Role of Metal Ion Transporter ZIP8 in Alcohol-Related Behaviors

NCT06819189 | Recruiting Phase 1 FDA Drug

• 2 other identifiers: 10002228002228-AA
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

Brief Summary

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....

Conditions

Healthy Volunteer

Keywords

Alcohol

Outcome Measures

Primary Outcomes (1)

• Primary Endpoints: IV alcohol self-administration measures Peak breath alcohol concentration (BrAC), number of alcohol infusions received.

  The Peak BrAC and number of infusions are direct measures of alcohol exposure and amount consumed during the laboratory session.

  2 YEARS

Study Arms (1)

IV Ethanol

OTHER

IV Ethanol

Drug: Ethanol

Interventions

Ethanol DRUG

IV Ethanol

IV Ethanol

Eligibility Criteria

• Age: 21 Years - 60 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Male and female participants between 21-60 years of age. \[Based on: identification provided to Clinical Center Admissions office\].
• Non-smokers with no history of smoking in the past year and not a daily smoker for more than 1 month in their lifetime. \[Based on: smoking history questionnaire, Additional History Form\]
• Participants of European ancestry: the minor T allele of rs13107325, has a frequency of 0.08 in European ancestry, but is almost absent in Asian and African populations (http://www.ensembl.org). Due to the rare occurrence of the T allele and to avoid populations stratification in this small sample-sized study, only participants with self-reported White racial category (European ancestry) will be enrolled in this study.
• Ability to understand the written consent form and willing to sign it. \[Based on: consent quiz\].

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. \[Based on: SCID interview\]
• 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. \[Based on: laboratory tests and breathalyzer test\].
• 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.
• 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.
• 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 comfortable on back for up to 2 hours in the MRI scanner. Justification: To minimize risk and discomfort.

Sponsors & Collaborators

• National Institute on Alcohol Abuse and Alcoholism (NIAAA): lead

Study Sites (1)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

RECRUITING

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Interventions

Ethanol

Intervention Hierarchy (Ancestors)

Alcohols; Organic Chemicals

Study Officials

• Vijay A Ramchandani, Ph.D.

  National Institute on Alcohol Abuse and Alcoholism (NIAAA)

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Vijay A Ramchandani, Ph.D.

CONTACT

(301) 402-8527; vijayr@mail.nih.gov

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 8, 2025
• First Posted: February 11, 2025
• Study Start: June 10, 2025
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): December 31, 2027
• Last Updated: January 12, 2026

Record last verified: 2026-01-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)