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 : August 12, 2020
- 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|
|Alcohol Use Disorder (AUD)||Other: connectivity Other: neuroinflammation Drug: neurofunction||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 in Phase I 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 II. Phase II objectives are to assess between group differences in inflammation in the brain of AUD subjects who either abstain from alcohol for at least 3 weeks or relapse (continue to drink alcohol) for at least 3 weeks. 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 at least 3 weeks later over a 2-3 day period only in AUD participants who successfully completed phase I who either abstained from alcohol or relapsed/continued to drink alcohol after Phase I.
Relapsers would be eligible for Phase II if they continued to drink for at least 3 weeks
prior scheduled imaging studies. We will complete Phase II studies on up to 24 additional AUD subjects (n=12 abstainers and n=12 relapsers) to assess whether [11C]PBR28 uptake recovers after abstinence. Since there are not much differences between test/retest studies in healthy volunteers in the literature , there is no need to complete Phase II studies in controls.
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|
|Actual Study Start Date :||February 19, 2015|
|Estimated Primary Completion Date :||December 31, 2024|
|Estimated Study Completion Date :||December 31, 2024|
- Other: connectivity
Magnetic resonance imaging (MRI) scans will be done to assess brain structure, functional reactivity and functional connectivity.
- Other: neuroinflammation
The use of [11C] PBR28 will allow us to assess for the first time in vivo if there is neuroinflammation in the brain of alcoholics. It will also allow us to assess if it recovers with alcohol detoxification.
- Drug: neurofunction
To assess regional brain glucose metabolism.
- To assess inflammation in the brain [ Time Frame: end of study ]To assess if there is inflammation detected in the brain of alcoholics subjects as measured with [11C]PBR28 as compared to healthy controls.
- To determine if there is neuroinflammation in the brain. [ Time Frame: end of study ]To assess if there is neuroinflammation detected in the brain of alcoholics subjects as measured with [11C]PBR28 as compared to healthy controls and if it recovers with at least 3 weeks of abstinence.
- To assess between group differences in inflammation in the brain of AUD subjects in Phase II who either abstain from alcohol for at least 3 weeks or relapse (continue to drink alcohol) for at least 3 weeks. [ Time Frame: end of study ]We want to see whether [11C] PBR28 uptake in the brain reflects levels similar to controls after at least 3 weeks of alcohol abstinence.
- 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: end of study ]to assess if neuroinflammation is associated with markers of brain function and to evaluate if neuroinflammation predicts relapse in AUD over a 3 month follow-up period.
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 Office of Patient Recruitment (OPR) 800-411-1222 ext TTY8664111010 firstname.lastname@example.org|
|Principal Investigator:||Gene-Jack Wang, M.D.||National Institute on Alcohol Abuse and Alcoholism (NIAAA)|