Interdisciplinary Study of A Novel Anticonvulsant in Alcoholism

NCT02901041 | Completed Phase 3 Results DMC FDA Drug

• 1 other identifier: 2R01AA015923-06
• Study Type: interventional
• Target: 81
• Locations: 1 country
• Sites: 1

Brief Summary

Alcoholism is the third leading cause of preventable death in the US, accounting for 80,000 deaths annually. Almost 18 million US adults have alcohol use disorder (AUD); however, approved medications for the treatment of AUD has shown limited effectiveness. Zonisamide (ZON), a broad spectrum anticonvulsant, has proven to be more effective than a placebo in reducing alcohol intake in individuals with alcohol dependence. ZON's mechanism of action seems to be quite distinct from currently approved anti-alcoholism medications, which holds promise for treatment of individuals who are not responsive to conventional medications. However, much remains unknown about ZON's therapeutic mechanisms and ZON's efficacy in treating patients with a diagnosis of AUD. To fill in these gaps, the investigators will conduct a double-blind randomized controlled study that assesses ZON's treatment mechanisms and effectiveness in reducing alcohol consumption in patients with AUD. Participants will be randomized to one of two conditions: 1) treatment with ZON and a computerized psychotherapy platform called Take Control (TC); 2) treatment with a placebo (PLC) and TC. To understand the neurobiology behind ZON's potential therapeutic effects on AUD, fMRI will be used to compare the brain activity of the ZON+TC versus PLC+TC group while participants perform an alcohol and emotional-word Stroop task, as well as an alcohol related cues task.

Conditions

Alcohol Dependence

Outcome Measures

Primary Outcomes (8)

• Average Standard Drinking Units Per Day

  Timeline followback (TLFB) was used to collect information on participant's daily drinking. TLFB is a form of interview used to collect retroactive data related to participant's drinking. Participants are presented with a calendar are asked to report what they drank each day for a specified timeframe (e.g. in the past week). Participants were encouraged to give their best estimate in the absence of total certainty regarding their drinking on a given day. Study assessors then used these responses to identify how many standard drinking units participants drank each day. The National Institute of Alcohol Abuse and Alcoholism (NIAAA) defines "one standard drinking unit" as containing 14 grams of pure alcohol, and provide guidelines for calculating standard drinking units based on the alcohol content and size of a given drink. TLFB data from 28 days before BL were used to calculate pre-treatment outcomes. In instances where 28 days of data were not available, 21 days were used instead.

  Pre-treatment

• Average Standard Drinking Units Per Day

  Timeline followback (TLFB) was used to collect information on participant's daily drinking. TLFB is a form of interview used to collect retroactive data related to participant's drinking. Participants are presented with a calendar are asked to report what they drank each day for a specified timeframe (e.g. in the past week). Participants were encouraged to give their best estimate in the absence of total certainty regarding their drinking on a given day. Study assessors then used these responses to identify how many standard drinking units participants drank each day. The National Institute of Alcohol Abuse and Alcoholism (NIAAA) defines "one standard drinking unit" as containing 14 grams of pure alcohol, and provide guidelines for calculating standard drinking units based on the alcohol content and size of a given drink. TLFB data from 28 days before BL were used to calculate pre-treatment outcomes. In instances where 28 days of data were not available, 21 days were used instead.

  Post-treatment (Week 12)

• Percentage of Drinking Days

  Timeline followback (TLFB) was used to collect information on participant's daily drinking. TLFB is a form of interview used to collect retroactive data related to participant's drinking. Participants are presented with a calendar are asked to report what they drank each day for a specified timeframe (e.g. in the past week). Participants were encouraged to give their best estimate in the absence of total certainty regarding their drinking on a given day. Study assessors then used these responses to identify how many standard drinking units participants drank each day. The National Institute of Alcohol Abuse and Alcoholism (NIAAA) defines "one standard drinking unit" as containing 14 grams of pure alcohol, and provide guidelines for calculating standard drinking units based on the alcohol content and size of a given drink. TLFB data from 28 days before BL were used to calculate pre-treatment outcomes. In instances where 28 days of data were not available, 21 days were used instead.

  Pre-treatment

• Percentage of Drinking Days

  Timeline followback (TLFB) was used to collect information on participant's daily drinking. TLFB is a form of interview used to collect retroactive data related to participant's drinking. Participants are presented with a calendar are asked to report what they drank each day for a specified timeframe (e.g. in the past week). Participants were encouraged to give their best estimate in the absence of total certainty regarding their drinking on a given day. Study assessors then used these responses to identify how many standard drinking units participants drank each day. The National Institute of Alcohol Abuse and Alcoholism (NIAAA) defines "one standard drinking unit" as containing 14 grams of pure alcohol, and provide guidelines for calculating standard drinking units based on the alcohol content and size of a given drink. TLFB data from 28 days before BL were used to calculate pre-treatment outcomes. In instances where 28 days of data were not available, 21 days were used instead.

  Post-treatment (Week 12)

• Percent Heavy Drinking Days

  TLFB was be used to estimate participants' daily drinking. In this assessment, participants are presented with a calendar and asked to provide retrospective estimates of their daily alcohol consumption over a specified time period. TLFB was used to gather information on participants' daily drinking. In this assessment, participants are presented with a calendar and asked to provide retrospective estimates of their daily alcohol consumption over a specified time period. TLFB data from 28 days before BL were used to calculate pre-treatment outcomes. In instances where 28 days of data were not available, 21 days were used instead. Heavy drinking days refers to the percentage of heavy drinking days within that window (4 or more drinks for women, 5 or more for men).

  Pre-treatment

• Percent Heavy Drinking Days

  TLFB was be used to estimate participants' daily drinking. (See outcome measure 1 for more details description.) In this assessment, participants are presented with a calendar and asked to provide retrospective estimates of their daily alcohol consumption over a specified time period. TLFB data from 28 days before post-treatment were used to calculate post-treatment outcomes. In instances where 28 days of data were not available, 21 days were used instead. Heavy drinking days refers to the percentage of heavy drinking days within that window (4 or more drinks for women, 5 or more for men).

  Post-treatment (Week 12)

• Average Weekly Standard Drinking Units (SDUs)

  Timeline follow back is a form of interview used to collect retroactive data related to participant's drinking. Participants are presented with a calendar are asked to report what they drank each day for a specified timeframe (e.g. in the past week). Participants were encouraged to give their best estimate in the absence of total certainty regarding their drinking on a given day. Study assessors then used these responses to identify how many standard drinking units participants drank each day. The National Institute of Alcohol Abuse and Alcoholism (NIAAA) defines "one standard drinking unit" as containing 14 grams of pure alcohol, and provide guidelines for calculating standard drinking units based on the alcohol content and size of a given drink. These standards, which can be found the NIAAA website, were used to calculate participant's average drinking units.

  Pre-treatment

• Average Weekly Standard Drinking Units (SDUs)

  Timeline followback (TLFB) was used to collect information on participant's daily drinking. TLFB is a form of interview used to collect retroactive data related to participant's drinking. Participants are presented with a calendar are asked to report what they drank each day for a specified timeframe (e.g. in the past week). Participants were encouraged to give their best estimate in the absence of total certainty regarding their drinking on a given day. Study assessors then used these responses to identify how many standard drinking units participants drank each day. The National Institute of Alcohol Abuse and Alcoholism (NIAAA) defines "one standard drinking unit" as containing 14 grams of pure alcohol, and provide guidelines for calculating standard drinking units based on the alcohol content and size of a given drink. TLFB data from 28 days before BL were used to calculate pre-treatment outcomes. In instances where 28 days of data were not available, 21 days were used instead.

  Post-treatment (Week 12)

Secondary Outcomes (18)

• Balloon Analogue Risk Task: Total Pump Count

  Pre-treatment

• Balloon Analogue Risk Task: Total Pump Count

  Post-treatment (Week 12)

• Cued Go/No-go Task: Inhibition Error

  Pre-treatment

• Cued Go No-Go: Inhibition Error

  Post-treatment (Week 12)

• Connor's Continuous Performance Task (CPT) - X Test Omission Rate

  Pre-treatment

Study Arms (2)

Zonisamide & Computerized Psychotherapy

EXPERIMENTAL

Zonisamide capsules (with a target maintenance dose of 400 mg daily) and a seven module computerized psychotherapy for alcohol use disorders called Take Control (9 sessions) will be administered over the course of 12 weeks, followed by a two week medication taper.

Drug: Zonisamide; Behavioral: Take Control

Placebo & Computerized Psychotherapy

ACTIVE COMPARATOR

Placebo capsules (for zonisamide) and a seven module computerized psychotherapy for alcohol use disorders called Take Control will be administered over the course of 14 weeks.

Behavioral: Take Control; Drug: Placebo (for Zonisamide)

Interventions

Zonisamide DRUG

ZONEGRAN® (zonisamide) is an antiseizure drug chemically classified as a sulfonamide and unrelated to other antiseizure agents. A dose of 400 mg daily will be used as the target maintenance dose in this study but dosing will be modified if needed to adjust for subject tolerance of drug dosing.

Also known as: Zonegran

Zonisamide & Computerized Psychotherapy

Take Control BEHAVIORAL

Take Control is a seven module computer-based intervention which presents evidence-based alcohol education that includes motivational interviewing and cognitive-behavioral skills building. This program is derived from the National Institute on Alcohol Abuse and Alcoholism's (NIAAA's) self-help approach, Rethinking Drinking. Starting on March 23, 2020, participants will participate in a simplified Take Control treatment at home due to the COVID-19 pandemic

Placebo & Computerized Psychotherapy; Zonisamide & Computerized Psychotherapy

Placebo (for Zonisamide) DRUG

Sugar pills manufactured to mimic Zonisamide capsules.

Placebo & Computerized Psychotherapy

Eligibility Criteria

• Age: 21 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• DSM-5 diagnosis of an Alcohol Use Disorder (AUD)
• Adults ages 21 to 65 years old
• Expressed desire to stop drinking alcohol completely or to reduce alcohol consumption
• Reported drinking an average of at least 14 standard drinks per week for males, or 7 for females occurring over a 28-consecutive day period during the 90 day-long time window that preceded the screening session
• Must be willing to discontinue psychotherapy for substance use disorder (except A.A.)

You may not qualify if:

• Bipolar disorder, schizophrenia, current bulimia/anorexia, dementia, or other substance use disorder, with the exception of nicotine, marijuana, and caffeine
• Clear and current suicidal risk
• Significant medical problem (e.g. uncontrolled diabetes)
• Medical contraindication to the use of ZON (e.g. history of significant renal disease, kidney stones, liver problems, metabolic acidosis, etc), as indicated by the FDA Zonisamide medication guide
• History of anticonvulsant-induced rash
• Currently taking:
• acamprosate, naltrexone, topiramate, disulfiram, or benzodiazepines
• a medication that is a moderate or major inhibitor or inducer of cytochrome P450 3A4 enzymes
• an amphetamine or other psychomotor stimulant
• opioids or have been treated chronically with opioids
• antipsychotic agents, anticonvulsants, or sedative hypnotics
• drugs with "sulfa" moiety (e.g. sulfonamides, sulfonylureas, carbonic anhydrase inhibitors, thiazides, and loop diuretics), except ethacrynic acid
• anxiolytics or antidepressants
• Previously received ZON for the treatment of an AUD
• Known allergy to sulfonamides

Sponsors & Collaborators

• Boston University Charles River Campus: lead
• Mclean Hospital: collaborator
• University of Houston: collaborator

Study Sites (1)

Center for Anxiety and Related Disorders - Boston University

Boston, Massachusetts, 02115, United States

Location

MeSH Terms

Conditions

Alcoholism

Interventions

Zonisamide

Condition Hierarchy (Ancestors)

Alcohol-Related Disorders; Substance-Related Disorders; Chemically-Induced Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Sulfonamides; Amides; Organic Chemicals; Sulfones; Sulfur Compounds; Isoxazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Dr. Todd Farchione
• Organization: Boston University

tfarchio@bu.edu

(617) 353-9610

Study Officials

• David H Barlow, PhD

  Boston University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Research Associate Professor

Study Record Dates

• First Submitted: August 29, 2016
• First Posted: September 15, 2016
• Study Start: September 21, 2017
• Primary Completion: January 4, 2022
• Study Completion: January 4, 2022
• Last Updated: June 18, 2023
• Results First Posted: May 6, 2023

Record last verified: 2023-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)