Pilot Study: Effects of Nimodipine on Alcohol Drinking

NCT06900998 | Not Yet Recruiting Phase 2 DMC FDA Drug

• 2 other identifiers: 20000385662P50AA012870-21
• Study Type: interventional
• Target: 5
• Locations: 1 country
• Sites: 1

Brief Summary

This is an open label trial aiming to recruit 5 non-treatment seeking adults with Alcohol Use Disorder. All will participate in an alcohol drinking paradigm (ADP) lab session at the Hospital Research Unit (HRU) at Yale-New Haven Hospital (YNHH). Participants will stay overnight and receive nimodipine 90 mg/dose every six hours during an 18-hour period prior to the ADP to allow for the limited central nervous system bioavailability of this drug. Electroencephalogram (EEG) data will be collected before the first dose and after the last dose of nimodipine. Adverse events will be closely monitored during this period. During the ADP session participants will receive a priming dose of alcohol followed by a one-hour monitoring period. This will be followed by three one-hour self-administration periods; during each hour, participants will be able to choose between drinking up to four drinks or receive the monetary equivalents of these drinks (total of 12 drinks over three hours).

Conditions

Alcohol Use Disorder

Outcome Measures

Primary Outcomes (4)

• Number of drinks consumed

  Total number of drinks (out of 12) that were consumed during the alcohol drinking paradigm (ADP) session.

  Lab Session 1 (Day 1)

• Alcohol Craving using Yale Craving Scale

  Craving for alcohol based on Yale Craving Scale, scores ranging from 0-112 mm on a visual analog scale, with higher measurements indicating higher craving.

  Lab Session 1 (Day 1)

• Stimulation Effect

  Stimulation effect collected using the Biphasic Alcohol Effect Scale. Brief Biphasic Alcohol Effects Scale-Stimulation subscale, measuring stimulation effects of alcohol on an 11-point rating scale from 0=Not at All to 10=Extremely, total scores ranging from 0 - 30, with higher measurements indicating higher stimulation.

  Lab Session 1 (Day 1)

• Sedation Effect

  Stimulation effect collected using the Biphasic Alcohol Effect Scale. Brief Biphasic Alcohol Effects Scale-Sedation subscale, measuring sedation effects of alcohol on Day 7, 6 items, 11-point rating scale from 0=Not at All to 10=Extremely, total scores ranging from 0 - 30, with higher measurements indicating higher sedation.

  Lab Session 1 (Day 1)

Secondary Outcomes (3)

• Change in Systolic Blood Pressure

  Lab Session 1 (Days 0 and 1)

• Change in Diastolic Blood Pressure

  Lab Session 1 (Days 0 and 1)

• Change in Heart Rate

  Lab Session 1 (Days 0 and 1)

Study Arms (1)

Nimodipine

EXPERIMENTAL

All participants will be assigned to this arm and will receive study drug (nimodipine), open label.

Drug: Nimodipine

Interventions

Nimodipine DRUG

Nimodipine will be administered orally beginning on the evening prior to the study lab session. 90mg doses will be administered at 6:00pm, 12:00am, 6:00am, and 12:00pm.

Nimodipine

Eligibility Criteria

• Age: 21 Years - 50 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Ages 21-50 (The lower limit is to avoid offering alcohol to individuals below the drinking age of 21. The upper age is determined by experience recruiting for our prior studies).
• Ability to read English at 6th grade level or higher.
• Meet DSM-V criteria for at least moderate AUD.
• Average weekly alcohol consumption of 30-70 standard drinks for men and 20-65 drinks for women. The lower limits are consistent with the lower sex-specific cut-offs defining high-risk drinking based on World Health Organization Risk Levels (WHO, 2000); the upper limits are designed to avoid recruiting participants whose drinking is likely to exceed the number of drinks available in the alcohol drinking paradigm (ADP).

You may not qualify if:

• Individuals who are seeking alcohol treatment or have been in alcohol treatment within the past 6 months.
• Meet current DSM-V criteria for substance use disorder, except for tobacco use disorder or mild cannabis use disorder.
• Positive urine drug screens at more than 1 baseline appointment for opiates, cocaine, benzodiazepines, and barbiturates.
• Psychotic or other severe psychiatric disorders as determined by clinical evaluation.
• Regular use of psychoactive drugs, except for individuals on a stable dose of an antidepressant for at least 2 months.
• Heart rate of less than 50 bpm.
• Clinically significant abnormalities in screening laboratories, including aspartate aminotransferase (AST) \>3 times upper limit of normal (ULN); alanine aminotransferase (ALT) \> 3 times ULN; total bilirubin \>1.5 times ULN; serum creatinine \>2.0 times ULN.
• Concurrent use of the following medications: CYP3A4 inhibitors and inducers, other calcium channel blockers, or other blood pressure lowering medications.
• Neurological trauma or disease, delirium, or hallucinations, or clinically significant or unstable medical conditions, including uncontrolled hypertension or diabetes, or significant cardiac, pulmonary, renal, hepatic, endocrine, or other systemic diseases, which in the opinion of the study physician and PI, may put the patient at risk because of participation in the study.
• Clinical Institute Withdrawal Assessment for Alcohol-Revised (CIWA-Ar) scores of 8 or greater or a history of significant repeated alcohol withdrawals to reduce the likelihood of withdrawal symptomatology if subjects reduce their drinking.
• Women who are pregnant or nursing.
• Participants who refuse to use a reliable method of birth control from the time of first medication administration to 7 days after. These include oral contraceptives, contraceptive sponge, patch, double barrier (diaphragm/spermicidal or condom/spermicidal), intrauterine contraceptive system, etonogestrel implant, medroxyprogesterone acetate contraceptive injection, complete abstinence from sexual intercourse, hormonal vaginal contraceptive ring, surgical sterilization, or true abstinence.
• Subjects who report disliking spirits will be excluded because hard liquor will be provided during the ADP.
• Subjects who have taken any investigational drug within 4 weeks of the anticipated date of the first study dose.
• Individuals who report heavy drinking days in the 2 days prior to their intake appointment but have a negative ethyl glucuronide (EtG) test to rule out subjects who are misrepresenting their drinking history.

Sponsors & Collaborators

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

Study Sites (1)

Yale University School of Medicine (Connecticut Mental Health Center)

New Haven, Connecticut, 06519, United States

Location

Related Publications (1)

• Krupitsky EM, Burakov AM, Romanova TN, Grinenko NI, Grinenko AY, Fletcher J, Petrakis IL, Krystal JH. Attenuation of ketamine effects by nimodipine pretreatment in recovering ethanol dependent men: psychopharmacologic implications of the interaction of NMDA and L-type calcium channel antagonists. Neuropsychopharmacology. 2001 Dec;25(6):936-47. doi: 10.1016/S0893-133X(01)00346-3.

  PMID: 11750186 BACKGROUND

MeSH Terms

Conditions

Alcoholism

Interventions

Nimodipine

Condition Hierarchy (Ancestors)

Alcohol-Related Disorders; Substance-Related Disorders; Chemically-Induced Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Dihydropyridines; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nicotinic Acids

Study Officials

• Suchitra Krishnan-Sarin

  Yale University School of Medicine, Dept of Psychiatry

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Thomas Liss

CONTACT

2034447545; thomas.liss@yale.edu

Nicholas Franco

CONTACT

2039745759; nicholas.franco@yale.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Psychiatry

Study Record Dates

• First Submitted: March 21, 2025
• First Posted: March 28, 2025
• Study Start (Estimated): September 1, 2026
• Primary Completion (Estimated): June 30, 2032
• Study Completion (Estimated): June 30, 2032
• Last Updated: March 17, 2026

Record last verified: 2025-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)