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| ID | Type | Description | Link |
|---|---|---|---|
| 2P50AA012870-21 | U.S. NIH Grant/Contract | View source |
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| Name | Class |
|---|---|
| National Institute on Alcohol Abuse and Alcoholism (NIAAA) | NIH |
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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).
This is an open label trial. Five adults, 21-50 years of age, with Alcohol Use Disorder, who are not looking for treatment for their drinking behaviors, and who consume at least 30-70 standard drinks for men or 25-65 standard drinks for women per week will be recruited. Participants will be screened for eligibility including a full physical exam. All will participate in an alcohol drinking paradigm (ADP) lab session at Yale New Haven Hospital's Hospital Research Unit (HRU). Participants will receive nimodipine 90 mg/dose every six hours during an 18-hour period prior to the ADP session while admitted to the HRU overnight. Additionally, electroencephalography (EEG) data will be collected while at the HRU. 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, the administration schedule used will be similar to that used in the Krupitsky trial. In that study 26 alcohol-dependent patients (who had not consumed alcohol for a month) received treatment with 90 mg dose of nimodipine every 6 hours (4 doses over 18 hours) 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 did not report any adverse events following exposure to this dose, blood pressure and adverse events will be closely monitored during the treatment period prior to the ADP (monitored at time of each dosing and again 30 minutes, 1 hour, and 2 hours after each dose). During the ADP session, participants will receive a priming dose of alcohol at 1:00pm 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 four drinks or monetary equivalents of these drinks (total of 12 drinks over three hours).
After the ADP, participants will be given dinner, and breath alcohol levels will be assessed until 10pm. If at 10pm, a participant has a breath alcohol level less than .03, they will be discharged; if greater than .03 but less than .05, a nurse on the clinical unit will evaluate to ensure the participant is alert and oriented and has no visible signs of intoxication (slurred speech, unsteady gait). If cleared by the nurse, instructions will be given to not drive or operate heavy machinery for the rest of the night. If not cleared, the nurse will continue to monitor until clearance is given. All participants will then be discharged and provided an Uber ride home.
Participants will have 2 follow-up visits 1-week and 1-month after the ADP session.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Nimodipine | Experimental | All participants will be assigned to this arm and will receive study drug (nimodipine), open label. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| 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. |
| Measure | Description | Time Frame |
|---|---|---|
| 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) |
| Measure | Description | Time Frame |
|---|---|---|
| Change in Systolic Blood Pressure | Mean change in systolic blood pressure in mmHg | Lab Session 1 (Days 0 and 1) |
| Change in Diastolic Blood Pressure | Mean change in diatolic blood pressure in mmHg |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Thomas Liss | Contact | 2034447545 | thomas.liss@yale.edu | |
| Nicholas Franco | Contact | 2039745759 | nicholas.franco@yale.edu |
| Name | Affiliation | Role |
|---|---|---|
| Suchitra Krishnan-Sarin | Yale University School of Medicine, Dept of Psychiatry | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Yale University School of Medicine (Connecticut Mental Health Center) | New Haven | Connecticut | 06519 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 11750186 | Background | 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. |
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This is a pilot study done to inform procedures for a larger clinical trial. There are no plans to share IPD at this time.
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| ID | Term |
|---|---|
| D000437 | Alcoholism |
| ID | Term |
|---|---|
| D019973 | Alcohol-Related Disorders |
| D019966 | Substance-Related Disorders |
| D064419 | Chemically-Induced Disorders |
| D001523 | Mental Disorders |
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| ID | Term |
|---|---|
| D009553 | Nimodipine |
| ID | Term |
|---|---|
| D004095 | Dihydropyridines |
| D011725 | Pyridines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
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| Lab Session 1 (Days 0 and 1) |
| Change in Heart Rate | Mean change in heart rate measured in beats per minute | Lab Session 1 (Days 0 and 1) |
| D009539 |
| Nicotinic Acids |