PET Imaging of Cyclooxygenases in Dementia

Overview

Background:

About 5 million adults in the U.S. have Alzheimer s disease or another adult-onset neurodegenerative disorder. Many studies have found that inflammation in the brain contributes to these diseases. Researchers want to find a better way to measure this inflammation.

Objective:

To learn if two new radiolabeled drugs, [11C]PS13 and [11C]MC1, can measure inflammation in the brain using positron emission tomography (PET) imaging.

Eligibility:

Adults age 18 years and older in good general health who have an adult-onset neurodegenerative dementia, and healthy adult volunteers enrolled in protocols 01-M-0254 or 17-M-0181

Design:

Participants will be screened with medical history, physical exam with vital signs, and lab tests. They will have a neurological exam and neuropsychological testing. Their heart function will be measured.

Participants will have a magnetic resonance imaging (MRI) scan. The MRI scanner is a metal tube surrounded by a strong magnetic field. Participants will lie on a table that slides in and out of the tube. The machine makes noise. Participants will get earplugs.

Participants will have 2 PET scans. They will be injected with the study drugs through an intravenous catheter placed in an arm vein. The PET scanner is shaped like a doughnut. Participants will lie on a bed that slides in and out of the scanner. A plastic mask will be molded to their head to keep them from moving. A thin plastic tube will be put into an artery at the wrist or elbow crease area. This will be used to draw blood during the scan.

Participants will have 2-3 study visits. Participation lasts 1 week to 4 months, depending on scheduling.

Full Title of Study: “Phase I Study: PET Imaging of Cyclooxygenases in Dementia”

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: N/A
    • Intervention Model: Single Group Assignment
    • Primary Purpose: Diagnostic
    • Masking: None (Open Label)
  • Study Primary Completion Date: January 16, 2023

Detailed Description

Study Description: This pilot/exploratory study will examine whether cyclooxygenase 1 (COX-1) and COX-2 are elevated in the brain of individuals with dementia compared to healthy volunteers.

Objectives: Primary Objective: To determine whether COX-1 or COX-2 is elevated in the brains of individuals with dementia compared to healthy volunteers.

Endpoints: Primary Endpoint: Measurement of COX-1 and COX-2 density in brain after PET scans with [11C]PS13 and [11C]MC1, respectively.

Study Population: Four groups of 16 subjects each will be studied: 1) Alzheimer s disease (AD), 2) frontotemporal dementia (FTD) 3) other dementias, and 4) healthy volunteers. Subjects may be male or female. They must be greater than or equal to 18 years old, but most are expected to be 60 to 80 years old. Subjects may be recruited from anywhere, but most are expected to come from the Washington DC metropolitan area. Patients must be in good medical health but may be unable to provide informed consent because of cognitive impairment. In that case, the Legally Appointed Representative (LAR) must provide consent, and the patient must provide assent.

Phase: 1

Description of Sites/Facilities Enrolling Participants: Screening and PET imaging will be performed at the NIH Clinical Center.

Description of Study Intervention:

Subjects will be intravenously injected with 20 mCi of each of two radioligands: [11C]MC1 and [11C]PS13. Subjects will also have a radial artery catheter(s) inserted to measure the concentration of radioligand (either one insertion (if both scans are performed on the same day) or two insertions (if the scans are performed on two different days). Subjects will also have a brain MRI to provide anatomic orientation for the PET scans.

Study Duration: 36 months

Participant Duration: One week to four months, depending on the patient s availability and access to MRI and PET cameras.

Interventions

  • Drug: 11C-MC1
    • Injected IV followed by PET scanning
  • Drug: 11C-PS13
    • Injected IV followed by PET scanning

Arms, Groups and Cohorts

  • Other: Only one arm
    • All subjects receive the same tests

Clinical Trial Outcome Measures

Primary Measures

  • Measure the concentration of radioligands
    • Time Frame: 1-2 days
    • Density of COX-1 and COX-2 in brain

Participating in This Clinical Trial

Inclusion Criteria

Patients: In order to be eligible to participate in this study, patients must meet all of the following criteria:

1. Be male or female, aged 18 or older.

2. Be able (or have their Legally Authorized Representative (LAR) be able) to understand the study and be willing to sign a written informed consent document.

3. Have been diagnosed by a neurologist or psychiatrist with an adult onset neurodegenerative dementia, such as AD, FTD, corticobasal syndrome, or Huntington s disease.

4. Be in good general health as evidenced by medical history and physical examination.

5. Have their radial artery pulse checked for the presence of adequate ulnar collateral flow and the absence of any metal or foreign objects in both wrists.

6. Agree to adhere to the lifestyle considerations.<TAB>

Healthy volunteers: In order to be eligible to participate in this study, healthy volunteer subjects must meet all of the following criteria:

1. Be male or female, aged 18 or older.

2. Be able to understand the study and be willing to sign a written informed consent document.

3. Be in good general health, as evidenced by medical history and physical examination, and have no cognitive impairment.

4. Be enrolled in 01-M-0254, The Evaluation of Participants with Mood and Anxiety Disorders and Healthy Volunteers (PI: Dr. Carlos Zarate) or 17-M-0181, Recruitment and Characterization of Healthy Research Volunteers for NIMH Intramural Studies (PI: Dr. Joyce Chung).

5. Have their radial artery pulse checked for the presence of adequate ulnar collateral flow and the absence of any metal or foreign objects in both wrists.

6. Agree to adhere to the lifestyle considerations.

Exclusion Criteria

Both patients and healthy volunteers who meet any of the following criteria will be excluded from participation in this study:

1. Clinically significant abnormalities on EKG or laboratory testing. 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); prothrombin and partial prothrombin tests; HIV blood test; and pregnancy test for women of childbearing potential.

2. Subjects should not have taken NSAIDs for two weeks prior to the PET scan. Aspirin, corticosteroids, or immunosuppressants (e.g. methotrexate) must not have been taken in the prior month.

3. 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.

4. Have an unstable medical condition that, in the opinion of the investigators, makes participation unsafe (e.g., an active infection or untreated malignancy).

5. Are unable to travel to the NIH.

6. 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.

7. 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.

8. Have a current drug or alcohol use disorder.

9. Are unable to have an MRI scan (e.g., because of 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, shrapnel fragments, or metal fragments in the eye).

10. Be NIMH staff or an NIH employee who is a subordinate/relative/co-worker of the investigators.

Gender Eligibility: All

Minimum Age: 18 Years

Maximum Age: N/A

Are Healthy Volunteers Accepted: Accepts Healthy Volunteers

Investigator Details

  • Lead Sponsor
    • National Institute of Mental Health (NIMH)
  • Provider of Information About this Clinical Study
    • Sponsor
  • Overall Official(s)
    • Robert B Innis, M.D., Principal Investigator, National Institute of Mental Health (NIMH)
  • Overall Contact(s)
    • Maria D Ferraris Araneta, C.R.N.P., (301) 496-9423, ferrarism@mail.nih.gov

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