Zonisamide Treatment of Alcohol Use Disorder: an Evaluation of Efficacy and Mechanism of Action

Alcohol Use Disorder Clinical Trial

— Z-Comp  

Official title:

Zonisamide Treatment of Alcohol Use Disorder: an Evaluation of Efficacy and Mechanism of Action

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02900352
• Other study ID #: HM20014185
• Secondary ID: 16050177007R01AA
• Status: Completed
• Phase: Phase 3
• Start date: October 2016
• Est. completion date: April 22, 2021

Study information

• Verified date: October 2022
• Source: Virginia Commonwealth University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 156
• Est. completion date: April 22, 2021
• Est. primary completion date: April 22, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 21 Years to 70 Years

Eligibility

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 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

Related Conditions & MeSH terms

• Alcohol Drinking
• Alcohol Use Disorder
• Alcoholism
• Disease

Intervention

Drug:
• Zonisamide
Titration of dose to 500mg oral, daily, over 8 weeks, then 7 weeks of treatment at that dose
• Placebo
Placebo

Locations

Country	Name	City	State
United States	UCONN Health	Farmington	Connecticut
United States	Yale University	New Haven	Connecticut
United States	Virginia Commonwealth University	Richmond	Virginia
United States	West Haven Veterans Affairs	West Haven	Connecticut

Sponsors (5)

Lead Sponsor	Collaborator
Virginia Commonwealth University	National Institute on Alcohol Abuse and Alcoholism (NIAAA), University of Connecticut, VA Connecticut Healthcare System, Yale University

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	over 8 weeks (weeks 9-16)
Secondary	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.	over the last 8 weeks (weeks 9-16)
Secondary	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.	over 16 weeks (weeks 1-16)
Secondary	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).	over the last 8 weeks (weeks 9-16)
Secondary	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	over 16 weeks (weeks 1-16) and at 2 week and 3 month follow up
Secondary	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	over 16 weeks (weeks 1-16) and at 2 week and 3 month follow up
Secondary	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	over 16 weeks (weeks 1-16) and at 2 week and 3 month follow up