Effects of Nimodipine on Alcohol Drinking

NCT07681869 | Not Yet Recruiting Phase 2 DMC FDA Drug

• 2 other identifiers: 2000038566_a2P50AA012870-21
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

This is a randomized placebo-controlled trial (RCT). Participants will be non-treatment seeking adults, 21-50 years of age, with Alcohol Use Disorders. All will participate in two alcohol drinking paradigm (ADP) sessions separated by at least 3 days at The Clinical Neuroscience Research Unit (CNRU). Participants will stay overnight and receive nimodipine (90 mg/dose) or placebo every six hours during an 18-hour period prior to each ADP. MEG and/or EEG data will be collected before the first dose and after the third dose of nimodipine (NIM) or placebo (PLA). Adverse events will be closely monitored during this period. During the ADP 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 they will be able to choose between four drinks or monetary equivalents of these drinks (total of 12 drinks over three hours). ADP outcomes will include number of drinks consumed, alcohol craving, mood changes and alcohol effects, physiological measures (heart rate, blood pressure), as well as breath alcohol levels. Investigators anticipate having to recruit up to 40 participants to achieve 20 completers.

Conditions

Alcohol Use Disorder

Outcome Measures

Primary Outcomes (4)

• Number of drinks consumed

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

  ADP Lab Session 1 (Day 1) and ADP Lab Session 2 (3-5 days later)

• Alcohol Craving using Yale Craving Scale

  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.

  ADP Lab Session 1 (Day 1) and ADP Lab Session 2 (3-5 days later)

• 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.

  ADP Lab Session 1 (Day 1) and ADP Lab Session 2 (3-5 days later)

• 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.

  ADP Lab Session 1 (Day 1) and ADP Lab Session 2 (3-5 days later)

Secondary Outcomes (3)

• Change in Systolic Blood Pressure

  Medication dosing/ADP Lab Session 1 (Day 1) and medication dosing/ADP Lab Session 2 (3-5 days later)

• Change in Diastolic Blood Pressure

  Medication dosing/ADP Lab Session 1 (Day 1) and medication dosing/ADP Lab Session 2 (3-5 days later)

• Change in Heart Rate

  Medication dosing/ADP Lab Session 1 (Day 1) and medication dosing/ADP Lab Session 2 (3-5 days later)

Other Outcomes (2)

• Changes in brain circuit hyperexcitation - Preprocessing and source analysis

  Pre and Post 1st Medication dosing period (Day 1) and Pre and Post 2nd medication dosing period (3-5 days later)

• Changes in brain circuit hyperexcitation - Power Spectral Density (PSD) Exponent Estimation

  Pre and Post 1st Medication dosing period (Day 1) and Pre and Post 2nd medication dosing period (3-5 days later)

Study Arms (2)

Nimodipine 1st / Placebo 2nd

EXPERIMENTAL

Participants randomized to the Nimodipine 1st Arm will be administered Nimodipine prior to their 1st ADP session. Then after a washout period, participants will take a matching placebo prior to the 2nd lab session.

Drug: Nimodipine; Drug: Placebo

Placebo 1st / Nimodipine 2nd

EXPERIMENTAL

Participants randomized to the Placebo1st Arm will be administered matching placebo prior to their 1st ADP session. Then after a washout period, participants will be administered Nimodipine prior to the 2nd lab session.

Drug: Nimodipine; Drug: Placebo

Interventions

Nimodipine DRUG

Nimodipine 90mg/dose or matching placebo will be administered every 6 hours for the duration of 18 hours (approx 6pm, 12am, 6am, 12pm). In total, participants will receive a total of 4 doses totaling to 360mg.

Nimodipine 1st / Placebo 2nd; Placebo 1st / Nimodipine 2nd

Placebo DRUG

Matching placebo will be administered on the same schedule as Nimodipine, every 6 hours for the duration of 18 hours (approx 6pm, 12am, 6am, 12pm).

Nimodipine 1st / Placebo 2nd; Placebo 1st / Nimodipine 2nd

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 (11)

• 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

• Donoghue T, Haller M, Peterson EJ, Varma P, Sebastian P, Gao R, Noto T, Lara AH, Wallis JD, Knight RT, Shestyuk A, Voytek B. Parameterizing neural power spectra into periodic and aperiodic components. Nat Neurosci. 2020 Dec;23(12):1655-1665. doi: 10.1038/s41593-020-00744-x. Epub 2020 Nov 23.

  PMID: 33230329 BACKGROUND

• Freeman WJ, Holmes MD, Burke BC, Vanhatalo S. Spatial spectra of scalp EEG and EMG from awake humans. Clin Neurophysiol. 2003 Jun;114(6):1053-68. doi: 10.1016/s1388-2457(03)00045-2.

  PMID: 12804674 BACKGROUND

• Freeman WJ, Rogers LJ, Holmes MD, Silbergeld DL. Spatial spectral analysis of human electrocorticograms including the alpha and gamma bands. J Neurosci Methods. 2000 Feb 15;95(2):111-21. doi: 10.1016/s0165-0270(99)00160-0.

  PMID: 10752481 BACKGROUND

• Chowdhury RA, Zerouali Y, Hedrich T, Heers M, Kobayashi E, Lina JM, Grova C. MEG-EEG Information Fusion and Electromagnetic Source Imaging: From Theory to Clinical Application in Epilepsy. Brain Topogr. 2015 Nov;28(6):785-812. doi: 10.1007/s10548-015-0437-3. Epub 2015 May 28.

  PMID: 26016950 BACKGROUND

• Chowdhury RA, Pellegrino G, Aydin U, Lina JM, Dubeau F, Kobayashi E, Grova C. Reproducibility of EEG-MEG fusion source analysis of interictal spikes: Relevance in presurgical evaluation of epilepsy. Hum Brain Mapp. 2018 Feb;39(2):880-901. doi: 10.1002/hbm.23889. Epub 2017 Nov 21.

  PMID: 29164737 BACKGROUND

• Cortes-Briones J, Skosnik PD, Mathalon D, Cahill J, Pittman B, Williams A, Sewell RA, Ranganathan M, Roach B, Ford J, D'Souza DC. Delta9-THC Disrupts Gamma (gamma)-Band Neural Oscillations in Humans. Neuropsychopharmacology. 2015 Aug;40(9):2124-34. doi: 10.1038/npp.2015.53. Epub 2015 Apr 24.

  PMID: 25709097 BACKGROUND

• De Clercq W, Vergult A, Vanrumste B, Van Paesschen W, Van Huffel S. Canonical correlation analysis applied to remove muscle artifacts from the electroencephalogram. IEEE Trans Biomed Eng. 2006 Dec;53(12 Pt 1):2583-7. doi: 10.1109/TBME.2006.879459.

  PMID: 17153216 BACKGROUND

• De Vos M, Ries S, Vanderperren K, Vanrumste B, Alario FX, Van Huffel S, Burle B. Removal of muscle artifacts from EEG recordings of spoken language production. Neuroinformatics. 2010 Jun;8(2):135-50. doi: 10.1007/s12021-010-9071-0.

  PMID: 20480401 BACKGROUND

• Tadel F, Baillet S, Mosher JC, Pantazis D, Leahy RM. Brainstorm: a user-friendly application for MEG/EEG analysis. Comput Intell Neurosci. 2011;2011:879716. doi: 10.1155/2011/879716. Epub 2011 Apr 13.

  PMID: 21584256 BACKGROUND

• Gao R, Penzes P. Common mechanisms of excitatory and inhibitory imbalance in schizophrenia and autism spectrum disorders. Curr Mol Med. 2015;15(2):146-67. doi: 10.2174/1566524015666150303003028.

  PMID: 25732149 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: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Masking Details: Double blind, only statistician and pharmacist will not be masked.
• Purpose: OTHER
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Yale University School of Medicine, Dept of Psychiatry

Model Details: Participants will receive NIM or PLA in random order, during two sessions, separated by a washout period.

Study Record Dates

• First Submitted: March 25, 2026
• First Posted: July 2, 2026
• Study Start (Estimated): September 1, 2026
• Primary Completion (Estimated): June 30, 2032
• Study Completion (Estimated): June 30, 2032
• Last Updated: July 2, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will share

Locations

US (1)