Role of Metal Ion Transporter ZIP8 in Alcohol-Related Behaviors

Recruiting now · Phase 1

Conditions studied: Healthy Volunteer

In brief

Background: Alcohol use disorder (AUD) can damage people s health, work, and family. Researchers want to know more about why some people are more vulnerable to AUD than others. The ZIP8 gene may be linked to an increased risk of AUD. Researchers want to find out how different forms of the ZIP8 gene affect how healthy people drink alcohol and how alcohol affects their brain. Objective: To study how genes may affect how people drink alcohol and how it affects their brain. Eligibility: Healthy people aged 21 to 60 years. They must not smoke, and they must have no history of AUD. They must have European ancestry and be enrolled in Natural History Protocol (14-AA-0181). Design: Participants will have 2 study visits. At the first visit, participants will be given alcohol; it will be infused through a tube attached to a needle inserted into a vein. They may self-administer each dose by pressing a button. Over time, they will have to press the button an increasing number of times to receive more alcohol. The infusion period will last 2.5 hours. Participants will have blood samples taken and breath measurments, and they will do computer tasks and complete questionnaires during and after the infusion. After the infusion, they will remain in the clinic until their breath alcohol levels drop to a safe level. At the second visit, participants will have an imaging scan of their brain. They will do tasks and play games on a computer screen during the scan. Some participants may have an extra visit for screening. A mid-study visit may also be needed if more than 6 months pass between the 2 study visits....

Key facts

Study ID

NCT06819189

Run by

National Institute on Alcohol Abuse and Alcoholism (NIAAA)

People needed

50

Starts

2025-06-10

Expected to finish

2027-12-31

Last updated by the study team

2026-08-04

Who can join

Age: 21 and older, up to 60. Sex: any. Healthy volunteers: accepted.

You may not qualify if…

• Current history (past 12 months) of major medical illness, including CNS, cardiovascular, respiratory, gastrointestinal, hepatic, renal, endocrine, or reproductive disorders, or positive hepatitis (A, B antigen, or C), or HIV test. Justification: Many illnesses may alter the neuropsychological effects of alcohol as well as MRI measures. Hepatitis can alter liver function and alcohol pharmacokinetics. HIV infection can alter brain function. [Based on: clinically significant findings on medical history and physical exam, ECG, laboratory tests].
• Current history of psychiatric disorders, including depressive disorder, bipolar disorder, or anxiety disorders. Justification: Concurrent psychopathology can alter brain function and alcohol response. [Based on: SCID interview]
• Lifetime history of psychotic disorders, obsessive compulsive disorder (OCD), posttraumatic stress disorder (PTSD), or eating disorder. Justification: These disorders can have long-term effects on brain function and alcohol response. [Based on: SCID interview]
• Current or lifetime diagnosis of alcohol or substance use disorder. Past mild AUD or past mild SUD with no current symptoms for at least 2 years will not be exclusionary. Justification: History of moderate to severe alcohol or substance use disorder will impact brain function and alcohol response We do not anticipate past mild AUD or SUD in remission for 2+ years would have such impact on brain function and alcohol response. We will examine this in an exploratory analysis. We will also do a follow-up telephone/telehealth visit with these participants to assess any changes in alcohol or substance use or problems related to their participation in the study. [Based on: SCID interview].
• Currently seeking treatment for alcohol use disorders. Justification: It would be unethical to administer alcohol to individuals seeking treatment for alcohol problems. Also, this study does not provide treatment for individuals with alcohol use disorder. [Based on: medical history]
• Non-drinkers (alcohol-naive individuals or current abstainers) or individuals with no experience drinking 5 or more drinks on one occasion in their lifetime. Justification: It would be unethical to administer alcohol to individuals that do not drink alcohol. [Based on: medical history].
• Current or prior history of alcohol-induced flushing reactions, including rapid reddening of the face, rapid heart rate and breathing, and nausea after 1 or 2 drinks. Justification: It would not be safe to administer alcohol to individuals with the highly aversive flushing response to alcohol. [Based on: alcohol flushing questionnaire].
• Positive result on urine drug screen or positive breathalyzer during screening visit. Positive urine drug screen or breathalyzer reading during more than 1 study visit will result in participant withdrawal from the study. Justification: Current or recent exposure to alcohol or drugs of abuse could impact brain function and alcohol response. [Based on: laboratory tests and breathalyzer test].
• History of significant withdrawal symptoms or presence of clinically significant withdrawal symptoms (Clinical Institute Withdrawal Assessment (CIWA) score > 8) at screening. Justification: Withdrawal symptoms would be indicative of alcohol use disorder, which is already an exclusion criterion. Additionally, withdrawal symptoms would be a major safety concern for participants, and a major confound in the assessment of alcohol response and brain function. [Based on: CIWA assessment].
• Medication exclusion criteria: [Based on Medical history and physical exam, Additional History Form].
• Use of prescription or OTC medication known to interact with alcohol 2 weeks prior to screening or screening update visit. These include but may not be limited to: isosorbide; nitroglycerine; benzodiazepines; warfarin; anti-depressants such as amitriptyline, clomipramine and nefazodone; anti-diabetes medications such as glyburide, metformin and tolbutamide; H2-antagonists for heartburn such as famotidine, cimetidine and ranitidine; muscle relaxants; anti-epileptics including phenytoin and phenobarbital; codeine and opioid analgesics including Darvocet, Percocet and hydrocodone.
• Regular (more than once a week) or prescribed use of antihistamines, pain medicines, and anti-inflammatories such as aspirin, ibuprofen, acetaminophen, celecoxib, and naproxen, and unable to refrain from these medications for 48 hours prior to study visits.NOTE: Seasonal use of antihistamines is not-exclusionary unless participants are unable to refrain from these medications for
• 48 hours prior to study visits.
• Use of medications known to inhibit or induce enzymes that metabolize alcohol for 4 weeks prior to screening or screening update visit. These include chlorzoxazone, isoniazid, metronidazole, and disulfiram.
• Use of drugs known to affect hemodynamic response 2 weeks prior to screening or screening update visit. These include antihypertensives, insulin, and thyroid medications.
• Exclusion criteria for MRI:
• Left-handedness (Edinburgh Handedness Scale). Justification: To avoid lateralized effects on brain function measures and reduce potential variance in MRI signals.
• Presence of ferromagnetic objects in the body that are contraindicated for MRI of the head (including but not limited to pacemakers or other implanted electrical devices, brain stimulators, some types of dental implants, aneurysm clips, metallic prostheses, permanent eyeliner, implanted delivery pump, or shrapnel fragments).
• Fear of enclosed spaces. Justification: To minimize risk and discomfort.
• Inability to lie comfortably on back for up to 2 hours in the MRI scanner. Justification: To minimize risk and discomfort.
• [Based on: MRI Safety Screening Questionnaire, Additional History Form]
• Exclusion criteria for persons of childbearing potential:
• Justification: To minimize the risk of administering alcohol to pregnant or nursing persons, given the known effects of alcohol exposure on fetuses and infants.
• Pregnant [Based on: urine beta-hCG test at screening]. Persons of childbearing potential must also test negative on urine beta-hCG test at the start of every study visit.
• Breast-feeding [Based on: Medical history and physical exam].

Where it is running

• National Institutes of Health Clinical Center — Bethesda, Maryland, United States (enrolling)

Full record on ClinicalTrials.gov

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