Peripheral Benzodiazepine Receptors (PBR28) Brain PET Imaging With Lipopolysaccharide Challenge for the Study of Microglia Function in Alzheimer's Disease

NCT04057807 | Completed Early Phase 1 Results FDA Drug

• 2 other identifiers: 16110186111K23AG057794-01
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

Brief Summary

To examine the differences in the capacity to activate microglia in patients with Alzheimer's Disease (AD) compared to age-comparable cognitively normal subjects and younger healthy controls.

Conditions

Alzheimer Disease

Outcome Measures

Primary Outcomes (1)

• Microglial Activation Reserve Index (MARI)

  Participants will undergo \[11C\]PBR PET scanning both before and then after LPS injection. Parametric images of volume of distribution (VT)were generated for each using multilinear analysis (MA1) and MARI was calculated in the parietal cortex using the equation \[(VT post LPS - VT pre LPS)/VT post LPS\] x 100%. Higher values of MARI are thought to represent higher levels of microglial activation. There are no clinically relevant thresholds for this measure.

  180 minutes post intervention

Secondary Outcomes (1)

• Effects of MARI on Cognition

  180 minutes post intervention

Study Arms (1)

Patients receiving endotoxin

EXPERIMENTAL

The 20 enrolled subjects will have LPS (0.4 ng/kg) administered intravenously

Drug: LPS

Interventions

LPS DRUG

LPS (0.4 ng/kg)

Patients receiving endotoxin

Eligibility Criteria

• Age: 55 Years - 90 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Mild AD Subjects:
• National Institute on Aging (NIA)-Alzheimer's Association core clinical criteria for probable AD
• Age between 55 and 90 (inclusive)
• Score on the Montreal Cognitive Assessment (MOCA) greater than or equal to 17
• Presence of a responsible caregiver who will accompany AD subjects to all procedures.
• Biomarker evidence of Alzheimer's disease via an amyloid PET scan or cerebrospinal fluid (CSF) amyloid Beta measurement.
• The patient should have the capacity to consent.
• Clinical Dementia Rating (CDR) global score greater than 0.
• Cognitively normal elderly Subjects:
• Absence of National Institute on Aging-Alzheimer's Association core clinical criteria for probable AD
• Objective memory scores within the normal range for age (do not meet MCI Subjects criterion 2)
• Age between 55 and 90 (inclusive)
• Clinical Dementia Rating (CDR) global score of 0.0

You may not qualify if:

• Any significant neurologic disease (other than probable AD in the AD Subjects group), such as stroke, Parkinson's disease, brain tumor, seizure disorder, multiple sclerosis, or history of significant head trauma followed by persistent neurologic deficits.
• Any significant systemic disease including hepatic failure, heart failure, renal failure, chronic obstructive pulmonary disease (COPD), active infection and autoimmune disease.
• Screening/baseline MRI scan with evidence of infection, infarction, or other focal lesions. Subjects with multiple lacunes or lacunes in a critical memory structure are excluded.
• Any significant systemic illness or unstable medical condition, including uncontrolled or insulin- dependent diabetes mellitus, uncorrected hypothyroidism or hyperthyroidism, or systemic cancer.
• Current or regular use of over-the-counter medication that may affect the immune system (e.g., ibuprofen), including corticosteroids or immunosuppressant drugs; no use in 3 weeks prior to the PET scan
• Investigational agents are prohibited 4 weeks prior to entry and for the duration of the study.
• Previous treatment with an investigational small molecule with anti-amyloid properties or passive immunization against amyloid within 1 year of study entry.
• Previous treatment with an active immunization against amyloid.
• History of schizophrenia or other major psychiatric disorder (DSM IV criteria).
• History of alcohol or substance abuse or dependence (DSM IV criteria) within the past 2 years.
• Clinically significant abnormalities on screening laboratory tests (B12, Thyroid function tests, hematology, chemistry, urinalysis, ECG).
• Pregnancy, as determined by screening pregnancy tests for pre-menopausal females
• Impairment of visual or auditory acuity sufficient to interfere with study procedures.
• Education level \< 6 years.
• Evidence of current depression as defined by a score of ≥ 5 on the Geriatric Depression Scale.

Sponsors & Collaborators

• Yale University: lead
• National Institute on Aging (NIA): collaborator

Study Sites (1)

Alzheimer's Disease Research Unit

New Haven, Connecticut, 06510, United States

Location

MeSH Terms

Conditions

Alzheimer Disease

Condition Hierarchy (Ancestors)

Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases; Neurocognitive Disorders; Mental Disorders

Results Point of Contact

• Title: Adam Mecca
• Organization: Yale School of Medicine

adam.mecca@yale.edu

203.764.8100

Study Officials

• Adam Mecca, M.D., Ph.D.

  Yale University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 13, 2019
• First Posted: August 15, 2019
• Study Start: April 15, 2018
• Primary Completion: July 27, 2022
• Study Completion: July 27, 2022
• Last Updated: February 5, 2024
• Results First Posted: October 18, 2023

Record last verified: 2024-02

Locations

US (1)