Trial Outcomes & Findings for Peripheral Benzodiazepine Receptors (PBR28) Brain PET Imaging With Lipopolysaccharide Challenge for the Study of Microglia Function in Alzheimer's Disease (NCT NCT04057807)

Last Updated: 2024-02-05

Results Overview

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.

Recruitment status

COMPLETED

Study phase

EARLY_PHASE1

Target enrollment

18 participants

Primary outcome timeframe

180 minutes post intervention

Results posted on

2024-02-05

Participant Flow

Participant milestones

Participant milestones
Measure	Patients Receiving Endotoxin The enrolled subjects will have LPS (0.4 ng/kg) administered intravenously LPS: LPS (0.4 ng/kg)
Overall Study STARTED	12
Overall Study 1 Week Follow up	11
Overall Study 6 Month Follow up	12
Overall Study COMPLETED	12
Overall Study NOT COMPLETED	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Baseline measures were collected by cognitive status.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Patients Receiving Endotoxin n=12 Participants The enrolled subjects, both with AD and cognitively normal, will have LPS (0.4 ng/kg) administered intravenously LPS: LPS (0.4 ng/kg)
Age, Continuous Alzheimer's Disease	75.3 years STANDARD_DEVIATION 2.3 • n=6 Participants • Baseline measures were collected by cognitive status.
Age, Continuous Cognitively Normal	67.2 years STANDARD_DEVIATION 6.5 • n=6 Participants • Baseline measures were collected by cognitive status.
Sex: Female, Male Alzheimer's Disease · Female	1 Participants n=6 Participants • Baseline measures were collected by cognitive status.
Sex: Female, Male Alzheimer's Disease · Male	5 Participants n=6 Participants • Baseline measures were collected by cognitive status.
Sex: Female, Male Cognitively Normal · Female	3 Participants n=6 Participants • Baseline measures were collected by cognitive status.
Sex: Female, Male Cognitively Normal · Male	3 Participants n=6 Participants • Baseline measures were collected by cognitive status.
Race/Ethnicity, Customized Alzheimer's Disease · White	6 Participants n=6 Participants • Baseline measures were collected by cognitive status.
Race/Ethnicity, Customized Alzheimer's Disease · Black	0 Participants n=6 Participants • Baseline measures were collected by cognitive status.
Race/Ethnicity, Customized Cognitively Normal · White	5 Participants n=6 Participants • Baseline measures were collected by cognitive status.
Race/Ethnicity, Customized Cognitively Normal · Black	1 Participants n=6 Participants • Baseline measures were collected by cognitive status.
Region of Enrollment United States	12 participants n=12 Participants
Global Clinical Dementia Rating Global Score (CDR) Alzheimer's Disease	0.75 score on a scale STANDARD_DEVIATION 0.27 • n=6 Participants • Baseline measures were collected by cognitive status.
Global Clinical Dementia Rating Global Score (CDR) Cognitively Normal	0 score on a scale STANDARD_DEVIATION 0 • n=6 Participants • Baseline measures were collected by cognitive status.
Montreal Cognitive Assessment (MOCA) Alzheimer's Disease	21.5 score on a scale STANDARD_DEVIATION 3.8 • n=6 Participants • Baseline measures were collected by cognitive status.
Montreal Cognitive Assessment (MOCA) Cognitively Normal	26.7 score on a scale STANDARD_DEVIATION 2.4 • n=6 Participants • Baseline measures were collected by cognitive status.
Number of participants with one of two rs6971 polymorphism Alzheimer's Disease · mixed affinity binder (MAB)	0 Participants n=6 Participants • Baseline measures were collected by cognitive status.
Number of participants with one of two rs6971 polymorphism Alzheimer's Disease · high affinity binder (HAB)	6 Participants n=6 Participants • Baseline measures were collected by cognitive status.
Number of participants with one of two rs6971 polymorphism Cognitively Normal · mixed affinity binder (MAB)	3 Participants n=6 Participants • Baseline measures were collected by cognitive status.
Number of participants with one of two rs6971 polymorphism Cognitively Normal · high affinity binder (HAB)	3 Participants n=6 Participants • Baseline measures were collected by cognitive status.

PRIMARY outcome

Timeframe: 180 minutes post intervention

Population: One participant from the cognitively normal group was excluded from this analysis since blood input function data for the baseline scan was inadequate for pharmacokinetic modeling.

Outcome measures

Outcome measures
Measure	Patients Receiving Endotoxin n=11 Participants The enrolled subjects will have LPS (0.4 ng/kg) administered intravenously LPS: LPS (0.4 ng/kg)
Microglial Activation Reserve Index (MARI) Alzheimer's Disease	17.7 percentage of MARI Standard Deviation 0.1
Microglial Activation Reserve Index (MARI) Cognitively Normal	30.1 percentage of MARI Standard Deviation 0.1

SECONDARY outcome

Timeframe: 180 minutes post intervention

Population: Data are from correlation between parietal cortex MARI and MOCA scores for participants with AD

The Pearson's correlation between MARI and performance on the Montreal Cognitive Assessment (MOCA) will be calculated. The MOCA is a global assessment of cognitive function ranging from 0 to 30 where higher scores represent better cognitive performance.

Outcome measures

Outcome measures
Measure	Patients Receiving Endotoxin n=6 Participants The enrolled subjects will have LPS (0.4 ng/kg) administered intravenously LPS: LPS (0.4 ng/kg)
Effects of MARI on Cognition	-0.12 Pearson r

Adverse Events

Patients Receiving Endotoxin

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Adverse event data not reported

Additional Information

Adam Mecca

Yale School of Medicine

Phone: 203.764.8100

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place