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| ID | Type | Description | Link |
|---|---|---|---|
| 1U54AA027989-01 | U.S. NIH Grant/Contract | View source |
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| Name | Class |
|---|---|
| National Institute on Alcohol Abuse and Alcoholism (NIAAA) | NIH |
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This study uses positron emission tomography imaging of the 18-kDa translocator protein to measure the brain's immune response to alcohol.
Alcohol Use Disorder affects nearly 14% of the population, accruing considerable cost to individual families and society. Much of this cost stems from alcohol's influence on the immune system. Alcohol impairs peripheral immune function, evidenced by increased susceptibility to infection related diseases such as liver cirrhosis and pancreatitis. The neuroimmune consequences of alcohol are subtler. Preclinically, alcohol triggers neuroimmune abnormalities that contribute to cognitive dysfunction, neurodegeneration, and alter alcohol drinking behaviors. Yet, limited experimental tools hamper translational efforts to study alcohol's effects on neuroimmune function in people. We propose to address this deficit by developing an innovative human imaging paradigm that measures neuroimmune response to alcohol.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Moderate Drinkers | Experimental | 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. |
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| Alcohol Use Disorder (AUD) | Experimental | 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'. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Oral Alcohol Challenge | Drug | Subjects will drink an alcohol dose designed to achieve a BAL of 0.08 |
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| Measure | Description | Time Frame |
|---|---|---|
| Percent Change in [11C]PBR28 Distribution Volume After Alcohol Challenge. | 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%. | 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. |
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General Inclusion Criteria:
General Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Ansel T Hillmer, Ph.D. | Yale University | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Yale University | New Haven | Connecticut | 06511 | United States |
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| ID | Title | Description |
|---|---|---|
| FG000 | 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 |
| FG001 | 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 |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
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Moderate Drinkers will self-report drinking consistent with at least one binge alcohol event in the past three months but will not meet DSM-5 criteria for AUD to ensure that accustomed drinking levels are not exceeded in the laboratory. AUD subjects will meet DSM-5 criteria for current Alcohol Use Disorder.
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| ID | Title | Description |
|---|---|---|
| BG000 | 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 |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Percent Change in [11C]PBR28 Distribution Volume After Alcohol Challenge. | 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%. | The ten participants (7M, 3F; 3 Mild AUD) who completed the laboratory drinking session were included in whole-body PET and cytokine data analysis. | Posted | Mean | Standard Deviation | [11C]PBR28 VT (% change) | 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. |
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1 Month After Study Day
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | 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 |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Ansel Hillmer | Yale University | 203-737-6400 | ansel.hillmer@yale.edu |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Aug 11, 2021 | Sep 18, 2023 | Prot_SAP_000.pdf |
| ICF | No | No | Yes | Informed Consent Form | Oct 13, 2021 | Sep 18, 2023 | ICF_001.pdf |
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| ID | Term |
|---|---|
| D000428 | Alcohol Drinking |
| ID | Term |
|---|---|
| D004327 | Drinking Behavior |
| D001519 | Behavior |
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| ID | Term |
|---|---|
| D000431 | Ethanol |
| ID | Term |
|---|---|
| D000438 | Alcohols |
| D009930 | Organic Chemicals |
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| BG001 | 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 |
| BG002 | Total | Total of all reporting groups |
| years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Ethnicity (NIH/OMB) | Count of Participants | Participants |
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| Race (NIH/OMB) | Count of Participants | Participants |
|
| rs6971 Genotype | This rs6971 genotype is a well-characterized polymorphism that directly affects the radiotracer affinity for the TSPO site. Study participants are prospectively genotyped. Low Affinity Binders (LAB, homozygotes for the minor allele, ~10% of the population) are excluded due to limited image quality. MAB or HAB status is included as a fixed factor in final statistical analyses. | Count of Participants | Participants |
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| OG001 | 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 |
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| 0 |
| 11 |
| 0 |
| 11 |
| 0 |
| 11 |
| EG001 | 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 | 0 | 3 | 0 | 3 | 0 | 3 |
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