Alcohol Use DisorderPhase 3Z-CompNCT02900352
Zonisamide Treatment of Alcohol Use Disorder: an Evaluation of Efficacy and Mechanism of Action
A Phase 3 study testing Zonisamide in people with Alcohol Use Disorder, run by Virginia Commonwealth University at 4 sites in United States.
Trial summary
This is a randomized, placebo-controlled, double-blind, 16 week trial of the medication zonisamide for the treatment of heavy drinking alcoholic civilians. Read more about this study
- Who is it for?
- Ages 21 to 70 years
- Conditions the study is for
- Alcohol Use Disorder
- What is being tested?
- Zonisamide
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 156 participants
- Where
- 4 sitesUnited States
- Study dates
- Oct 2016to 22 Apr 2021
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 21 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Female/male aged 21-70 years
- Regular heavy drinkers as defined by averaging 2 heavy drinking days per week over 90 days baseline pre-treatment timeline follow-back (TLFB), and current DSM-IV-TR alcohol dependence that recognize a need to reduce or stop drinking (Note: heavy drinking days will be defined as follows; for men greater than or equal to 5 drinks in a day and for women greater than or equal to 4 drinks in a day)
- Women of child-bearing potential (i.e., no hysterectomy, bilateral oophorectomy, or tubal ligation or <2 years postmenopausal), must be non-lactating, practicing a reliable method of birth control, and have a negative serum pregnancy test prior to initiation of treatment;
- Willingness to provide signed, informed consent to participate in the study
Who cannot join
- A current, clinically significant physical disease or abnormality (i.e., neurologic, renal, rheumatologic, gastrointestinal, hematologic, pulmonary, endocrine, cardiovascular, hepatic, or autoimmune disease that, in the context of the study would represent a risk to the subject, or significant laboratory abnormalities such as hepatic aminotransferase levels (i.e., AST and ALT) greater than 300% of the upper limit of normal or direct bilirubin levels >150% of the upper limit of normal) on the basis of medical history, physical examination, or routine laboratory evaluation. Other specific exclusionary disorders include;
- History of clinically significant renal calculi or renal failure; a significant indication of renal compromise will be defined by an elevation of serum creatinine above the investigators' laboratory's limit of normal, or a known history of renal failure or chronic renal disease, or any current or chronic disease that could reasonably be expected to result in renal failure
- History of hypersensitivity to ZNS or any sulfonamide, Stevens-Johnson Syndrome, penicillin allergy, or history of any severe drug allergic reaction; History of systemic autoimmune disease such as lupus erythematosis, fibromyalgia, or rheumatoid arthritis;
- Current blood dyscrasia or a history of such, with the exception of a past history of iron deficiency anemia
- History of seizure disorder
- Use of any of a number of medications that might prominently influence drinking patterns or cause risk of harm or injury (e.g., topiramate, disulfiram, naltrexone, acetazolamide, stimulants such as amphetamine, or tramadol; Schizophrenia, bipolar disorder, PTSD, or substantial suicide or violence risk (i.e., can't be managed safely in the outpatient setting) on the basis of history or psychiatric examination; j) currently dependent on opioids or benzodiazepines or other sedatives
- Considered by the investigators to be clinically inappropriate for study participation or have participated in another pharmacotherapy study in the past thirty days
- Subjects with prominent signs of physical dependence, and/or medical comorbidities such that study physicians feel they should consider immediate detoxification, and referred for medical detoxification in a normal treatment setting
Trial locations and contacts
4 sites in 1 country.
United States4 sites
UCONN Health
Farmington, Connecticut, 06030
Yale University
New Haven, Connecticut, 06520
Virginia Commonwealth University
Richmond, Virginia, 23298
West Haven Veterans Affairs
West Haven, Connecticut, 06515
About this study
This is a randomized, placebo-controlled, double-blind, 16 week trial of the medication zonisamide for the treatment of heavy drinking alcoholic civilians.
Read the detailed description
This is a 16-week randomized, double blind, placebo-controlled trial designed to determine the effectiveness of zonisamide treatment for reducing heavy drinking and overall drinking in 160 treatment-seeking, regularly heavy drinking, alcohol-dependent civilians who want to quit drinking or reduce consumption to non-hazardous levels. The investigators will use state-of-the-art methodology and outcome assessments, including medical management (MM) therapy (a minimal behavioral intervention aimed at reinforcing treatment goals and adherence to medication), which is simple and easily implemented in primary care settings. The use of MM in the study will increase the generalizability of results, allowing a more accurate assessment of zonisamide's effectiveness than if a more intensive behavioral intervention were to be used. To demonstrate zonisamide's effectiveness in a representative civilian sample, the investigators will include civilians with co-morbid mood and anxiety disorders.
- Conditions
- Alcohol Use Disorder
- Being tested
- Zonisamide, Placebo
- Keywords
- Alcohol Use Disorder, Alcoholism, Alcohol Dependence, Zonisamide, Alcohol Intoxication, Drinking Behaviors, Anticonvulsants
- Medical subject headings
- Alcoholism, Alcoholic Intoxication, Drinking Behavior
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ZonisamideDrug
Also called Brand name: Zonegran
Titration of dose to 500mg oral, daily, over 8 weeks, then 7 weeks of treatment at that dose
PlaceboDrug
Also called Brand name: Zonegran
Placebo
| Study group | Role | What they receive |
|---|---|---|
| Zonisamide | Experimental | Subjects will receive zonisamide titrated to a target dose of 500mg orally, daily, double-blind (Titration of dose to 500mg oral, daily, over 7 weeks, then 9 weeks of treatment at that dose). Subjects may increase their dose to 600mg daily during the target treatment period if it is thought to be beneficial. Receives: Drug: Zonisamide |
| Placebo | Placebo comparator | Patients will receive placebo pills that are made to match the zonisamide medication (via over-encapsulation, double-blind, subjects will receive same number of capsules as the active medication group) Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Drinks Per Week
Difference between groups in the number of total standard drinks per week over 8 weeks (weeks 9-16, the weeks on the target dose) performed using a mixed models longitudinal analysis.
Measured: over 8 weeks (weeks 9-16)
Secondary outcomes (6)
Percentage of Subjects With No Heavy Drinking Days
percentage of subjects with no heavy drinking days (PSNHDD) The PSNHDD can be derived from each subject's Timeline Followback (TLFB) data.
Measured: over the last 8 weeks (weeks 9-16)
Gamma Glutamyl Transferase (GGT) Levels
Difference between groups on levels of GGT over time from baseline to endpoint, which will includes two interim data points for a total of four time points. This will analyzed with a mixed models longitudinal analysis (repeated measures). Levels are in Units per Liter.
Measured: over 16 weeks (weeks 1-16)
Number of Heavy Drinking Days Per Week
The difference in the number of heavy drinking days per week compared between groups (zonisamide and placebo) for the last 8 weeks of treatment (during the time spent on the target dose of the medication). Performed using a mixed models longitudinal analysis (repeated measures).
Measured: over the last 8 weeks (weeks 9-16)
Change in Alcohol Urge Questionnaire Score (AUQ)
This is the change in AUQ scores (urge to drink) measured weekly compared between groups using repeated measures
Min value: 8 Max value: 42 higher score = worse craving
Measured: over 16 weeks (weeks 1-16) and at 2 week and 3 month follow up
Change in Quality of Life
Change in quality of life scores measured by the Q-LES-Q. ' Min: 16 Max: 80 Higher Scores = Higher Life Enjoyment
Measured: over 16 weeks (weeks 1-16) and at 2 week and 3 month follow up
Level of Alcohol-related Problems
level of alcohol-related problems measured by the Short Index of Problems (SIP), total score
Min score: 0 Max Score: 45 Higher score= more problems
Measured: over 16 weeks (weeks 1-16) and at 2 week and 3 month follow up
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Sep 2016 (estimated)
- Study startOct 2016
- Primary completion22 Apr 2021
- Study completion22 Apr 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Alcohol Use DisorderStudies of the same condition, open and under way.
- More trials run by Virginia Commonwealth UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 156 participants (actual)
Sponsor and investigators
- Lead sponsor
- Virginia Commonwealth University
- Sponsor type
- University, hospital or other
- Collaborators
- University of Connecticut, Yale University, National Institute on Alcohol Abuse and Alcoholism (NIAAA), VA Connecticut Healthcare System
- Responsible party
- Sponsor
- Investigators
- Albert Arias, MD, Principal investigator, Virginia Commonwealth University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02900352
- Sponsor's protocol ID
- HM20014185
- Other IDs
- 1605017700, 7R01AA024466-04
- Acronym
- Z-Comp
- Status last verified
- Oct 2022
- First submitted
- 9 Sep 2016
- Last updated
- 13 Oct 2022
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 13 Oct 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Zonisamide Treatment of Alcohol Use Disorder: an Evaluation of Efficacy and Mechanism of Action
- ClinicalTrials.gov ID
- NCT02900352
- Acronym / sponsor ID
- Z-Comp / HM20014185
- Conditions
- Alcohol Use Disorder
- Keywords
- Alcohol Use Disorder, Alcoholism, Alcohol Dependence, Zonisamide, Alcohol Intoxication, Drinking Behaviors, Anticonvulsants
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 156 participants (actual)
- Lead sponsor
- Virginia Commonwealth UniversityUniversity, hospital or other
- Collaborators
- University of Connecticut, Yale University, National Institute on Alcohol Abuse and Alcoholism (NIAAA), VA Connecticut Healthcare System
- Study start
- Oct 2016
- Primary completion
- 22 Apr 2021 (actual)
- Study completion
- 22 Apr 2021 (actual)
- First posted
- 14 Sep 2016 (estimated)
- Results
- Posted 13 Oct 2022
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a randomized, placebo-controlled, double-blind, 16 week trial of the medication zonisamide for the treatment of heavy drinking alcoholic civilians.
Detailed description
This is a 16-week randomized, double blind, placebo-controlled trial designed to determine the effectiveness of zonisamide treatment for reducing heavy drinking and overall drinking in 160 treatment-seeking, regularly heavy drinking, alcohol-dependent civilians who want to quit drinking or reduce consumption to non-hazardous levels. The investigators will use state-of-the-art methodology and outcome assessments, including medical management (MM) therapy (a minimal behavioral intervention aimed at reinforcing treatment goals and adherence to medication), which is simple and easily implemented in primary care settings. The use of MM in the study will increase the generalizability of results, allowing a more accurate assessment of zonisamide's effectiveness than if a more intensive behavioral intervention were to be used. To demonstrate zonisamide's effectiveness in a representative civilian sample, the investigators will include civilians with co-morbid mood and anxiety disorders.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Zonisamide | Experimental | Drug: ZonisamideSubjects will receive zonisamide titrated to a target dose of 500mg orally, daily, double-blind (Titration of dose to 500mg oral, daily, over 7 weeks, then 9 weeks of treatment at that dose). Subjects may increase their dose to 600mg daily during the target treatment period if it is thought to be beneficial. |
| Placebo | Placebo comparator | Drug: PlaceboPatients will receive placebo pills that are made to match the zonisamide medication (via over-encapsulation, double-blind, subjects will receive same number of capsules as the active medication group) |
Who may qualify
- Ages
- 21 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Female/male aged 21-70 years
- Regular heavy drinkers as defined by averaging 2 heavy drinking days per week over 90 days baseline pre-treatment timeline follow-back (TLFB), and current DSM-IV-TR alcohol dependence that recognize a need to reduce or stop drinking (Note: heavy drinking days will be defined as follows; for men greater than or equal to 5 drinks in a day and for women greater than or equal to 4 drinks in a day)
- Women of child-bearing potential (i.e., no hysterectomy, bilateral oophorectomy, or tubal ligation or <2 years postmenopausal), must be non-lactating, practicing a reliable method of birth control, and have a negative serum pregnancy test prior to initiation of treatment;
- Willingness to provide signed, informed consent to participate in the study
Key exclusion criteria (8 listed)
- A current, clinically significant physical disease or abnormality (i.e., neurologic, renal, rheumatologic, gastrointestinal, hematologic, pulmonary, endocrine, cardiovascular, hepatic, or autoimmune disease that, in the context of the study would represent a risk to the subject, or significant laboratory abnormalities such as hepatic aminotransferase levels (i.e., AST and ALT) greater than 300% of the upper limit of normal or direct bilirubin levels >150% of the upper limit of normal) on the basis of medical history, physical examination, or routine laboratory evaluation. Other specific exclusionary disorders include;
- History of clinically significant renal calculi or renal failure; a significant indication of renal compromise will be defined by an elevation of serum creatinine above the investigators' laboratory's limit of normal, or a known history of renal failure or chronic renal disease, or any current or chronic disease that could reasonably be expected to result in renal failure
- History of hypersensitivity to ZNS or any sulfonamide, Stevens-Johnson Syndrome, penicillin allergy, or history of any severe drug allergic reaction; History of systemic autoimmune disease such as lupus erythematosis, fibromyalgia, or rheumatoid arthritis;
- Current blood dyscrasia or a history of such, with the exception of a past history of iron deficiency anemia
- History of seizure disorder
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ZonisamideAlso: Brand name: ZonegranTitration of dose to 500mg oral, daily, over 8 weeks, then 7 weeks of treatment at that dose | Drug | Zonisamide |
| PlaceboAlso: Brand name: ZonegranPlacebo | Drug | Placebo |
Primary outcome
Number of Drinks Per Week
Time frame: over 8 weeks (weeks 9-16)
Difference between groups in the number of total standard drinks per week over 8 weeks (weeks 9-16, the weeks on the target dose) performed using a mixed models longitudinal analysis.
6 secondary outcomes
Percentage of Subjects With No Heavy Drinking Days
Time frame: over the last 8 weeks (weeks 9-16)
Gamma Glutamyl Transferase (GGT) Levels
Time frame: over 16 weeks (weeks 1-16)
Number of Heavy Drinking Days Per Week
Time frame: over the last 8 weeks (weeks 9-16)
Change in Alcohol Urge Questionnaire Score (AUQ)
Time frame: over 16 weeks (weeks 1-16) and at 2 week and 3 month follow up
Change in Quality of Life
Time frame: over 16 weeks (weeks 1-16) and at 2 week and 3 month follow up
Level of Alcohol-related Problems
Time frame: over 16 weeks (weeks 1-16) and at 2 week and 3 month follow up
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Oct 2022.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Albert Arias, MD principal investigator
Virginia Commonwealth University
4 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Zonisamide in people with Alcohol Use Disorder, run by Virginia Commonwealth University at 4 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 13 Oct 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 13 Oct 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Drinks Per Week (time frame: over 8 weeks (weeks 9-16)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Oct 2022.