Neuroinflammation Imaging in AD

Evaluation of in Vivo Neuroinflammation in Alzheimer's Disease Using Novel Positron Emission Tomography (PET/CT) Imaging

This research study is being done to learn more about inflammation in the brain using Positron Emission Tomography/Computed Tomography (PET/CT) imaging in people with Alzheimer's Disease/Mild Cognitive Impairment or healthy controls.

If the subject agrees to be in this study, she/ he will have a PET/CT scan using the investigational radiotracer [18F]NOS. A subject with a specific genetic polymorphism may also agree to be in the sub-study in which she/he will have another PET/CT scan using the investigational tracer [11C]PBR28 for comparison with the FNOS [18F]NOS scan. For subjects who agree to this sub-study they may undergo the brain PET/CT scan with [11C]PBR28 either on the same day as the [18F]NOS PET/CT or on another day. The subject may have a screening visit before the PET/CT scan visit if the investigator needs to confirm the subject is able to be in the study.

A blood sample will be taken before the scans. Additional blood samples will be taken during the PET scans. Subjects must also agree to have an MRI scan for this research study if she/he has not had a recent scan that the study doctor decides can be used for this study.

Study Overview

• Status: Recruiting
• Conditions: Alzheimer Disease; Healthy Volunteer
• Intervention / Treatment: Drug: [18F]NOS; Drug: [11C]PBR28

• Study Type: Interventional
• Enrollment (Estimated): 20
• Phase: Early Phase 1

Contacts and Locations

• Study Contact: Name: IIya Nasrallah, MD; Email: IIya.Nasrallah@pennmedicine.upenn.edu
• Study Contact Backup: Name: Erin Schubert; Phone Number: 215-573-6569; Email: erinschu@pennmedicine.upenn.edu

Study Locations

• United States
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Recruiting
      • University of Pennsylvania
      • Contact: Erin Schubert; Phone Number: 215-573-6569; Email: erinschu@pennmedicine.upenn.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 55 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria (HC cohort only):

1. - Males and females ≥ 55 years of age
2. Part of the UPenn ADC research cohort with designation of cognitively normal per ADC database.
3. A brain amyloid PET scan ≤ 1 year prior to enrollment in this study that is determined to be negative by the study PI.
4. Mini-mental status exam (MMSE) score of 28 or higher per ADC database.
5. Participants must be informed of the investigational nature of this study and be willing to provide written informed consent and participate in this study in accordance with institutional and federal guidelines prior to study-specific procedures.

Inclusion Criteria (AD/MCI cohort only)

1. Males and females ≥ 55 years of age
2. Part of the Upenn ADC research cohort with designation that the presence of Alzheimer's pathology is likely per ADC database.
3. A brain amyloid PET scan ≤ 1 year prior to enrollment in this study that is determined to be positive by the study PI.
4. Mini-mental status exam (MMSE) score of 14-27 per ADC database.
5. Subjects must have a designated study partner to accompany them to study visits

Inclusion Criteria 11C-PBR28 sub-study (both HC and AD/MCI cohorts)

1. High affinity carrier of the rs6971 TSPO polymorphism (whole genome sequencing is available from the UPenn ADC research cohort and will be interrogated for this polymorphism)

Exclusion Criteria (HC and PD cohorts):

1. Females of child-bearing potential will not be included, female subjects must be post-menopausal or surgically sterile
2. History of epilepsy or seizure disorder as assessed by medical record review and/or self-report
3. History of head trauma or evidence of structural abnormalities such as a major stroke or mass on MRI that in the opinion of an investigator may interfere with the uptake of applicable radiotracer as assessed by medical record review and/or self-report
4. Current tobacco or nicotine dependence. History of greater than 5 pack years of smoking and less than 2 years since smoking cessation.
5. Have a history of significant or ongoing alcohol abuse or substance abuse or dependence based on medical record review or self-reported
6. Inability to tolerate imaging procedures in the opinion of an investigator or treating physician
7. Any current medical condition, illness, or disorder as assessed by medical record review and/or self-reported that is considered by a physician or investigator to be a condition that could compromise participant safety or successful participation in the study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: AD/MCI or HC; Main Study: Subjects are diagnosed with Alzheimer's Disease (AD)/Mild Cognitive Imparment (MCI) or are healthy volunteers/controls (HC).	Drug: [18F]NOS; Main Study: PET/CT imaging will be used to evaluate neuroinflammation in the brain using the investigational radiotracer [18F]NOS.
Experimental: AD/MCI or HC with Genetic Polymorphism; Sub-Study: Subjects have a specific genetic polymorphism andare diagnosed with Alzheimer's Disease (AD)/Mild Cognitive Imparment (MCI) or are healthy volunteers/controls (HC).	Drug: [11C]PBR28; Sub-Study: Additional PET/CT imaging will be used to evaluate neuroinflammation in the brain for subjects with specific genetic polymorphism using the investigational radiotracer [11C]PBR28 in comparison to [18F]NOS.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Understanding the uptake of [18F]NOS in the human brain in AD/MCI and Healthy Controls	This main study outcome measure will be comparison of whole brain GM binding between controls and the MCI/AD group. the investigator will compare groups with a t-test. the investigator will evaluate the correlation of whole brain GM binding of 18F-NOS.	3 years
Comparing the patterns of [18F]NOS brain uptake with patterns of cerebral amyloidosis and neurodegeneration using PET/CT	This main study outcome measure will include regional and voxel-wise comparisons between binding of the tracers. Correlation between regional 18F-NOS binding and either amyloid PET SUVR (calculated with cerebellar gray matter reference) or GM volumetric measurements will be evaluated using Pearson's r and rank sum correlation initially using false discovery rate (FDR)-corrected<0.05 statistical thresholds	3 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Understanding the uptake of [11C]PBR28 in the human brain in AD/MCI and Healthy Controls with a specific genetic polymorphism	This sub-study outcome measure will be comparison of whole brain GM binding between controls and the MCI/AD group. the investigator will compare groups with a t-test. the investigator will evaluate the correlation of whole brain GM binding of 11C-PBR28	3 years
Comparing the patterns of [11C]PBR28 brain uptake with patterns of cerebral amyloidosis and neurodegeneration using PET/CT	This sub-study outcome measure will include regional and voxel-wise comparisons between binding of the tracers. Correlation between regional 11C-PBR28 binding and either amyloid PET SUVR (calculated with cerebellar gray matter reference) or GM volumetric measurements will be evaluated using Pearson's r and rank sum correlation initially using false discovery rate (FDR)-corrected<0.05 statistical thresholds	3 years

Collaborators and Investigators

• Sponsor: University of Pennsylvania

Study record dates

Study Major Dates

• Study Start (Actual): March 3, 2020
• Primary Completion (Estimated): March 1, 2025
• Study Completion (Estimated): March 1, 2025

Study Registration Dates

• First Submitted: February 12, 2020
• First Submitted That Met QC Criteria: February 14, 2020
• First Posted (Actual): February 19, 2020

Study Record Updates

• Last Update Posted (Actual): June 1, 2023
• Last Update Submitted That Met QC Criteria: May 31, 2023
• Last Verified: May 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Pathologic Processes; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Inflammation; Neurocognitive Disorders; Neurodegenerative Diseases; Dementia; Tauopathies; Alzheimer Disease; Neuroinflammatory Diseases
• Other Study ID Numbers: 834090

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No