이 페이지는 자동 번역되었으며 번역의 정확성을 보장하지 않습니다. 참조하십시오 영문판 원본 텍스트의 경우.

Effects of Nimodipine on Alcohol Drinking

2026년 6월 25일 업데이트: 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.

연구 개요

상태

아직 모집하지 않음

상세 설명

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.

연구 유형

중재적

등록 (추정된)

40

단계

  • 2 단계

연락처 및 위치

이 섹션에서는 연구를 수행하는 사람들의 연락처 정보와 이 연구가 수행되는 장소에 대한 정보를 제공합니다.

연구 연락처

연구 연락처 백업

연구 장소

    • Connecticut
      • New Haven, Connecticut, 미국, 06519
        • Yale University School of Medicine (Connecticut Mental Health Center)

참여기준

연구원은 적격성 기준이라는 특정 설명에 맞는 사람을 찾습니다. 이러한 기준의 몇 가지 예는 개인의 일반적인 건강 상태 또는 이전 치료입니다.

자격 기준

공부할 수 있는 나이

  • 성인

건강한 자원 봉사자를 받아들입니다

아니

설명

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.

공부 계획

이 섹션에서는 연구 설계 방법과 연구가 측정하는 내용을 포함하여 연구 계획에 대한 세부 정보를 제공합니다.

연구는 어떻게 설계됩니까?

디자인 세부사항

  • 주 목적: 다른
  • 할당: 무작위
  • 중재 모델: 크로스오버 할당
  • 마스킹: 삼루타

무기와 개입

참가자 그룹 / 팔
개입 / 치료
실험적: 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).
실험적: 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).

연구는 무엇을 측정합니까?

주요 결과 측정

결과 측정
측정값 설명
기간
Number of drinks consumed
기간: 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
기간: 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
기간: 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
기간: 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)

2차 결과 측정

결과 측정
측정값 설명
기간
Change in Systolic Blood Pressure
기간: 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
기간: 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
기간: 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)

기타 결과 측정

결과 측정
측정값 설명
기간
Changes in brain circuit hyperexcitation - Preprocessing and source analysis
기간: 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
기간: 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)

공동 작업자 및 조사자

여기에서 이 연구와 관련된 사람과 조직을 찾을 수 있습니다.

스폰서

수사관

  • 수석 연구원: Suchitra Krishnan-Sarin, Yale University School of Medicine, Dept of Psychiatry

간행물 및 유용한 링크

연구에 대한 정보 입력을 담당하는 사람이 자발적으로 이러한 간행물을 제공합니다. 이것은 연구와 관련된 모든 것에 관한 것일 수 있습니다.

일반 간행물

연구 기록 날짜

이 날짜는 ClinicalTrials.gov에 대한 연구 기록 및 요약 결과 제출의 진행 상황을 추적합니다. 연구 기록 및 보고된 결과는 공개 웹사이트에 게시되기 전에 특정 품질 관리 기준을 충족하는지 확인하기 위해 국립 의학 도서관(NLM)에서 검토합니다.

연구 주요 날짜

연구 시작 (추정된)

2026년 9월 1일

기본 완료 (추정된)

2032년 6월 30일

연구 완료 (추정된)

2032년 6월 30일

연구 등록 날짜

최초 제출

2026년 3월 25일

QC 기준을 충족하는 최초 제출

2026년 6월 25일

처음 게시됨 (실제)

2026년 7월 2일

연구 기록 업데이트

마지막 업데이트 게시됨 (실제)

2026년 7월 2일

QC 기준을 충족하는 마지막 업데이트 제출

2026년 6월 25일

마지막으로 확인됨

2026년 3월 1일

추가 정보

이 연구와 관련된 용어

개별 참가자 데이터(IPD) 계획

개별 참가자 데이터(IPD)를 공유할 계획입니까?

예

IPD 계획 설명

Deidentified individual data will be shared.

약물 및 장치 정보, 연구 문서

미국 FDA 규제 의약품 연구

예

미국 FDA 규제 기기 제품 연구

아니

이 정보는 변경 없이 clinicaltrials.gov 웹사이트에서 직접 가져온 것입니다. 귀하의 연구 세부 정보를 변경, 제거 또는 업데이트하도록 요청하는 경우 register@clinicaltrials.gov. 문의하십시오. 변경 사항이 clinicaltrials.gov에 구현되는 즉시 저희 웹사이트에도 자동으로 업데이트됩니다. .

구독하다