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.
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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
OTHER
Masking
TRIPLE
Enrollment
40
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).
Yale University School of Medicine (Connecticut Mental Health Center)
New Haven, Connecticut, United States
Number of drinks consumed
Total number of drinks (out of 12) that were consumed during each of the two alcohol drinking paradigm (ADP) session.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: ADP Lab Session 1 (Day 1) and ADP Lab Session 2 (3-5 days later)
Change in Systolic Blood Pressure
Mean change in systolic blood pressure in mmHg
Time frame: Medication dosing/ADP Lab Session 1 (Day 1) and medication dosing/ADP Lab Session 2 (3-5 days later)
Change in Diastolic Blood Pressure
Mean change in diastolic blood pressure in mmHg
Time frame: Medication dosing/ADP Lab Session 1 (Day 1) and medication dosing/ADP Lab Session 2 (3-5 days later)
Change in Heart Rate
Mean change in heart rate measured in beats per minute
Time frame: Medication dosing/ADP Lab Session 1 (Day 1) and medication dosing/ADP Lab Session 2 (3-5 days later)
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.