11C-Acetate PET/CT Imaging As a Biomarker of Amyloid-Induced Neuroinflammation

Mild Cognitive Impairment Clinical Trial

Official title:

11C-Acetate Position Emission Tomography/Computerized Tomography (PET/CT) Imaging As a Biomarker of Amyloid-Induced Neuroinflammation

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02811744
• Other study ID #: 824822
• Status: Terminated
• Phase: Phase 2
• Start date: January 2017
• Est. completion date: February 28, 2022

Study information

• Verified date: January 2024
• Source: University of Pennsylvania
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The proposed study aims to use 11C-acetate position emission tomography/computed tomography (PET/CT) to preliminarily test and validate methods for imaging astrocyte activation as an early indicator of neuroinflammation in Alzheimer's disease (AD). 11C-Acetate PET/CT has been shown to quantify astrocyte activation in vivo, but no reports have evaluated its potential in AD. The investigators propose to test 11C-Acetate PET/CT as a marker for astrocyte activation associated with pathologic amyloid deposition in AD. The investigators will compare binding between subjects with early stage AD and healthy controls. Further, the investigators will investigate the correlation between amyloid and acetate binding. If the investigators find increased astrocyte activation in response to cerebral amyloid by showing a group difference in brain acetate uptake between disease and controls or a strong correlation between acetate and amyloid PET/CT binding. Validating neuroinflammation markers in AD ultimately may guide therapeutic modulation of beneficial and damaging neuroinflammation to slow disease progression, as well as providing new insights into AD pathophysiology.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 11
• Est. completion date: February 28, 2022
• Est. primary completion date: February 28, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 65 Years and older

Eligibility

Inclusion Criteria for amnestic MCI cohort:

1. Participants will be at least 65 years of age

2. Positive brain amyloid PET/CT scan within 6 months of study screening

3. Mini-mental status examination (MMSE) score = 24 at screening visit

4. A brain MRI is required. If a brain MRI has been performed within 6 months of 11C-Acetate PET/CT and of adequate quality that scan may be used for the study analysis, subjects who do not have a brain MRI will undergo a brain MRI as a part of this study

5. Participants must identify a study partner who is willing to accompany the patient to study visits

6. Participants must be informed of the investigational nature of this study and provide written informed consent in accordance with institutional and federal guidelines prior to study-specific procedures. If the patient is unable to provide informed consent, the patient's legal representative may consent on behalf of the patient but the patient will be asked to confirm assent.

Inclusion Criteria for Control cohort:

1. Participants will be at least 65 years of age

2. History of negative brain amyloid PET/CT scan within 6 months of study screening OR negative cerebrospinal fluid (CSF) analysis for AD biomarkers within 6 months of study screening

3. Mini-mental status examination (MMSE) > 27 at screening visit

4. A brain MRI is required. If a brain MRI has been performed within 6 months of enrollment to this study and of adequate quality that scan may be used for the study analysis, subjects who do not have a brain MRI will undergo a brain MRI as a part of this study

5. Participants must be informed of the investigational nature of this study and provide written informed consent in accordance with institutional and federal guidelines prior to study-specific procedures.

Exclusion Criteria for both cohorts:

1. Inability to tolerate or contraindication to imaging procedures (PET/CT or MRI) in the opinion of an investigator or treating physician

2. History of stroke or other neurological disease that in the opinion of the investigator might interfere with evaluation of the 11C-Acetate scan

3. Any medical or psychological conditions that, in the opinion of the investigator, would compromise the subject's safety or successful participation in the study.

Related Conditions & MeSH terms

• Cognitive Dysfunction
• Mild Cognitive Impairment

Intervention

Drug:
• 11C-acetate
Participants will receive injection of radioactive tracer 11C-acetate and complete a PET/CT scan.

Locations

Country	Name	City	State
United States	University of Pennsylvania	Philadelphia	Pennsylvania

Sponsors (1)

Lead Sponsor	Collaborator
University of Pennsylvania

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	11C-acetate Uptake in Amyloid Positive Mild Cognitive Impairment (MCI) Subjects Versus Amyloid Negative Healthy Controls	We compare the whole brain 11C-acetate uptake standardized uptake value ratio (SUVR) between the amnestic MCI and control cohorts. Static summed images from 40-60 minutes after tracer injection were generated from raw dynamic PET data. This timeframe was selected to preferentially capture 11C-acetate trapped in biosynthetic pathways in activated astrocytes, rather than what was catabolized to 11C-CO2 .Mean tracer binding, expressed as standardized uptake values (SUV) in the whole cerebral cortex and other regions is measured from these summed images using PMOD software (PMOD technologies). SUVR is generated by dividing the mean whole cortex SUV by the mean cerebellar gray matter SUV; SUVR is a unitless measure. For this tracer, higher values are worse, indicating more astrocyte activation and inflammation.	6 months