Nimodipine for Alcoholism

Overseen By Nicholas Franco

Age: 18 - 65

Sex: Any

Trial Phase: Phase 2

Sponsor: Yale University

Must not be taking: CYP3A4 inhibitors, Calcium channel blockers

Disqualifiers: Substance use disorder, Hypertension, Diabetes, Pregnancy, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 4

Duration: 1 day

5 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial requires that you stop taking certain medications, specifically CYP3A4 inhibitors and inducers, other calcium channel blockers, or other blood pressure lowering medications. If you are on a stable dose of an antidepressant for at least 2 months, you may continue taking it.

What evidence supports the effectiveness of the drug nimodipine for treating alcoholism?

Some studies suggest that nimodipine may help reduce anxiety and depression in people with alcoholism, and it might also decrease the urge to drink during recovery. Additionally, nimodipine has shown potential in improving brain and blood vessel health in cases of chronic alcohol use. ^{1 2 3 4 5}

Is nimodipine generally safe for humans?

Nimodipine has been studied in humans for alcohol withdrawal and was generally well tolerated, with no side effects reported in one study. However, another study noted that some patients developed confusion and seizures, indicating that while it may be safe for some, it could have serious side effects for others. ^{1 2 6 7 8}

How does the drug nimodipine differ from other treatments for alcoholism?

Nimodipine is unique in its use as a calcium channel blocker, which may help reduce the reinforcing effects of alcohol and decrease anxiety and depression associated with alcohol dependence. Unlike some other treatments, it does not cause dependence or have a sedative effect, making it potentially useful for managing alcohol cravings and mood disorders during remission. ^{1 2 4 9 10}

What is the purpose of this trial?

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).

Research Team

Suchitra Krishnan-Sarin

Principal Investigator

Yale University School of Medicine, Dept of Psychiatry

Eligibility Criteria

This trial is for non-treatment seeking adults aged 21-50 with Alcohol Use Disorder who can read English at a 6th grade level or higher. Participants must drink an average of 30-70 drinks per week for men and 20-65 for women, but not be currently seeking alcohol treatment or have been in treatment within the last six months.

Inclusion Criteria

Ability to read English at 6th grade level or higher

Meet DSM-V criteria for at least moderate AUD

I am between 21 and 50 years old.

Exclusion Criteria

Positive urine drug screens at more than 1 baseline appointment for opiates, cocaine, benzodiazepines, and barbiturates

I do not like drinking spirits.

Subjects who have donated blood within the past 6 weeks

Timeline

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

1 visit (in-person)

Treatment

Participants receive nimodipine 90 mg/dose every six hours during an 18-hour period prior to the ADP session, with EEG data collection and monitoring for adverse events.

1 day

Overnight stay (in-person)

Alcohol Drinking Paradigm (ADP) Session

Participants receive a priming dose of alcohol followed by a one-hour monitoring period, then three one-hour self-administration periods where they can choose between drinks or monetary equivalents.

1 day

1 session (in-person)

Follow-up

Participants are monitored for safety and effectiveness after the ADP session with follow-up visits.

1 month

2 visits (in-person)

Treatment Details

Interventions

• Nimodipine

Trial Overview The study tests Nimodipine's effects on alcohol consumption by having participants stay overnight at Yale-New Haven Hospital, take doses of Nimodipine every six hours before an alcohol drinking session, and choose between drinking alcohol or receiving money during self-administration periods.

Participant Groups

Group I: Nimodipine Experimental Treatment 1 Intervention

All participants will be assigned to this arm and will receive study drug (nimodipine), open label.

Who Is Running the Clinical Trial?

Yale University

Lead Sponsor

Trials

1,963

Recruited

3,046,000+

National Institute on Alcohol Abuse and Alcoholism (NIAAA)

Collaborator

Trials

865

Recruited

1,091,000+

References

1. England pubmed.ncbi.nlm.nih.gov

Nimodipine in acute alcohol withdrawal state. [2019]

2. United States pubmed.ncbi.nlm.nih.gov

Nimodipine and flunarizine in alcohol withdrawal: an open study. [2012]

3. Greece pubmed.ncbi.nlm.nih.gov

Protective effects of nimodipine on cerebrovascular function in chronic alcoholic encephalopathy. [2013]

4. Russia (Federation) pubmed.ncbi.nlm.nih.gov

[The efficacy of calcium channel blockers in the treatment of affective disorders and pathologic drive for alcohol in patients with alcoholism in the remission period]. [2016]

5. Italy pubmed.ncbi.nlm.nih.gov

[Sequential nimodipine-reduced glutathione treatment in alcoholic abstinence syndrome. Preliminary experience]. [2013]

6. United States pubmed.ncbi.nlm.nih.gov

Effects of calcium channel inhibitors on ethanol effects and pharmacokinetics in healthy volunteers. [2019]

7. United States pubmed.ncbi.nlm.nih.gov

Effects of nimodipine and other calcium channel antagonists in alcohol-preferring AA rats. [2019]

8. Netherlands pubmed.ncbi.nlm.nih.gov

Nimodipine in human alcohol withdrawal syndrome--an open study. [2019]

9. England pubmed.ncbi.nlm.nih.gov

The calcium channel antagonist, nimodipine, decreases operant self-administration of low concentrations of ethanol. [2019]

10. Netherlands pubmed.ncbi.nlm.nih.gov

Studies on a model of long term alcohol drinking. [2019]