Trial Outcomes & Findings for Measuring the Neuroimmune Response to Alcohol (NCT NCT04251221)
NCT ID: NCT04251221
Last Updated: 2023-11-07
Results Overview
This is the percent change in \[11C\]PBR28 distribution volume (V\_T) post-alcohol relative to baseline. This is calculated as \[V\_T(Post-Alcohol) - V\_T(Baseline)\]/V\_T(Baseline) As a percent change, it could range from -10% to 200%.
Recruitment status
COMPLETED
Study phase
EARLY_PHASE1
Target enrollment
14 participants
Primary outcome timeframe
The post-alcohol imaging scan start will begin between one and fours hours after the oral alcohol challenge is completed. The total scan time for each imaging scan is 120 minutes long.
Results posted on
2023-11-07
Participant Flow
Participant milestones
| Measure |
Moderate Drinkers
Aim 1:
A baseline PET scan with \[11C\]PBR28, a TSPO-specific radioligand, will be conducted with moderate drinkers. Next, subjects will drink a fixed alcohol dose, followed a post-alcohol \[11C\]PBR28 PET scan timed to capture acute neuroimmune response. \[11C\]PBR28 distribution volumes (VT), which are proportional to TSPO number, will be measured throughout the brain. We will test the hypothesis that acute alcohol robustly increases \[11C\]PBR28 VT, consistent with microglial activation. The percent change in \[11C\]PBR28 VT (ΔVT) from baseline will quantify the magnitude of neuroimmune response.
Oral Alcohol Challenge: Subjects will drink an alcohol dose designed to achieve a BAL of 0.08
|
Alcohol Use Disorder (AUD)
Aim 2:
AUD subjects will participate in the study design described in Aim 1 (a baseline \[11C\]PBR28 PET scan, drink a fixed alcohol dose, followed by a post-alcohol \[11C\]PBR28 PET scans). The magnitude of neuroimmune response, quantified by ΔVT, will be compared between moderate drinkers and individuals with AUD to test the hypothesis that the neuroimmune response to alcohol is greater in those with AUD compared to moderate drinkers, consistent with the concept of alcohol 'priming microglia'.
Oral Alcohol Challenge: Subjects will drink an alcohol dose designed to achieve a BAL of 0.08
|
|---|---|---|
|
Overall Study
STARTED
|
11
|
3
|
|
Overall Study
COMPLETED
|
9
|
3
|
|
Overall Study
NOT COMPLETED
|
2
|
0
|
Reasons for withdrawal
| Measure |
Moderate Drinkers
Aim 1:
A baseline PET scan with \[11C\]PBR28, a TSPO-specific radioligand, will be conducted with moderate drinkers. Next, subjects will drink a fixed alcohol dose, followed a post-alcohol \[11C\]PBR28 PET scan timed to capture acute neuroimmune response. \[11C\]PBR28 distribution volumes (VT), which are proportional to TSPO number, will be measured throughout the brain. We will test the hypothesis that acute alcohol robustly increases \[11C\]PBR28 VT, consistent with microglial activation. The percent change in \[11C\]PBR28 VT (ΔVT) from baseline will quantify the magnitude of neuroimmune response.
Oral Alcohol Challenge: Subjects will drink an alcohol dose designed to achieve a BAL of 0.08
|
Alcohol Use Disorder (AUD)
Aim 2:
AUD subjects will participate in the study design described in Aim 1 (a baseline \[11C\]PBR28 PET scan, drink a fixed alcohol dose, followed by a post-alcohol \[11C\]PBR28 PET scans). The magnitude of neuroimmune response, quantified by ΔVT, will be compared between moderate drinkers and individuals with AUD to test the hypothesis that the neuroimmune response to alcohol is greater in those with AUD compared to moderate drinkers, consistent with the concept of alcohol 'priming microglia'.
Oral Alcohol Challenge: Subjects will drink an alcohol dose designed to achieve a BAL of 0.08
|
|---|---|---|
|
Overall Study
Arterial Line Failure, unable to proceed with PET scan
|
2
|
0
|
Baseline Characteristics
Measuring the Neuroimmune Response to Alcohol
Baseline characteristics by cohort
| Measure |
Moderate Drinkers
n=11 Participants
Aim 1:
A baseline PET scan with \[11C\]PBR28, a TSPO-specific radioligand, will be conducted with moderate drinkers. Next, subjects will drink a fixed alcohol dose, followed a post-alcohol \[11C\]PBR28 PET scan timed to capture acute neuroimmune response. \[11C\]PBR28 distribution volumes (VT), which are proportional to TSPO number, will be measured throughout the brain. We will test the hypothesis that acute alcohol robustly increases \[11C\]PBR28 VT, consistent with microglial activation. The percent change in \[11C\]PBR28 VT (ΔVT) from baseline will quantify the magnitude of neuroimmune response.
Oral Alcohol Challenge: Subjects will drink an alcohol dose designed to achieve a BAL of 0.08
|
Alcohol Use Disorder (AUD)
n=3 Participants
Aim 2:
AUD subjects will participate in the study design described in Aim 1 (a baseline \[11C\]PBR28 PET scan, drink a fixed alcohol dose, followed by a post-alcohol \[11C\]PBR28 PET scans). The magnitude of neuroimmune response, quantified by ΔVT, will be compared between moderate drinkers and individuals with AUD to test the hypothesis that the neuroimmune response to alcohol is greater in those with AUD compared to moderate drinkers, consistent with the concept of alcohol 'priming microglia'.
Oral Alcohol Challenge: Subjects will drink an alcohol dose designed to achieve a BAL of 0.08
|
Total
n=14 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
|
Age, Continuous
|
30.36 years
STANDARD_DEVIATION 7.84 • n=99 Participants
|
34.33 years
STANDARD_DEVIATION 7.76 • n=107 Participants
|
31.21 years
STANDARD_DEVIATION 7.99 • n=206 Participants
|
|
Sex: Female, Male
Female
|
6 Participants
n=99 Participants
|
1 Participants
n=107 Participants
|
7 Participants
n=206 Participants
|
|
Sex: Female, Male
Male
|
5 Participants
n=99 Participants
|
2 Participants
n=107 Participants
|
7 Participants
n=206 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
5 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
5 Participants
n=206 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
6 Participants
n=99 Participants
|
3 Participants
n=107 Participants
|
9 Participants
n=206 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
|
Race (NIH/OMB)
Black or African American
|
2 Participants
n=99 Participants
|
1 Participants
n=107 Participants
|
3 Participants
n=206 Participants
|
|
Race (NIH/OMB)
White
|
9 Participants
n=99 Participants
|
2 Participants
n=107 Participants
|
11 Participants
n=206 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
|
rs6971 Genotype
High Affinity Binder (HAB)
|
10 Participants
n=99 Participants
|
1 Participants
n=107 Participants
|
11 Participants
n=206 Participants
|
|
rs6971 Genotype
Mixed Affinity Binder (MAB)
|
1 Participants
n=99 Participants
|
2 Participants
n=107 Participants
|
3 Participants
n=206 Participants
|
|
rs6971 Genotype
Low Affinity Binder (LAB)
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
PRIMARY outcome
Timeframe: The post-alcohol imaging scan start will begin between one and fours hours after the oral alcohol challenge is completed. The total scan time for each imaging scan is 120 minutes long.Population: The ten participants (7M, 3F; 3 Mild AUD) who completed the laboratory drinking session were included in whole-body PET and cytokine data analysis.
This is the percent change in \[11C\]PBR28 distribution volume (V\_T) post-alcohol relative to baseline. This is calculated as \[V\_T(Post-Alcohol) - V\_T(Baseline)\]/V\_T(Baseline) As a percent change, it could range from -10% to 200%.
Outcome measures
| Measure |
Moderate Drinkers
n=7 Participants
Aim 1:
A baseline PET scan with \[11C\]PBR28, a TSPO-specific radioligand, will be conducted with moderate drinkers. Next, subjects will drink a fixed alcohol dose, followed a post-alcohol \[11C\]PBR28 PET scan timed to capture acute neuroimmune response. \[11C\]PBR28 distribution volumes (VT), which are proportional to TSPO number, will be measured throughout the brain. We will test the hypothesis that acute alcohol robustly increases \[11C\]PBR28 VT, consistent with microglial activation. The percent change in \[11C\]PBR28 VT (ΔVT) from baseline will quantify the magnitude of neuroimmune response.
Oral Alcohol Challenge: Subjects will drink an alcohol dose designed to achieve a BAL of 0.08
|
Alcohol Use Disorder (AUD)
n=3 Participants
Aim 2:
AUD subjects will participate in the study design described in Aim 1 (a baseline \[11C\]PBR28 PET scan, drink a fixed alcohol dose, followed by a post-alcohol \[11C\]PBR28 PET scans). The magnitude of neuroimmune response, quantified by ΔVT, will be compared between moderate drinkers and individuals with AUD to test the hypothesis that the neuroimmune response to alcohol is greater in those with AUD compared to moderate drinkers, consistent with the concept of alcohol 'priming microglia'.
Oral Alcohol Challenge: Subjects will drink an alcohol dose designed to achieve a BAL of 0.08
|
|---|---|---|
|
Percent Change in [11C]PBR28 Distribution Volume After Alcohol Challenge.
|
15.79 [11C]PBR28 VT (% change)
Standard Deviation 8.00
|
6.36 [11C]PBR28 VT (% change)
Standard Deviation 1.27
|
Adverse Events
Moderate Drinkers
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Alcohol Use Disorder (AUD)
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
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place