Alcohol Use DisorderPhase 3NCT02368431
Effectiveness of Zonisamide in Alcohol Dependent Veterans
A Phase 3 study testing Zonisamide in people with Alcohol Use Disorder, run by VA Office of Research and Development at 1 site 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 Veterans. 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
- 92 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Mar 2015to 1 Oct 2018
- 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 veterans 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 alcohol dependence diagnosis by the Diagnostic and Statistical Manual IV Text Revision (DSM-IV-TR) 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., aspartate aminotransferase (AST) and alanine aminotransferase (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 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 zonisamide 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
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- 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, posttraumatic stress 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
1 site in 1 country.
United States1 site
VA Connecticut Healthcare System West Haven Campus, West Haven, CT
West Haven, Connecticut, 06516
About this study
Official title: Effectiveness of Zonisamide in the Treatment of Alcohol Dependent Veterans
This is a randomized, placebo-controlled, double-blind, 16 week trial of the medication zonisamide for the treatment of heavy drinking alcoholic Veterans.
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 Veterans 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 Veteran sample, the investigators will include Veterans with co-morbid mood and anxiety disorders.
The investigators also plan to explore the interaction between genotype and medication on drinking outcomes.
- Conditions
- Alcohol Use Disorder
- Being tested
- Zonisamide, Placebo
- Keywords
- Alcohol Use Disorder, Alcoholism, Alcohol Dependence, Zonisamide, Alcoholic 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 Zonegran
Titration of dose to 500mg oral, daily, over 8 weeks, then 7 weeks of treatment at that dose
PlaceboDrug
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 8 weeks, then 7 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 (PSNHDD)
Percentage of Subjects with No Heavy Drinking Days (PSNHDD) The PSNHDD can be derived from each subject's timeline follow back (TLFB) data.
Measured: Baseline
Gamma Glutamyl Transferase (GGT)
Difference between groups on change in levels of Gamma glutamyl transferase (GGT) over time from baseline to endpoint, which will include several interim data points. This will analyzed with a mixed models longitudinal analysis (repeated measures). Normal range for GGT levels are 10 U/L - 65 U/L - above 65 U/L above 65 U/L is considered a high GGT level
Measured: Baseline, Week 4, 8 and 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) during the time spent on the target dose of the medication. Performed using a mixed models longitudinal analysis (repeated measures).
Measured: over 16 weeks (weeks 1-16)
Alcohol Urge Questionnaire Score (AUQ)
This is the change in AUQ scores (urge to drink) measured weekly compared between groups using repeated measures. The AUQ is a 8 item participant rated questionnaire. Participants indicate how much they agree or disagree with the statements by selecting one number, 1 strongly disagree through 7 strongly agree. Participants can scores between 8 (lowest) - 56 (highest), the higher the score the more urge to drink.
Measured: over 16 weeks (weeks 1-16)
Change in Quality of Life
Change in quality of life scores measured by the Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q). The Q-LES-Q is a 16 item participant rated questionnaire. Participants indicate how they are feeling over the 16 item from Very poor (1), Poor (2), Fair (3), Good (4), and Very Good (5). Participants can scores between 14 (lowest) - 70 (highest) the higher the score more satisfied with quality of life.
Measured: Over 16 weeks (Baseline and 16 weeks)
Level of Alcohol-related Problems (SIP)
Change in level of alcohol-related problems measured by the Short Index of Problems (SIP). The SIP is a 15 item participant rated questionnaire. Participants rate the number of events that drinkers sometimes experience. Participants indicate how often each of the items has happened. They are scored by selecting one number, 0 Never; 1 Once or a few times; 2 Once or twice a week; 3 Daily or almost daily. Participants can scores between 0 (lowest) - 45 (highest) - the higher score the more drinking problems.
Measured: over 16 weeks (Baseline and Week 16)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Feb 2015 (estimated)
- Study start1 Mar 2015
- Primary completion1 Oct 2018
- Study completion1 Oct 2018
Why it stopped: Funding ended prematurely
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 VA Office of Research and DevelopmentThe 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
- 92 participants (actual)
Sponsor and investigators
- Lead sponsor
- VA Office of Research and Development
- Sponsor type
- US federal agency
- Responsible party
- Sponsor
- Investigators
- Albert J Arias, MD, Principal investigator, VA Connecticut Healthcare System West Haven Campus, West Haven, CT
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02368431
- Sponsor's protocol ID
- CLNA-003-14S
- Other IDs
- ICX001012A
- Status last verified
- Dec 2020
- First submitted
- 14 Feb 2015
- Last updated
- 7 Dec 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 7 Dec 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effectiveness of Zonisamide in the Treatment of Alcohol Dependent Veterans
- ClinicalTrials.gov ID
- NCT02368431
- Acronym / sponsor ID
- CLNA-003-14S
- Conditions
- Alcohol Use Disorder
- Keywords
- Alcohol Use Disorder, Alcoholism, Alcohol Dependence, Zonisamide, Alcoholic Intoxication, Drinking Behaviors, Anticonvulsants
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Funding ended prematurely
- Enrolment
- 92 participants (actual)
- Lead sponsor
- VA Office of Research and DevelopmentUS federal agency
- Study start
- 1 Mar 2015 (actual)
- Primary completion
- 1 Oct 2018 (actual)
- Study completion
- 1 Oct 2018 (actual)
- First posted
- 23 Feb 2015 (estimated)
- Results
- Posted 2 Jun 2020
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 Veterans.
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 Veterans 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 Veteran sample, the investigators will include Veterans with co-morbid mood and anxiety disorders.
The investigators also plan to explore the interaction between genotype and medication on drinking outcomes.
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 8 weeks, then 7 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 veterans 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 alcohol dependence diagnosis by the Diagnostic and Statistical Manual IV Text Revision (DSM-IV-TR) 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 (10 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., aspartate aminotransferase (AST) and alanine aminotransferase (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 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 zonisamide 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
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: ZonegranTitration of dose to 500mg oral, daily, over 8 weeks, then 7 weeks of treatment at that dose | Drug | Zonisamide |
| PlaceboPlacebo | 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 (PSNHDD)
Time frame: Baseline
Gamma Glutamyl Transferase (GGT)
Time frame: Baseline, Week 4, 8 and 16
Number of Heavy Drinking Days Per Week
Time frame: over 16 weeks (weeks 1-16)
Alcohol Urge Questionnaire Score (AUQ)
Time frame: over 16 weeks (weeks 1-16)
Change in Quality of Life
Time frame: Over 16 weeks (Baseline and 16 weeks)
Level of Alcohol-related Problems (SIP)
Time frame: over 16 weeks (Baseline and Week 16)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Dec 2020.
- 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 J Arias, MD principal investigator
VA Connecticut Healthcare System West Haven Campus, West Haven, CT
1 site 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 VA Office of Research and Development at 1 site 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 10 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: stopped early, as of the sponsor's last update on 7 Dec 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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 2 Jun 2020). 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 7 Dec 2020.