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Effects of Nimodipine on Alcohol Drinking

2026年6月25日 更新者:Suchitra Krishnan-Sarin、Yale University

A Randomized Controlled Study on the Effects of Nimodipine on Alcohol Drinking Among Adults Who Are Heavy Alcohol Drinkers

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.

調査の概要

状態

まだ募集していません

詳細な説明

Participants with AUD who drink heavily, will participate in a double-blind, placebo-controlled, cross-over design. At baseline, eligible participants will complete an MRI scan at the Yale MR center and MEG/EEG at the VA MIND Center. ADP Lab sessions will be conducted in the CNRU at the Connecticut Mental Health Center.

Nimodipine is rapidly absorbed after oral administration & peak concentrations are achieved within 0.5 to 1.5 hours. However, due to high first-pass metabolism, initial elimination is rapid (equivalent to a half-life of 1-2 hours); consequently, the bioavailability of nimodipine is approximately 13% after oral administration and there is a need for frequent dosing. The terminal elimination half-life of nimodipine is approximately 8 to 9 hours. In order to ensure adequate exposure and CNS bioavailability investigators will follow the administration schedule used in the Krupitsky trial*1. In this study 26 alcohol-dependent patients (who had not consumed alcohol for a month) received treatment with 90 mg dose of nimodipine (in the schedule portrayed below) prior to ketamine administration; results suggest that this dose of nimodipine reduced ketamine-induced psychosis, negative symptoms, euphoria and sedation as well as the perceived similarity of ketamine effects to alcohol. While the Krupitsky trial*1 did not report any adverse events following exposure to this dose investigators will closely monitor blood pressure and adverse events during the treatment period prior to the ADP 1 (vitals monitored at time of each dosing and again 30 minutes, 1 hour, and 2 hours after each dose).

Participants will receive either NIM or PLA in random order, during two sessions, separated by 3-5 washout days (to allow flexibility in scheduling). NIM/PLA will be provided at a dose of 90 mg/every 6 hours, over an 18-hour period (4 doses totaling 360mg), with the last dose administered approx. 1-2 hours prior to the start of the ADP period at 12 pm. MEG/EEG will be obtained 1-2 hours after the 3rd dose of NIM/PLA. During the two ADP sessions, 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 blood alcohol levels.

Participants will have 2 follow-up visits at 1-week and 1-month after the ADP session.

研究の種類

介入

入学 (推定)

40

段階

  • フェーズ2

連絡先と場所

このセクションには、調査を実施する担当者の連絡先の詳細と、この調査が実施されている場所に関する情報が記載されています。

研究連絡先

研究連絡先のバックアップ

研究場所

    • Connecticut
      • New Haven、Connecticut、アメリカ、06519
        • Yale University School of Medicine (Connecticut Mental Health Center)

参加基準

研究者は、適格基準と呼ばれる特定の説明に適合する人を探します。これらの基準のいくつかの例は、人の一般的な健康状態または以前の治療です。

適格基準

就学可能な年齢

  • 大人

健康ボランティアの受け入れ

いいえ

説明

Inclusion Criteria:

  1. 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).
  2. Ability to read English at 6th grade level or higher.
  3. Meet DSM-V criteria for at least moderate AUD.
  4. 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).

Exclusion Criteria:

  1. Individuals who are seeking alcohol treatment or have been in alcohol treatment within the past 6 months.
  2. Meet current DSM-V criteria for substance use disorder, except for tobacco use disorder or mild cannabis use disorder.
  3. Positive urine drug screens at more than 1 baseline appointment for opiates, cocaine, benzodiazepines, and barbiturates.
  4. Psychotic or other severe psychiatric disorders as determined by clinical evaluation.
  5. Regular use of psychoactive drugs, except for individuals on a stable dose of an antidepressant for at least 2 months.
  6. Medical conditions that would contraindicate the consumption of alcohol or use of nimodipine including untreated or not adequately controlled hypertension or hypotension. Blood pressure at or below 100/65 will be exclusionary.
  7. Heart rate of less than 50 bpm.
  8. 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.
  9. Concurrent use of the following medications: CYP3A4 inhibitors and inducers, other calcium channel blockers, or other blood pressure lowering medications.
  10. 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.
  11. 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.
  12. Women who are pregnant or nursing.
  13. 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.
  14. Subjects who report disliking spirits will be excluded because hard liquor will be provided during the ADP.
  15. Subjects who have taken any investigational drug within 4 weeks of the anticipated date of the first study dose.
  16. 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.
  17. Subjects who have donated blood within the past 6 weeks.
  18. Heart rate of less than 50 bpm.
  19. Subjects with a history or presence of cirrhosis.
  20. MRI contraindications including incompatible implants, other metal in body (e.g. pacemakers, shrapnel, metal implants) or claustrophobia.

研究計画

このセクションでは、研究がどのように設計され、研究が何を測定しているかなど、研究計画の詳細を提供します。

研究はどのように設計されていますか?

デザインの詳細

  • 主な目的:他の
  • 割り当て:ランダム化
  • 介入モデル:クロスオーバー割り当て
  • マスキング:トリプル

武器と介入

参加者グループ / アーム
介入・治療
実験的:Nimodipine 1st / Placebo 2nd
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.
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.
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).
実験的:Placebo 1st / Nimodipine 2nd
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.
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.
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).

この研究は何を測定していますか?

主要な結果の測定

結果測定
メジャーの説明
時間枠
Number of drinks consumed
時間枠:ADP Lab Session 1 (Day 1) and ADP Lab Session 2 (3-5 days later)
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
時間枠:ADP Lab Session 1 (Day 1) and ADP Lab Session 2 (3-5 days later)
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
時間枠:ADP Lab Session 1 (Day 1) and ADP Lab Session 2 (3-5 days later)
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
時間枠:ADP Lab Session 1 (Day 1) and ADP Lab Session 2 (3-5 days later)
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)

二次結果の測定

結果測定
メジャーの説明
時間枠
Change in Systolic Blood Pressure
時間枠:Medication dosing/ADP Lab Session 1 (Day 1) and medication dosing/ADP Lab Session 2 (3-5 days later)
Mean change in systolic blood pressure in mmHg
Medication dosing/ADP Lab Session 1 (Day 1) and medication dosing/ADP Lab Session 2 (3-5 days later)
Change in Diastolic Blood Pressure
時間枠:Medication dosing/ADP Lab Session 1 (Day 1) and medication dosing/ADP Lab Session 2 (3-5 days later)
Mean change in diastolic blood pressure in mmHg
Medication dosing/ADP Lab Session 1 (Day 1) and medication dosing/ADP Lab Session 2 (3-5 days later)
Change in Heart Rate
時間枠:Medication dosing/ADP Lab Session 1 (Day 1) and medication dosing/ADP Lab Session 2 (3-5 days later)
Mean change in heart rate measured in beats per minute
Medication dosing/ADP Lab Session 1 (Day 1) and medication dosing/ADP Lab Session 2 (3-5 days later)

その他の成果指標

結果測定
メジャーの説明
時間枠
Changes in brain circuit hyperexcitation - Preprocessing and source analysis
時間枠:Pre and Post 1st Medication dosing period (Day 1) and Pre and Post 2nd medication dosing period (3-5 days later)
Magnetoencephalography/Electroencephalography (MEG/EEG) data will be preprocessed following a standard pipeline[13] including bandpass filtering (0.1-100 Hz), notch filtering (60Hz), and removal of artifacts with independent component analysis (ICA)[14-16]. For each subject, an MRI will be segmented using the FreeSurfer software suite and imported into the MEG/EEG data analysis toolbox for Matlab Brainstorm[17]. Data will be segmented into two-second epochs, and the time series will be obtained using maximum entropy on the mean (MEM)[10,11] on individual head models. Reconstructed sources of subjects will be projected on the FSAverage atlas with FreeSurfer using a spherical representation of the cortex. The Destrieux Atlas will be used to parcellate the cortex into regions of interest (ROIs) to be used to extract the time series of each ROI (ventromedial, medial and orbitofrontal). MEG/EEG to be done before the 1st and after the 3rd dose of nimodipine at each lab session.
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
時間枠:Pre and Post 1st Medication dosing period (Day 1) and Pre and Post 2nd medication dosing period (3-5 days later)

Magnetoencephalography/Electroencephalography (MEG/EEG) will be collected before the first dose and after the third dose of nimodipine at each of the 2 lab session days.

The Python implementation of the specparam algorithm (https://github.com/fooof-tools)[2] will be used to estimate the exponent χ of the PSD power law (1⁄f^χ with χ>0 )[19,4,5]. For each subject, prefrontal cortex region of interest (ROI), and signal epoch, PSD will be calculated with Welch's method and fitted with the specparam algorithm in the 20-50Hz frequency range, as the exponent in this range has the strongest correlations with excitatory/inhibitory (E/I) ratio[2]. The resulting exponents and intercepts will be averaged across epochs, to obtain a single exponent and intercept estimate per ROI per subject.

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

協力者と研究者

ここでは、この調査に関係する人々や組織を見つけることができます。

スポンサー

捜査官

  • 主任研究者:Suchitra Krishnan-Sarin、Yale University School of Medicine, Dept of Psychiatry

出版物と役立つリンク

研究に関する情報を入力する責任者は、自発的にこれらの出版物を提供します。これらは、研究に関連するあらゆるものに関するものである可能性があります。

一般刊行物

研究記録日

これらの日付は、ClinicalTrials.gov への研究記録と要約結果の提出の進捗状況を追跡します。研究記録と報告された結果は、国立医学図書館 (NLM) によって審査され、公開 Web サイトに掲載される前に、特定の品質管理基準を満たしていることが確認されます。

主要日程の研究

研究開始 (推定)

2026年9月1日

一次修了 (推定)

2032年6月30日

研究の完了 (推定)

2032年6月30日

試験登録日

最初に提出

2026年3月25日

QC基準を満たした最初の提出物

2026年6月25日

最初の投稿 (実際)

2026年7月2日

学習記録の更新

投稿された最後の更新 (実際)

2026年7月2日

QC基準を満たした最後の更新が送信されました

2026年6月25日

最終確認日

2026年3月1日

詳しくは

本研究に関する用語

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個々の参加者データ (IPD) を共有する予定はありますか?

はい

IPD プランの説明

Deidentified individual data will be shared.

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いいえ

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