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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial investigates whether the medication zonisamide (also known as Zonegran) can help reduce alcohol consumption. Researchers will compare zonisamide with a placebo (a pill with no active medicine) to determine its effectiveness in reducing alcohol use among adults seeking treatment for alcohol use disorder. Participants should have consumed four or more drinks on several recent occasions and be actively seeking help for their drinking habits. As a Phase 2 trial, this research focuses on assessing the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to important findings.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that zonisamide, a medication used to prevent seizures, is generally safe. A small initial study examined its safety for treating alcohol dependence and found that participants tolerated it well, with no major side effects reported. This suggests zonisamide is relatively safe. The FDA has approved zonisamide for treating seizures, indicating its safety is well-documented. However, people can react differently to medications. Always consult a healthcare professional before deciding to join a trial. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for alcoholism?

Unlike the standard treatments for alcoholism, which often involve medications like naltrexone, acamprosate, or disulfiram, zonisamide presents a novel approach by being an anticonvulsant that may help reduce alcohol cravings and consumption. Researchers are excited about zonisamide because it works by modulating glutamate and GABA neurotransmitter systems, offering a potentially different mechanism of action from existing therapies. This unique approach could provide an alternative for patients who do not respond well to current medications, offering hope for improved outcomes in managing alcohol dependence.

What evidence suggests that zonisamide might be an effective treatment for alcoholism?

Research has shown that zonisamide, which participants in this trial may receive, can help reduce alcohol consumption. One study found that participants drank fewer drinks each day on average. Another study demonstrated that zonisamide reduced alcohol intake in both animals and heavy drinkers. However, one study indicated that zonisamide was not more effective than other treatments in reducing daily drinking. Overall, zonisamide appears promising for those who want to cut down on drinking. Participants in this trial will receive either zonisamide plus standard treatment or a placebo plus standard treatment. ^{1 2 6 7 8}

Are You a Good Fit for This Trial?

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

Breath alcohol of 0.00 during informed consent

Ability to provide written 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 for a Trial Participant

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)

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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 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]

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, 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]

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]

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]

Citations

1. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0022395624005107

Results from a randomized controlled trial of zonisamide in ... Results showed a significant reduction in mean daily drinks consumed, with no notable changes in neuropsychological test performance. The authors also reported ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3157084/

Placebo-Controlled Trial of Zonisamide for the Treatment ... Zonisamide has also been shown to reduce alcohol intake in rodents and in risky drinkers in the context of a laboratory study. This pilot clinical trial ...

3. cdn.clinicaltrials.gov cdn.clinicaltrials.gov/large-docs/52/NCT02900352/Prot_SAP_000.pdf

Title: Zonisamide Treatment of Alcohol Use Disorder: an ... Purpose: To comprehensively evaluate the efficacy of an anticonvulsant medication zonisamide (ZNS) for the treatment of alcohol dependence in civilians.

4. horizonscandb.pcori.org horizonscandb.pcori.org/report/topics/89

Zonisamide (Zonegran) to treat alcohol use disorder Approved medications to treat AUD have shown limited effectiveness, and only one-third of patients achieve full remission with available therapies. Although the ...

5. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39306870/

Results from a randomized controlled trial of zonisamide in the ... Study findings indicate that ZON combined with TC does not demonstrate superior effectiveness for reducing average daily drinks in this clinical sample.

6. neurology.org neurology.org/doi/10.1212/CPJ.0000000000200210

Zonisamide | Neurology Clinical Practice A 12-week study of veterans diagnosed with AUD and PTSD revealed that drinking significantly decreased in patients taking ZNS 400 mg/d. ZNS ...

7. centerwatch.com centerwatch.com/clinical-trials/listings/NCT02901041/interdisciplinary-study-of-a-novel-anticonvulsant-in-alcoholism

Interdisciplinary Study of A Novel Anticonvulsant in ... Zonisamide (ZON), a broad spectrum anticonvulsant, has proven to be more effective than a placebo in reducing alcohol intake in individuals ...

8. academic.oup.com academic.oup.com/alcalc/article/52/3/282/3001988

Impact of Zonisamide on the Development ... - Oxford Academic This study uses a pharmaco-EEG method to examine the impact of zonisamide on the development and course of alcohol dependence in rabbits.