NIH Clinical Center Search the Studies: Study Number, Study Title

Protocol Details

Brain Inflammation and Function in Alcoholism

This study is currently recruiting participants.

Summary | Eligibility | Citations | Contacts

Summary

Number

14-AA-0192

Sponsoring Institute

National Institute on Alcohol Abuse and Alcoholism (NIAAA)

Recruitment Detail

Type: Participants currently recruited/enrolled
Gender: Male & Female
Min Age: 30
Max Age: 75

Referral Letter Required

No

Population Exclusion(s)

Children

Special Instructions

Currently Not Provided

Keywords

Imaging Studies;
Alcoholism;
Inflammation

Recruitment Keyword(s)

None

Condition(s)

Alcoholism

Investigational Drug(s)

[11C]PBR28

Investigational Device(s)

None

Intervention(s)

Device: MRI
Drug: C-11PBR28
Drug: F-18FDG

Supporting Site

National Institute on Alcohol Abuse and Alcoholism

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.

--Back to Top--

Eligibility

INCLUSION CRITERIA:

-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).

EXCLUSION CRITERIA:

-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.

EXCLUSION CRITERIA SPECIFIC FOR CONTROL PARTICIPANTS:

-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).


--Back to Top--

Citations:

Ward RJ, Lallemand F, de Witte P. Biochemical and neurotransmitter changes implicated in alcohol-induced brain damage in chronic or 'binge drinking' alcohol abuse. Alcohol Alcohol. 2009 Mar-Apr;44(2):128-35. doi: 10.1093/alcalc/agn100. Epub 2009 Jan 20.

Lehnardt S. Innate immunity and neuroinflammation in the CNS: the role of microglia in Toll-like receptor-mediated neuronal injury. Glia. 2010 Feb;58(3):253-63. doi: 10.1002/glia.20928.

Kreutzberg GW. Microglia: a sensor for pathological events in the CNS. Trends Neurosci. 1996 Aug;19(8):312-8.

--Back to Top--

Contacts:

Principal Investigator

Referral Contact

For more information:

Gene-Jack Wang, M.D.
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
BG 10 RM B2L124
10 CENTER DR
BETHESDA MD 20814
(301) 496-5012
gene-jack.wang@nih.gov

Gene-Jack Wang, M.D.
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
BG 10 RM B2L124
10 CENTER DR
BETHESDA MD 20814
(301) 496-5012
gene-jack.wang@nih.gov

Office of Patient Recruitment
National Institutes of Health Clinical Center (CC)
Building 61, 10 Cloister Court
Bethesda, Maryland 20892
Toll Free: 1-800-411-1222
Local Phone: 301-451-4383
TTY: 1-866-411-1010
PRPL@cc.nih.gov

Clinical Trials Number:

NCT02233868

--Back to Top--