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Neuroinflammation Imaging in AD

Primary Purpose

Alzheimer Disease, Healthy Volunteer

Status
Recruiting
Phase
Early Phase 1
Locations
United States
Study Type
Interventional
Intervention
[18F]NOS
[11C]PBR28
Sponsored by
University of Pennsylvania
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional other trial for Alzheimer Disease

Eligibility Criteria

55 Years - undefined (Adult, Older Adult)All SexesAccepts Healthy Volunteers

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

Sites / Locations

  • University of PennsylvaniaRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

AD/MCI or HC

AD/MCI or HC with Genetic Polymorphism

Arm Description

Main Study: Subjects are diagnosed with Alzheimer's Disease (AD)/Mild Cognitive Imparment (MCI) or are healthy volunteers/controls (HC).

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).

Outcomes

Primary Outcome Measures

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.
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

Secondary Outcome Measures

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
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

Full Information

First Posted
February 12, 2020
Last Updated
May 31, 2023
Sponsor
University of Pennsylvania
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1. Study Identification

Unique Protocol Identification Number
NCT04274998
Brief Title
Neuroinflammation Imaging in AD
Official Title
Evaluation of in Vivo Neuroinflammation in Alzheimer's Disease Using Novel Positron Emission Tomography (PET/CT) Imaging
Study Type
Interventional

2. Study Status

Record Verification Date
May 2023
Overall Recruitment Status
Recruiting
Study Start Date
March 3, 2020 (Actual)
Primary Completion Date
March 1, 2025 (Anticipated)
Study Completion Date
March 1, 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of Pennsylvania

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
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Alzheimer Disease, Healthy Volunteer

7. Study Design

Primary Purpose
Other
Study Phase
Early Phase 1
Interventional Study Model
Sequential Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
20 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
AD/MCI or HC
Arm Type
Experimental
Arm Description
Main Study: Subjects are diagnosed with Alzheimer's Disease (AD)/Mild Cognitive Imparment (MCI) or are healthy volunteers/controls (HC).
Arm Title
AD/MCI or HC with Genetic Polymorphism
Arm Type
Experimental
Arm Description
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).
Intervention Type
Drug
Intervention Name(s)
[18F]NOS
Intervention Description
Main Study: PET/CT imaging will be used to evaluate neuroinflammation in the brain using the investigational radiotracer [18F]NOS.
Intervention Type
Drug
Intervention Name(s)
[11C]PBR28
Intervention Description
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.
Primary Outcome Measure Information:
Title
Understanding the uptake of [18F]NOS in the human brain in AD/MCI and Healthy Controls
Description
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.
Time Frame
3 years
Title
Comparing the patterns of [18F]NOS brain uptake with patterns of cerebral amyloidosis and neurodegeneration using PET/CT
Description
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
Time Frame
3 years
Secondary Outcome Measure Information:
Title
Understanding the uptake of [11C]PBR28 in the human brain in AD/MCI and Healthy Controls with a specific genetic polymorphism
Description
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
Time Frame
3 years
Title
Comparing the patterns of [11C]PBR28 brain uptake with patterns of cerebral amyloidosis and neurodegeneration using PET/CT
Description
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
Time Frame
3 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
55 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria (HC cohort only): - Males and females ≥ 55 years of age Part of the UPenn ADC research cohort with designation of cognitively normal per ADC database. A brain amyloid PET scan ≤ 1 year prior to enrollment in this study that is determined to be negative by the study PI. Mini-mental status exam (MMSE) score of 28 or higher per ADC database. 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) Males and females ≥ 55 years of age Part of the Upenn ADC research cohort with designation that the presence of Alzheimer's pathology is likely per ADC database. A brain amyloid PET scan ≤ 1 year prior to enrollment in this study that is determined to be positive by the study PI. Mini-mental status exam (MMSE) score of 14-27 per ADC database. 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): Females of child-bearing potential will not be included, female subjects must be post-menopausal or surgically sterile History of epilepsy or seizure disorder as assessed by medical record review and/or self-report 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 Current tobacco or nicotine dependence. History of greater than 5 pack years of smoking and less than 2 years since smoking cessation. Have a history of significant or ongoing alcohol abuse or substance abuse or dependence based on medical record review or self-reported Inability to tolerate imaging procedures in the opinion of an investigator or treating physician 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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Erin Schubert
Phone
215-573-6569
Email
erinschu@pennmedicine.upenn.edu
First Name & Middle Initial & Last Name or Official Title & Degree
IIya Nasrallah, MD
Email
IIya.Nasrallah@pennmedicine.upenn.edu
Facility Information:
Facility Name
University of Pennsylvania
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19104
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Erin Schubert
Phone
215-573-6569
Email
erinschu@pennmedicine.upenn.edu

12. IPD Sharing Statement

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Neuroinflammation Imaging in AD

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