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| ID | Type | Description | Link |
|---|---|---|---|
| 1605017700 | Other Identifier | Yale University | |
| 7R01AA024466-04 | U.S. NIH Grant/Contract | View source |
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| Name | Class |
|---|---|
| University of Connecticut | OTHER |
| Yale University | OTHER |
| National Institute on Alcohol Abuse and Alcoholism (NIAAA) | NIH |
| VA Connecticut Healthcare System |
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This is a randomized, placebo-controlled, double-blind, 16 week trial of the medication zonisamide for the treatment of heavy drinking alcoholic civilians.
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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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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. |
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| 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) |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Zonisamide | Drug | Titration of dose to 500mg oral, daily, over 8 weeks, then 7 weeks of treatment at that dose |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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) |
| Measure | Description | Time Frame |
|---|---|---|
| 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) |
| Gamma Glutamyl Transferase (GGT) Levels |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Albert Arias, MD | Virginia Commonwealth University | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| UCONN Health | Farmington | Connecticut | 06030 | United States | ||
| Yale University |
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| ID | Title | Description |
|---|---|---|
| FG000 | Zonisamide | 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. Zonisamide: Titration of dose to 500mg oral, daily, over 8 weeks, then 7 weeks of treatment at that dose |
| FG001 | 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) Placebo: Placebo |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
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Alcohol Use Disorder Treatment Seekers
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| ID | Title | Description |
|---|---|---|
| BG000 | 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. Zonisamide: Titration of dose to 500mg oral, daily, over 8 weeks, then 7 weeks of treatment at that dose |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 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. | Posted | Mean | Standard Error | Number of drinks per week | over 8 weeks (weeks 9-16) |
|
Duration of the study (16 weeks)
Patients provided subjective reports of side effects at each study visit using the Systematic Assessment for Treatment Emergent Effects (SAFTEE) interview, a widely used measure of adverse events. Complex adverse events may have also been recorded using non-systematic methods
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | 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. Zonisamide: Titration of dose to 500mg oral, daily, over 8 weeks, then 7 weeks of treatment at that dose |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Stroke | Cardiac disorders | Non-systematic Assessment | 1 participant (ppt) experienced stroke during study. Medication was tapered, blind was broken, ppt was withdrawn from study. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Abdominal Pain | Gastrointestinal disorders | SAFTEE | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Albert Arias | Virginia Commonwealth University | 8048285793 | albert.arias@vcuhealth.org |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Jun 5, 2020 | Apr 18, 2022 | Prot_SAP_000.pdf |
| ICF | No | No | Yes | Informed Consent Form | Jul 10, 2020 | Apr 18, 2022 | ICF_001.pdf |
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| ID | Term |
|---|---|
| D000437 | Alcoholism |
| D000435 | Alcoholic Intoxication |
| D004327 | Drinking Behavior |
| ID | Term |
|---|---|
| D019973 | Alcohol-Related Disorders |
| D019966 | Substance-Related Disorders |
| D064419 | Chemically-Induced Disorders |
| D001523 | Mental Disorders |
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| ID | Term |
|---|---|
| D000078305 | Zonisamide |
| ID | Term |
|---|---|
| D013449 | Sulfonamides |
| D000577 | Amides |
| D009930 | Organic Chemicals |
| D013450 | Sulfones |
| D013457 |
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| FED |
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| Placebo | Drug | Placebo |
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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) |
| 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) |
| 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 |
| 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 |
| 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 |
| New Haven |
| Connecticut |
| 06520 |
| United States |
| West Haven Veterans Affairs | West Haven | Connecticut | 06515 | United States |
| Virginia Commonwealth University | Richmond | Virginia | 23298 | United States |
| BG001 | 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) Placebo: Placebo |
| BG002 | Total | Total of all reporting groups |
| years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Ethnicity (NIH/OMB) | Count of Participants | Participants |
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| Race (NIH/OMB) | Count of Participants | Participants |
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| Region of Enrollment | Number | participants |
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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) Placebo: Placebo |
|
|
|
| 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. | Posted | Number | Percentage of participants | over the last 8 weeks (weeks 9-16) |
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| 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. | Due to protocol changes over the course of the study, data for some outcomes was not collected for all participants or collected at slightly different timepoints. Results are reported for all participants for whom data is available. | Posted | Mean | Standard Error | International Units per Liter (UI/L) | 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). | Due to protocol changes over the course of the study, data for some outcomes was not collected for all participants. Results are reported for all participants for whom data is available. | Posted | Mean | Standard Error | Number of heavy drinking days/week | 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 | Due to protocol changes over the course of the study, data for some outcomes was not collected for all participants. Results are reported for all participants for whom data is available. | Posted | Mean | Standard Deviation | score on a scale | over 16 weeks (weeks 1-16) and at 2 week and 3 month follow up |
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|
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| 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 | Due to protocol changes over the course of the study, data for some outcomes was not collected for all participants. Results are reported for all participants for whom data is available. | Posted | Mean | Standard Error | score on a scale | over 16 weeks (weeks 1-16) and at 2 week and 3 month follow up |
|
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|
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| 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 | Due to protocol changes over the course of the study, data for some outcomes was not collected for all participants. Results are reported for all participants for whom data is available. | Posted | Mean | Standard Error | score on a scale | over 16 weeks (weeks 1-16) and at 2 week and 3 month follow up |
|
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|
|
| 0 |
| 77 |
| 2 |
| 77 |
| 73 |
| 77 |
| EG001 | 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) Placebo: Placebo | 1 | 79 | 2 | 79 | 76 | 79 |
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| Alcohol Withdrawal | Psychiatric disorders | Non-systematic Assessment | 1 ppt had voluntarily requested treatment for detoxification. Ppt was admitted to 5 day inpatient alcohol detox. |
|
| Motor Vehicle Accident | Injury, poisoning and procedural complications | Non-systematic Assessment | 1 ppt died in MVA while travelling out of state. Not study related and was on placebo. This incident was reported to the UConn IRB and Dr. Arias |
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| Suicidal Ideation | Psychiatric disorders | Non-systematic Assessment | 1 ppt contacted study team to report suicidal ideation and possible attempt, they were assessed at a hospital and discharged home, were tapered off study medication and follow-up engaged in outpatient clinic. |
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| Nausea | Gastrointestinal disorders | SAFTEE | Systematic Assessment |
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| Vomiting | Gastrointestinal disorders | SAFTEE | Systematic Assessment |
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| Extreme Tiredness | Nervous system disorders | SAFTEE | Systematic Assessment |
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| Constipation | Gastrointestinal disorders | SAFTEE | Systematic Assessment |
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| Diarrhea | Gastrointestinal disorders | SAFTEE | Systematic Assessment |
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| Nervousness | Psychiatric disorders | SAFTEE | Systematic Assessment |
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| Feeling Drowsy | Psychiatric disorders | SAFTEE | Systematic Assessment |
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| Fatigue | Psychiatric disorders | SAFTEE | Systematic Assessment |
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| Depressed Mood | Psychiatric disorders | SAFTEE | Systematic Assessment |
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| Swelling or Puffiness | Skin and subcutaneous tissue disorders | SAFTEE | Systematic Assessment |
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| Nasal Congestion/Runny Nose | Respiratory, thoracic and mediastinal disorders | SAFTEE | Systematic Assessment |
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| Rash or Skin Problem | Skin and subcutaneous tissue disorders | SAFTEE | Systematic Assessment |
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| Ringing in Ears | Nervous system disorders | SAFTEE | Systematic Assessment |
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| Decreased Sex Drive | Reproductive system and breast disorders | SAFTEE | Systematic Assessment |
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| Impotence | Reproductive system and breast disorders | SAFTEE | Systematic Assessment |
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| Headache | Nervous system disorders | SAFTEE | Systematic Assessment |
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| Blurred Vision | Eye disorders | SAFTEE | Systematic Assessment |
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| Gas | Gastrointestinal disorders | SAFTEE | Systematic Assessment |
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| Feeling dizzy, faint, lightheaded | Nervous system disorders | SAFTEE | Systematic Assessment |
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| Back, Muscle, or Bone Pain | Musculoskeletal and connective tissue disorders | SAFTEE | Systematic Assessment |
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| Mood Swings | Psychiatric disorders | SAFTEE | Systematic Assessment |
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| Shortness of Breath | Respiratory, thoracic and mediastinal disorders | SAFTEE | Systematic Assessment |
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| Loss of Appetite | Gastrointestinal disorders | SAFTEE | Systematic Assessment |
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| Difficulty Sleeping | Psychiatric disorders | SAFTEE | Systematic Assessment |
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| Teary or Dry Eyes | Eye disorders | SAFTEE | Systematic Assessment |
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| Extreme Thirst | Gastrointestinal disorders | SAFTEE | Systematic Assessment |
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| Heartburn | Gastrointestinal disorders | SAFTEE | Systematic Assessment |
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| Memory Problems | Psychiatric disorders | SAFTEE | Systematic Assessment |
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| Difficulty concentrating or paying attention | Pregnancy, puerperium and perinatal conditions | SAFTEE | Systematic Assessment |
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| Numbness or Tingling around Mouth, Fingers, or Toes | Nervous system disorders | SAFTEE | Systematic Assessment |
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| Swelling of Feet or Ankles | Skin and subcutaneous tissue disorders | SAFTEE | Systematic Assessment |
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| Restlessness, Can't sit still | Psychiatric disorders | SAFTEE | Systematic Assessment |
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| Anger or Irritability | Psychiatric disorders | SAFTEE | Systematic Assessment |
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| Leg Cramps | Musculoskeletal and connective tissue disorders | SAFTEE | Systematic Assessment |
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| Itching | Skin and subcutaneous tissue disorders | SAFTEE | Systematic Assessment |
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| Dry Mouth | Gastrointestinal disorders | SAFTEE | Systematic Assessment |
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| Unusual Sensations on Skin | Nervous system disorders | SAFTEE | Systematic Assessment |
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| Fever | General disorders | SAFTEE | Systematic Assessment |
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| Chills | General disorders | SAFTEE | Systematic Assessment |
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| Problems with Urination | Renal and urinary disorders | SAFTEE | Systematic Assessment |
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| Gas | Gastrointestinal disorders | SAFTEE | Systematic Assessment |
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| Irregular Heartbeat | Cardiac disorders | SAFTEE | Systematic Assessment |
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| Feeling Dizzy, Faint, or Lightheaded | General disorders | SAFTEE | Systematic Assessment |
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| Weakness | General disorders | SAFTEE | Systematic Assessment |
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| Trouble Walking | General disorders | SAFTEE | Systematic Assessment |
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| Hair Loss | Skin and subcutaneous tissue disorders | SAFTEE | Systematic Assessment |
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| Confusion or Slowed Thinking | Psychiatric disorders | SAFTEE | Systematic Assessment |
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| Hives | Skin and subcutaneous tissue disorders | SAFTEE | Systematic Assessment |
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| Trouble Breathing | Respiratory, thoracic and mediastinal disorders | SAFTEE | Systematic Assessment |
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| Change in Ability to Taste Food | Gastrointestinal disorders | SAFTEE | Systematic Assessment |
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| Tremors or Shakiness | Nervous system disorders | SAFTEE | Systematic Assessment |
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| Trouble with Gums | General disorders | SAFTEE | Systematic Assessment |
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| Sore Throat | Gastrointestinal disorders | SAFTEE | Systematic Assessment |
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| Unusual Bruising or Bleeding | Skin and subcutaneous tissue disorders | SAFTEE | Systematic Assessment |
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| Double Vision or Changes In Vision | Eye disorders | SAFTEE | Systematic Assessment |
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| Weight Loss | General disorders | SAFTEE | Systematic Assessment |
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| D001519 | Behavior |
| Sulfur Compounds |
| D007555 | Isoxazoles |
| D001393 | Azoles |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| Visit 5 (Week 5) |
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| Visit 7 (Week 9) |
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| Visit 9 (Week 13) |
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| Visit 10 (Week 16) |
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| Visit 4 (Week 3) |
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| Visit 5 (Week 5) |
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| Visit 6 (Week 7) |
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| Visit 7 (Week 9) |
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| Visit 8 (Week 11) |
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| Visit 9 (Week 13) |
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| Visit 10 (Week 16) |
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| Visit 11 (2 Week follow up) |
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| Visit 12 (3 Month follow up) |
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| Visit 10 (Week 16) |
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| Visit 11 (2 Week Follow up) |
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| Visit 12 (3 Month Follow up) |
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| Visit 12 (3 Month follow up) |
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