Brain Inflammation and Function in Alcoholism
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|ClinicalTrials.gov Identifier: NCT02233868|
Recruitment Status : Recruiting
First Posted : September 9, 2014
Last Update Posted : March 1, 2018
- Brain inflammation due to high alcohol intake may affect thinking, memory, and concentration. Researchers want to measure this using positron emission tomography (PET).
- To study how excessive alcohol consumption affects brain function.
- Adults 30-75 years old who are moderate or severe alcohol drinkers.
- Healthy volunteers.
- Participants will be screened with medical history, physical exam, interview, and blood and urine tests. Their breath will be tested for alcohol and recent smoking.
- Phase 1:
- Participants will stay in the hospital 3 days. They will have blood and heart tests and daily urine tests.
- A small plastic tube will be inserted by needle in each arm. One will go in a vein, the other in an artery.
- Participants will have 2 PET scans with 2 different radioactive compounds. Participants will lie on a bed that slides in and out of the scanner with a cap on their head.
- Participants will have magnetic resonance imaging (MRI) scans. Participants will lie in the scanner either resting with their eyes open or while performing an attention task.
- Participants will have tests of memory, attention, concentration, and thinking. They may answer questions, take tests, and perform simple actions.
- Phase 2 of the study will only be done if Phase 1 results show brain inflammation.
- Phase 2 will repeat Phase 1.
- For healthy volunteers, Phase 2 will begin 3 weeks after Phase 1.
- Other volunteers must not have alcohol for at least 3 weeks and stay in a hospital up to 4-6 weeks between Phase 1 and Phase 2. After Phase 2, they will have 5 follow-up calls over 3 months.
|Condition or disease||Intervention/treatment||Phase|
|Alcoholism||Device: MRI Drug: C-11PBR28 Drug: F-18FDG||Early Phase 1|
The abuse of high doses of alcohol is associated with cognitive impairment that in extreme cases can result in dementia. However, the mechanisms underlying the neurotoxic effects of alcohol to the human brain are poorly understood. Here we test the hypothesis that alcohol-induced neuroinflammation contributes to its neurotoxic effects in humans
Objectives: The primary objectives are to assess if there is inflammation in the brain of alcoholics and if present to determine if it recovers after 3 weeks of abstinence as compared between groups (alcoholic vs. healthy volunteers) in Phase I. Secondary outcomes are to evaluate the functional consequences of inflammation as assessed by: regional brain glucose metabolism, functional brain activation to cognitive tasks, structural brain imaging, resting functional connectivity and neuropsychological tests.
Study population: Participants diagnosed with alcohol use disorder (AD) as per DSM IV or DSM 5 AD and healthy controls. Males and females ages 30-75 will be included
Design: This study has two phases (phase I and II). The two phases can be done as inpatient (AD subjects) or as outpatient (AD and healthy controls) over a 2-3 day period. In phase I participants will undergo two positron emission tomography (PET) scans, one with [11C]PBR28 (marker of neuroinflammation) and one with 18FDG (marker of brain glucose metabolism) and magnetic resonance imaging (MRI) scans to assess brain structure, functional reactivity and functional connectivity. In parallel we will perform neuropsychological tests (NP). Phase II will include the same procedures as Phase I but it will be done about 3 weeks later over a 2-3 day period only in the participants (alcoholics or controls) who in Phase I show evidence of inflammatory changes. In AD participants Phase II will be done after alcohol abstinence and in healthy controls it will be repeated with no intervention. We will complete studies on at least ten alcoholic users (n=10) before we can feel confident that there is no neuroinflammation. In parallel we need to collect data on at least ten (n=10) controls so we have a comparison group scanned under the same characteristics as the alcoholics to do this preliminary investigation.
Outcome parameters: Main outcome measure is to assess if there is neuroinflammation with alcoholism and if it recovers with detoxification. Secondary outcome measures are: to assess if neuroinflammation is associated with markers of brain function, which include (1) regional brain glucose metabolism; (2) MRI based voxel-based morphometry (VBM) to assess cortical atrophy; (3) blood-oxygenation level-dependent (BOLD) activation to a cognitive task, (4) brain functional connectivity, (5) myo-inositol (mI) concentration, and (6) NP testing to assess cognitive performance, and to evaluate if neuroinflammation predicts relapse in AD over a 3 month follow-up period.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||144 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||None (Open Label)|
|Primary Purpose:||Basic Science|
|Official Title:||Brain Inflammation and Function in Alcoholism|
|Study Start Date :||September 6, 2014|
|Estimated Primary Completion Date :||December 31, 2021|
|Estimated Study Completion Date :||December 29, 2023|
- To assess if there is inflammation in the brain of alcoholics as measured with [11C]PBR28 and to determine if it recovers with 3 weeks of detoxification. [ Time Frame: 2020 ]
- To assess the impact of neuroinflammation on brain function (assessed with PET and 18FDG and with MRI for fMRI with task activation and for functional connectivity). [ Time Frame: 2020 ]
- To determine if the NP variables correlate with neuroinflammation. [ Time Frame: 2020 ]
- To determine if the measure of neuroinflammation predicts relapse in AD participants in the 3 month follow-up period. [ Time Frame: 2020 ]
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02233868
|Contact: Gene-Jack Wang, M.D.||(301) email@example.com|
|United States, Maryland|
|National Institutes of Health Clinical Center, 9000 Rockville Pike||Recruiting|
|Bethesda, Maryland, United States, 20892|
|Contact: For more information at the NIH Clinical Center contact Patient Recruitment and Public Liaison Office (PRPL) 800-411-1222 ext TTY8664111010 firstname.lastname@example.org|
|Principal Investigator:||Gene-Jack Wang, M.D.||National Institute on Alcohol Abuse and Alcoholism (NIAAA)|