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

NCT02811744 | Terminated Phase 2 Results

• 1 other identifier: 824822
• Study Type: interventional
• Target: 11
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Mild Cognitive Impairment

Outcome Measures

Primary Outcomes (1)

• 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

Study Arms (2)

Amnestic MCI cohort

EXPERIMENTAL

Patients with Mild Cognitive Impairment (MCI) (up to 14) will be recruited primarily from the Penn Memory Center (PMC). Clinical diagnostic criteria (described in further detail in Study Procedures section) will be used to identify subjects who are meet criteria for amnestic MCI. Participants will receive injection of radioactive tracer 11C-acetate and complete a PET/CT scan.

Drug: 11C-acetate

Control cohort

OTHER

Normal control subjects in the same age range (up to 6) will be recruited from a current ongoing study investigating neuroinflammation in late life depression and healthy controls, from the control group in which all subjects receive MRI and lumbar puncture (LP) and from the PMC research cohort. Participants will receive injection of radioactive tracer 11C-acetate and complete a PET/CT scan.

Drug: 11C-acetate

Interventions

11C-acetate DRUG

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

Amnestic MCI cohort; Control cohort

Eligibility Criteria

• Age: 65 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Older Adult (65+)

You may qualify if:

• Participants will be at least 65 years of age
• Positive brain amyloid PET/CT scan within 6 months of study screening
• Mini-mental status examination (MMSE) score ≥ 24 at screening visit
• 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
• Participants must identify a study partner who is willing to accompany the patient to study visits
• 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.
• Participants will be at least 65 years of age
• 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
• Mini-mental status examination (MMSE) \> 27 at screening visit
• 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
• 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.

You may not qualify if:

• Inability to tolerate or contraindication to imaging procedures (PET/CT or MRI) in the opinion of an investigator or treating physician
• History of stroke or other neurological disease that in the opinion of the investigator might interfere with evaluation of the 11C-Acetate scan
• Any medical or psychological conditions that, in the opinion of the investigator, would compromise the subject's safety or successful participation in the study.

Sponsors & Collaborators

• University of Pennsylvania: lead

Study Sites (1)

University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

MeSH Terms

Conditions

Cognitive Dysfunction

Interventions

carbon-11 acetate

Condition Hierarchy (Ancestors)

Cognition Disorders; Neurocognitive Disorders; Mental Disorders

Results Point of Contact

• Title: Erin Schubert
• Organization: Univerisity of Pennsylvania

erin.schubert@pennmedicine.upenn.edu

215-573-6569

Study Officials

• Ilya Nasrallah, MD

  University of Pennsylvania

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 20, 2016
• First Posted: June 23, 2016
• Study Start: January 1, 2017
• Primary Completion: February 28, 2022
• Study Completion: February 28, 2022
• Last Updated: January 11, 2024
• Results First Posted: January 11, 2024

Record last verified: 2024-01

Locations

US (1)