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Zonisamide Treatment of Alcohol Use Disorder: an Evaluation of Efficacy and Mechanism of Action (Z-Comp)

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ClinicalTrials.gov Identifier: NCT02900352
Recruitment Status : Recruiting
First Posted : September 14, 2016
Last Update Posted : August 12, 2019
Sponsor:
Collaborators:
University of Connecticut
Yale University
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
VA Connecticut Healthcare System
Information provided by (Responsible Party):
Virginia Commonwealth University

Brief Summary:
This is a randomized, placebo-controlled, double-blind, 16 week trial of the medication zonisamide for the treatment of heavy drinking alcoholic civilians.

Condition or disease Intervention/treatment Phase
Alcohol Use Disorder Drug: Zonisamide Drug: Placebo Phase 1

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 160 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Zonisamide Treatment of Alcohol Use Disorder: an Evaluation of Efficacy and Mechanism of Action
Study Start Date : October 2016
Estimated Primary Completion Date : March 2021
Estimated Study Completion Date : March 2021

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Alcohol
Drug Information available for: Zonisamide

Arm Intervention/treatment
Experimental: Zonisamide
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.
Drug: Zonisamide
Titration of dose to 500mg oral, daily, over 8 weeks, then 7 weeks of treatment at that dose

Placebo Comparator: Placebo
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)
Drug: Placebo
Placebo




Primary Outcome Measures :
  1. Change in 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.


Secondary Outcome Measures :
  1. PSNHDD [ Time Frame: over 8 weeks (weeks 9-16) ]
    percentage of subjects with no heavy drinking days (PSNHDD) The PSNHDD can be derived from each subject's TLFB data.

  2. Change in Gamma glutamyl transferase (GGT) [ Time Frame: over 16 weeks (weeks 1-16) ]
    Difference between groups on change in levels of 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).

  3. Change in number of heavy drinking days per week [ Time Frame: over 16 weeks (weeks 9-16) ]
    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).

  4. Change in Alcohol Urge Questionnaire Score (AUQ) [ Time Frame: over 16 weeks (weeks 1-16) ]
    This is the change in AUQ scores (urge to drink) measured weekly compared between groups using repeated measures

  5. Change in quality of life [ Time Frame: over 16 weeks (weeks 1-16) ]
    Change in quality of life scores measured by the Q-LES-Q

  6. Changes in level of alcohol-related problems [ Time Frame: over 16 weeks (weeks 1-16) ]
    Change in level of alcohol-related problems measured by the Short Index of Problems (SIP)



Information from the National Library of Medicine

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Ages Eligible for Study:   21 Years to 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • 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 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02900352


Contacts
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Contact: Albert Arias, MD 203-932-5711 ext 8155 albert.arias@vcuhealth.org

Locations
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United States, Connecticut
UCONN Health Active, not recruiting
Farmington, Connecticut, United States, 06030
Yale University Completed
New Haven, Connecticut, United States, 06520
West Haven Veterans Affairs Active, not recruiting
West Haven, Connecticut, United States, 06515
United States, Virginia
Virginia Commonwealth University Recruiting
Richmond, Virginia, United States, 23298
Contact: Albert Arias, MD       albert.arias@vcuhealth.org   
Sponsors and Collaborators
Virginia Commonwealth University
University of Connecticut
Yale University
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
VA Connecticut Healthcare System
Investigators
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Principal Investigator: Albert Arias, MD Virginia Commonwealth University

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Responsible Party: Virginia Commonwealth University
ClinicalTrials.gov Identifier: NCT02900352     History of Changes
Other Study ID Numbers: HM20014185
1605017700 ( Other Identifier: Yale University )
7R01AA024466-04 ( U.S. NIH Grant/Contract )
First Posted: September 14, 2016    Key Record Dates
Last Update Posted: August 12, 2019
Last Verified: August 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Keywords provided by Virginia Commonwealth University:
Alcohol Use Disorder
Alcoholism
Alcohol Dependence
Zonisamide
Alcohol Intoxication
Drinking Behaviors
Anticonvulsants
Additional relevant MeSH terms:
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Disease
Alcoholism
Alcohol Drinking
Pathologic Processes
Drinking Behavior
Alcohol-Related Disorders
Substance-Related Disorders
Chemically-Induced Disorders
Mental Disorders
Ethanol
Zonisamide
Anti-Infective Agents, Local
Anti-Infective Agents
Central Nervous System Depressants
Physiological Effects of Drugs
Anticonvulsants
Calcium Channel Blockers
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Calcium-Regulating Hormones and Agents