Zonisamide for Alcoholism

Overseen By Sterling McPherson, PhD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Washington State University

Must not be taking: Alcohol medications

Disqualifiers: Severe substance use, Seizure disorder, others

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

Compensation: Varies

Number of Visits: 19

Duration: 12 weeks

205 Participants Needed

Trial Summary

What is the purpose of this trial?

A phase II randomized, double-blind, placebo-controlled clinical trial (RCT) to evaluate the ability of zonisamide (ZON) to decrease alcohol use among treatment-seeking adults with an alcohol use disorder (AUD).

Will I have to stop taking my current medications?

The trial requires that you are not currently receiving any medication for alcohol use or have taken such medication in the past 30 days. Other medications are not specifically mentioned, so it's best to discuss your current medications with the trial team.

What data supports the effectiveness of the drug Zonisamide for treating alcoholism?

Research shows that Zonisamide, an anticonvulsant drug, has been effective in reducing alcohol intake in both animal studies and human trials, indicating its potential to help treat alcohol dependence. ^{1 2 3 4 5}

Is zonisamide safe for humans?

Zonisamide has been used in over 2 million patient-years for epilepsy and is generally well-tolerated, with most side effects being mild to moderate. In studies for alcohol dependence, it was evaluated for safety and tolerability, and serious side effects were rare, similar to placebo. ^{1 3 4 6 7}

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

Zonisamide is unique because it is an anticonvulsant drug that affects multiple brain systems, including GABAergic, glutamatergic, and monoaminergic pathways, which may help reduce alcohol intake. Unlike traditional treatments for alcoholism, zonisamide is primarily used for epilepsy and has shown potential in reducing alcohol consumption in both animal studies and early human trials. ^{1 3 4 7 8}

Eligibility Criteria

The ZARRA Study is for adults aged 18-65 with an alcohol use disorder who drink heavily and are seeking treatment. They must be able to read and speak English, consent to the study, have a negative breath alcohol test, provide positive urine tests for alcohol use, and if female and of childbearing age, not be lactating and using birth control. People with severe allergies or recent detox history, other severe substance disorders (except nicotine), significant health issues or taking certain medications can't join.

Inclusion Criteria

Ability to read and speak English

Breath alcohol of 0.00 during informed consent

Seeking AUD treatment

Exclusion Criteria

Systemic autoimmune disease

I do not have any serious health issues that could make the study risky for me.

Significant risk of dangerous alcohol withdrawal, defined as a history of alcohol detoxification or seizure in the last 12 months and expression of concern by the participant about dangerous withdrawal

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive zonisamide or placebo plus standard treatment for alcohol use disorder

12 weeks

1 visit weekly (in-person or virtual)

Follow-up

Participants are monitored for safety and effectiveness after treatment

1 year

Visits at weeks 18, 38, and 54 (in-person or virtual)

Treatment Details

Interventions

• Placebo
• Zonisamide

Trial Overview This phase II trial is testing whether zonisamide (ZON) helps reduce alcohol consumption in people wanting to treat their heavy drinking habits. Participants will randomly receive either ZON or a placebo without knowing which one they're getting. The goal is to see if there's a difference in how much they drink while on these treatments.

Participant Groups

Group I: ZON+ST Experimental Treatment 1 Intervention

Zonisamide (ZON) plus standard treatment (ST)

Group II: PLO+ST Placebo Group 1 Intervention

Placebo (PLO) plus standard treatment (ST)

Who Is Running the Clinical Trial?

Washington State University

Lead Sponsor

Trials

114

Recruited

58,800+

Findings from Research

Zonisamide, when administered repeatedly, appears to reduce the sensitivity of the hippocampus to the effects of ethanol, suggesting a potential therapeutic role in treating alcohol dependence.

The study found that combining zonisamide with ethanol resulted in a synergistic effect on brain activity, indicating that caution is needed due to the enhanced depressive effects on the central nervous system.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A pharmaco-EEG-based assessment of the interaction between ethanol and zonisamide. Pietrzak, B., Zwierzyńska, E., Krupa, A.[2018]

Disulfiram (DSM) is an effective medication for alcohol de-addiction, with 76.5% of patients completing the treatment course and experiencing relatively low adverse drug reactions (ADRs), such as drowsiness and tiredness.

While DSM can alter liver function, indicated by significant changes in liver enzyme levels, the occurrence of ADRs did not significantly contribute to treatment dropouts, as patients often confused withdrawal symptoms with ADRs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Status of disulfiram in present day alcoholic deaddiction therapy. Palatty, PL., Saldanha, E.[2021]

In a 12-week pilot clinical trial involving 40 alcohol-dependent subjects, zonisamide significantly reduced heavy drinking days and overall alcohol consumption compared to placebo, indicating its potential efficacy in treating alcohol dependence.

Zonisamide was well tolerated with no serious adverse events reported, suggesting it is a safe option for individuals seeking treatment for alcohol dependence.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Placebo-controlled trial of zonisamide for the treatment of alcohol dependence. Arias, AJ., Feinn, R., Oncken, C., et al.[2021]

In a 13-week open-label trial with 16 alcohol-dependent subjects, zonisamide (400 mg daily) significantly reduced the mean daily alcohol consumption without impairing verbal fluency or cognitive performance.

Zonisamide was well tolerated by participants, suggesting it may be a safe option for reducing alcohol intake in individuals with alcohol dependence.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Open label trial of the tolerability and efficacy of zonisamide in the treatment of alcohol dependence. Knapp, CM., Sarid-Segal, O., Richardson, MA., et al.[2021]

In a 6-month trial involving 274 alcohol-dependent patients, amisulpride was found to be less effective than topiramate in reducing alcohol intake and cravings, but equally effective as naltrexone.

Patients taking amisulpride showed poorer results in measures of alcohol consumption compared to those on topiramate, indicating that while amisulpride can help, it may not be the best option compared to other treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Amisulpride for the treatment of alcohol dependence]. Flórez, G., Saiz, PA., García-Portilla, P., et al.[2018]

In a study of 151 adult patients with difficult-to-treat epilepsy, zonisamide (ZNS) as an adjunctive treatment showed a retention rate of 53.6% after 12 months, indicating its potential effectiveness for long-term use.

Patients experienced a mean reduction in seizure frequency of 27%, with the best results observed in those with focal and secondary generalized seizures, while the treatment was generally well-tolerated despite some CNS-related side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Retention rate of zonisamide in intractable epilepsy. Nakken, KO., Lindstrøm, P., Andersen, H.[2018]

Zonisamide has been shown to be effective in treating refractory partial seizures in adults, with doses of 300 mg/day or higher leading to significant reductions in seizure frequency, particularly at 500 mg/day where a 51% reduction was observed compared to placebo.

The drug has an excellent safety and tolerability profile, with most adverse events being mild to moderate and a low rate of discontinuation, making it a suitable option for patients when used alongside other antiepileptic medications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Zonisamide as adjunctive therapy for refractory partial seizures. Brodie, MJ.[2018]

Zonisamide is an effective broad-spectrum antiepileptic drug used as an adjunctive therapy for partial seizures, with multiple mechanisms of action that may also benefit conditions like headaches and neuropathic pain.

Since its introduction in Japan in 1989 and the USA in 2002, Zonisamide has shown promising efficacy in treating both focal and generalized epilepsy, making it a versatile option for various seizure and nonseizure disorders.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Zonisamide: newer antiepileptic agent with multiple mechanisms of action. Biton, V.[2019]

References

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

A pharmaco-EEG-based assessment of the interaction between ethanol and zonisamide. [2018]

2. India pubmed.ncbi.nlm.nih.gov

Status of disulfiram in present day alcoholic deaddiction therapy. [2021]

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

Placebo-controlled trial of zonisamide for the treatment of alcohol dependence. [2021]

4. England pubmed.ncbi.nlm.nih.gov

Open label trial of the tolerability and efficacy of zonisamide in the treatment of alcohol dependence. [2021]

5. Spain pubmed.ncbi.nlm.nih.gov

[Amisulpride for the treatment of alcohol dependence]. [2018]

6. Denmark pubmed.ncbi.nlm.nih.gov

Retention rate of zonisamide in intractable epilepsy. [2018]

7. Netherlands pubmed.ncbi.nlm.nih.gov

Zonisamide as adjunctive therapy for refractory partial seizures. [2018]

8. England pubmed.ncbi.nlm.nih.gov

Zonisamide: newer antiepileptic agent with multiple mechanisms of action. [2019]