 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 >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 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. INCLUSION OF VULNERABLE PARTICIPANT None
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Maria D Ferraris Araneta, C.R.N.P.
Phone
(301) 496-9423
Email
ferrarism@mail.nih.gov
First Name & Middle Initial & Last Name or Official Title & Degree
Robert B Innis, M.D.
Phone
(301) 594-1368
Email
robert.innis@nih.gov
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Robert B Innis, M.D.
Organizational Affiliation
National Institute of Mental Health (NIMH)
Official's Role
Principal Investigator
Facility Information:
Facility Name
National Institutes of Health Clinical Center
City
Bethesda
State/Province
Maryland
ZIP/Postal Code
20892
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
For more information at the NIH Clinical Center contact Office of Patient Recruitment (OPR)
Phone
800-411-1222
Ext
TTY8664111010
Email
prpl@cc.nih.gov

12. IPD Sharing Statement

Plan to Share IPD
Undecided
Links:
URL
https://clinicalstudies.info.nih.gov/cgi/detail.cgi?A_000483-M.html
Description
NIH Clinical Center Detailed Web Page

Learn more about this trial

PET Imaging of Cyclooxygenase-2 in Multiple Sclerosis

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