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Brain Inflammation and Function in Alcoholism

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT02233868
Recruitment Status : Recruiting
First Posted : September 9, 2014
Last Update Posted : May 8, 2019
Information provided by (Responsible Party):
National Institutes of Health Clinical Center (CC) ( National Institute on Alcohol Abuse and Alcoholism (NIAAA) )

Brief Summary:


- 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

Detailed Description:

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 144 participants
Allocation: Non-Randomized
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, 2022
Estimated Study Completion Date : December 29, 2023

Resource links provided by the National Library of Medicine

Intervention Details:
  • Device: MRI
    Functional Connectivity Magnetic Resonance Imaging (fcMRI) of connectivity in brain
  • Drug: C-11PBR28
    PET brain imaging of neuroinflammation using the radiotracer [11C]PBR28
  • Drug: F-18FDG
    PET brain imaging of neurofunction using the radiotracer F-18FDG

Primary Outcome Measures :
  1. 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 ]

Secondary Outcome Measures :
  1. 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 ]
  2. To determine if the NP variables correlate with neuroinflammation. [ Time Frame: 2020 ]
  3. To determine if the measure of neuroinflammation predicts relapse in AD participants in the 3 month follow-up period. [ Time Frame: 2020 ]

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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Ages Eligible for Study:   30 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes


-All Participants

  1. Between 30 and 75 years of age.
  2. Ability to provide written informed consent as determined by physical examination and verbal communication. Capacity to consent will be determined by those giving the informed consent.
  3. Females: Negative urine pregnancy test and not currently breastfeeding. Post-menopausal or surgically sterile (tubal ligation or hysterectomy); or not sexually active with a male partner and able to get pregnant; or documented agreement to use an effective form of birth control. Acceptable forms of contraception include: hormonal contraceptives (birth-control pills, injectable hormones, vaginal-ring hormones); IUD; diaphragm with spermicide; condom with spermicide.

    -Specific For AD Participants

  4. DSM-IV diagnosis of alcohol dependence or alcohol abuse or DSM-5 diagnosis of moderate or severe alcohol use disorder (established through history and clinical exam). We include subjects that drink high doses of alcohol since alcohol's detrimental effects are greater with larger doses and particularly with binge drinking.
  5. Participants seeking treatment for their AD as well as those not seeking treatment for their AD will be included.
  6. Minimum 5 year history of heavy drinking (self-report).
  7. Must consume at least 20 alcoholic drinks per week (male) or 15 per week (female) (self-report).
  8. Must have had the last drinking episode (females 3 or more drinks; and males 4 or more drinks) within 1 week of baseline PET scan (self-report).
  9. Alcohol specified as the preferred drug (self-report).


  • All Participants

    1. Unwilling or unable to refrain from use within 24 hours of scheduled study procedures: psychoactive medications or medication that may affect study results (e.g., analgesics [non narcotic], antibiotics (must finish course at least 24 hours prior to a scheduled procedure), antidiarrheal preparations, anti-inflammatory drugs (systemic corticosteroids are exclusionary), antinauseants, cough/cold preparations) (self-report, medical history). The following medications are allowable for entry on this study: analgesics (non-narcotic); antacids; antiasthma agents that are not systemic corticosteroids; antifungal agents for topical use; antihistamines (non-sedating); H2-Blockers/PPI (proton pump inhibitors); laxatives. The use of antihyperlipidemics and/or diuretics are permitted as long as they have been taken for at least 1 month before procedure visits and dose has been stabilized. The use of benzodiazepines such as alprazolam (( )Xanax), diazepam (( )Valium) and lorazepam (( )Ativan), will not exclude participants from this study.
    2. Current or past DSM-IV or DSM-5 diagnosis of a psychiatric disorder (other than alcohol in AD participants and nicotine/caffeine use disorders) that required hospitalization (any length), or chronic medication management (more than 4 weeks) and that could impact brain function at the time of the study as determined by history and clinical exam. The following chronically used medications are exclusionary from the study: analgesics containing narcotics; anorexics (sibuteramine); antianginal agents; antiarrhythmics; antiasthma agents that are systemic corticosteroids; antibiotics; anticholinergics; anticoagulants; anticonvulsants; antidepressants; antidiarrheal preparations; antifungal agents (systemic); antihistamines (sedating); antihypertensives; anti-inflammatory drugs (systemic); antineoplastics; antiobesity; antipsychotics; antivirals (except for treatment of HSV with agents without CNS activity, e.g. acyclovir, ganciclovir, famciclovir, valacyclovir); anxiolytics; cough/cold preparations (dextromethorphan preparations, pseudoephedrine); hormones (exceptions: thyroid hormone replacement, oral contraceptives, and estrogen replacement therapy); insulin; lithium; muscle relaxants; psychotropic drugs not otherwise specified (nos) including herbal products (no drugs with psychomotor effects or with anxiolytics, stimulant, antipsychotic, or sedative properties); sedatives/hypnotics. Note that nicotine and/or caffeine use will not exclude participants.
    3. Major medical problems that can permanently impact brain function (e.g., CNS, cardiovascular, metabolic, autoimmune, endocrine) as determined by history and clinical exam.
    4. Any clinically significant laboratory finding as determined during the screening procedures that could impact brain function or study procedures (evidenced from clinical laboratory results).
    5. Have had previous radiation exposure (from X-rays, PET scans, or other exposure) that with the exposure from this study, would exceed NIH annual research limits (self-report, medical history)
    6. Head trauma with loss of consciousness for more than 30 minutes (self-report, medical history);
    7. Positive test for alcohol on the day of the PET, the MRI or the NP tests (clinical laboratory results).
    8. Urine positive for psychoactive drugs (clinical laboratory results) on study days involving imaging (PET and MRI) and neuropsychological testing.
    9. Pregnant or breast feeding (self-report)
    10. History of coagulation disorder (clinical laboratory results, medical history)
    11. Have a history of allergic reaction to lidocaine (self-report, medical history)
    12. Presence of ferromagnetic objects in the body that are contraindicated for MRI of the head, fear of enclosed spaces, or other standard contraindication to MRI (self-report checklist).
    13. Cannot lie comfortably flat on your back for up to 2 hours in the PET and MRI scanners (self-report).
    14. Body weight > 250 kg. The MR scanner bed is tested to a weight limit of 250 kg (~550 lbs).
    15. Have a positive HIV test (clinical laboratory results, medical history).
    16. Homozygosity for the rs6971 polymorphism on TSPO that results in LB (Owen et al 2011) (genotyping results).
    17. NIH employees who meet criteria as AD subjects. Although we will include NIH employees as healthy volunteers, study investigators and their superiors, subordinates and immediate family members (adults children, spouses, parents, siblings) will be excluded.


  • Consumption of moderate to high levels of alcohol. That includes if female, currently (within past 6 months) consuming more than 2 drinks on a given episode and if male, consuming more than 3 drinks on a given episode; and/or consuming if female, more than a total of 7 drinks a week or if male, more than 10 drinks a week (self-report).

Information from the National Library of Medicine

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 identifier (NCT number): NCT02233868

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Contact: Gene-Jack Wang, M.D. (301) 496-5012

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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   
Sponsors and Collaborators
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
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Principal Investigator: Gene-Jack Wang, M.D. National Institute on Alcohol Abuse and Alcoholism (NIAAA)

Additional Information:
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Responsible Party: National Institute on Alcohol Abuse and Alcoholism (NIAAA) Identifier: NCT02233868     History of Changes
Other Study ID Numbers: 140192
First Posted: September 9, 2014    Key Record Dates
Last Update Posted: May 8, 2019
Last Verified: October 12, 2018

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by National Institutes of Health Clinical Center (CC) ( National Institute on Alcohol Abuse and Alcoholism (NIAAA) ):
Imaging Studies

Additional relevant MeSH terms:
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Pathologic Processes
Alcohol-Related Disorders
Substance-Related Disorders
Chemically-Induced Disorders
Mental Disorders
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases