NCT02233868

Brief Summary

Background: \- Brain inflammation due to high alcohol intake may affect thinking, memory, and concentration. Researchers want to measure this using positron emission tomography (PET). Objective: \- To study how excessive alcohol consumption affects brain function. Eligibility:

  • Adults 30-75 years old who are moderate or severe alcohol drinkers.
  • Healthy volunteers. Design:
  • 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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
74

participants targeted

Target at P75+ for early_phase_1

Timeline
Completed

Started Feb 2015

Longer than P75 for early_phase_1

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

September 6, 2014

Completed
3 days until next milestone

First Posted

Study publicly available on registry

September 9, 2014

Completed
5 months until next milestone

Study Start

First participant enrolled

February 19, 2015

Completed
6.5 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

August 16, 2021

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

August 16, 2021

Completed
Last Updated

April 14, 2026

Status Verified

January 29, 2026

Enrollment Period

6.5 years

First QC Date

September 6, 2014

Last Update Submit

April 11, 2026

Conditions

Alcohol Use Disorder (AUD)

Keywords

Imaging StudiesAlcohol Use Disorder (AUD)Inflammation

Outcome Measures

Primary Outcomes (3)

  • To determine if there is neuroinflammation in the brain.

    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.

    end of study

  • To assess inflammation in brain.

    To assess if there is inflammation detected in the brain of alcoholics subjects as measured with \[11C\]PBR28 as compared to healthy controls.

    end of study

  • 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.

    We want to see whether \[11C\]PBR28 uptake in the brain reflects levels similar to controls after at least 3 weeks of alcohol abstinence.

    end of study

Secondary Outcomes (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).

    end of study

Study Arms (2)

Phase I

EXPERIMENTAL

PET scan with \[11C\]PBR28 followed by PET scan with FDG and MRI.

Other: connectivityDrug: neuroinflammationOther: neurofunction

Phase II

EXPERIMENTAL

After 3 weeks of abstinence or non-abstinence, PET scan with \[11C\]PBR28 followed by PET scan with FDG and MRI are repeated.

Other: connectivityDrug: neuroinflammationOther: neurofunction

Interventions

connectivityOTHER

Magnetic resonance imaging (MRI) scans will be done to assess brain structure, functional reactivity and functional connectivity.

Phase IPhase II
neuroinflammationDRUG

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.

Phase IPhase II
neurofunctionOTHER

To assess regional brain glucose metabolism.

Phase IPhase II

Eligibility Criteria

Age30 Years - 75 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • All Participants
  • Between 30 and 75 years of age.
  • 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.
  • 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
  • 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.
  • Participants seeking treatment for their AD as well as those not seeking treatment for their AD will be included.
  • Minimum 5 year history of heavy drinking (self-report).
  • Must consume at least 20 alcoholic drinks per week (male) or 15 per week (female) (self-report).
  • 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).
  • Alcohol specified as the preferred drug (self-report).

You may not qualify if:

  • All Participants
  • Major medical problems that can permanently impact brain function (e.g., CNS, cardiovascular, metabolic, autoimmune, endocrine) as determined by history and clinical exam.
  • Any clinically significant laboratory finding as determined during the screening procedures that could impact brain function or study procedures (evidenced from clinical laboratory results).
  • 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)
  • Head trauma with loss of consciousness for more than 30 minutes (self-report, medical history);
  • Positive test for alcohol on the day of the PET, the MRI or the NP tests (clinical laboratory results).
  • Urine positive for psychoactive drugs (clinical laboratory results) on study days involving imaging (PET and MRI) and neuropsychological testing.
  • Pregnant or breast feeding (self-report)
  • History of coagulation disorder (clinical laboratory results, medical history)
  • Have a history of allergic reaction to lidocaine (self-report, medical history)
  • 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).
  • Cannot lie comfortably flat on your back for up to 2 hours in the PET and MRI scanners (self-report).
  • Body weight \> 250 kg. The MR scanner bed is tested to a weight limit of 250 kg (\~550 lbs).
  • Have a positive HIV test (clinical laboratory results, medical history).
  • Homozygosity for the rs6971 polymorphism on TSPO that results in LB (Owen et al 2011) (genotyping results).
  • +2 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

Location

Related Publications (1)

  • Paul S, Gallagher E, Liow JS, Mabins S, Henry K, Zoghbi SS, Gunn RN, Kreisl WC, Richards EM, Zanotti-Fregonara P, Morse CL, Hong J, Kowalski A, Pike VW, Innis RB, Fujita M. Building a database for brain 18 kDa translocator protein imaged using [11C]PBR28 in healthy subjects. J Cereb Blood Flow Metab. 2019 Jun;39(6):1138-1147. doi: 10.1177/0271678X18771250. Epub 2018 May 11.

    PMID: 29749279DERIVED

Related Links

MeSH Terms

Conditions

AlcoholismInflammation

Condition Hierarchy (Ancestors)

Alcohol-Related DisordersSubstance-Related DisordersChemically-Induced DisordersMental DisordersPathologic ProcessesPathological Conditions, Signs and Symptoms

Study Officials

  • Dardo G Tomasi, Ph.D.

    National Institute on Alcohol Abuse and Alcoholism (NIAAA)

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
early phase 1
Allocation
NA
Masking
NONE
Purpose
BASIC SCIENCE
Intervention Model
PARALLEL
Sponsor Type
NIH
Responsible Party
SPONSOR

Study Record Dates

First Submitted

September 6, 2014

First Posted

September 9, 2014

Study Start

February 19, 2015

Primary Completion

August 16, 2021

Study Completion

August 16, 2021

Last Updated

April 14, 2026

Record last verified: 2026-01-29

Data Sharing

IPD Sharing
Will not share

Data is analyzed by subject group and not on an individual basis.

Locations

US(1)