Ondansetron for Bipolar Disorder and Alcohol Use Disorders

NCT02082678 | Completed Phase 4 Results DMC

• 1 other identifier: 112013-075
• Study Type: interventional
• Target: 70
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of the study is to determine if ondansetron, as an add-on therapy, is associated with reduced depressive symptoms and alcohol use in outpatients with bipolar disorder (BPD), cyclothymic disorder, schizoaffective disorder (bipolar type) and major depressive disorder (MDD) with mixed features. The investigators will also use blood samples to determine if the genotype for the serotonin transporter gene is associated with response to ondansetron.

Conditions

Bipolar Disorder; Alcohol Use Disorder; Dual Diagnosis

Keywords

Bipolar Disorder; BPD; Alcohol Use Disorder; Alcohol Abuse; Alcohol Dependence; Ondansetron; Cognition; Mood

Outcome Measures

Primary Outcomes (3)

• Hamilton Rating Scale for Depression (HAMD)

  The Hamilton Rating Scale for Depression (HAMD) is a 17-item observer-rated measure of depressive symptomatology. HAMD is scored between 0 and 4 points, with the total score ranging from 0 to 52. Scoring is based on the 17-item scale and scores of 0-7 are considered as being normal, 8-16 suggest mild depression, 17-23 moderate depression and scores over 24 are indicative of severe depression. The higher scores are associated with greater depressive symptom severity and poorer outcome.

  Baseline and Week 12

• Number of Standard Drinks Per Assessment Period on Timeline Followback (TLFB)

  The Timeline Followback (TLFB) will be used to assess the change in the number of standard alcoholic drinks per week. The TLFB is interviewer-administered and asks participants to retrospectively estimate their alcohol use between each visit. The reported drinks are then converted to standard drinks based on the drink's alcohol by volume (ABV). The higher number is associated with more standard drinks and worse outcome. Values are corrected for the number of days covered in the assessment period.

  Baseline and Week 12

• Number of Heavy Drinking Days Per Assessment Period on Timeline Followback (TLFB)

  The Timeline Followback (TLFB) will be used to assess the change in the number of standard alcoholic drinks per week. The TLFB involves asking participants to retrospectively estimate their alcohol between each research visit. The reported drinks are then converted to heavy drinking days based on the drink's alcohol by volume (ABV) and participant's sex (male/female) - 5 drinks per day for males and 4 for females. Each day during which 4-5 drinks are consumed is counted as a heavy drinking day within a given assessment period. The reported values are corrected for days covered (divided by the number of days between each visit). The higher number is associated with more heavy drinking days and worse outcome.

  Baseline and Week 12

Study Arms (2)

Ondansetron

ACTIVE COMPARATOR

Ondansetron will be given 0.5 mg twice a day (BID). The dose may be increased from 0.5 mg/BID to 1.0 mg/BID at week 4 for participants with less than 30% reduction in HAMD and/or alcohol use. An additional dose increase to 2.0 mg/BID and 4.0 mg/BID is allowed at weeks 8 and 10, respectively, for participants with less than a 50% reduction in HAMD scores and/or alcohol use.

Drug: Ondansetron

Placebo

PLACEBO COMPARATOR

Placebo will be given 0.5 mg/ BID. The dose may be increased from 0.5 mg/BID to 1.0 mg/BID at week 4 for participants with less than 30% reduction in HAMD and/or alcohol use. An additional dose increase to 2.0 mg/BID and 4.0 mg/BID is allowed at weeks 8 and 10, respectively, for participants with less than a 50% reduction in HAMD scores and/or alcohol use.

Drug: Placebo

Interventions

Ondansetron DRUG

Ondansetron is a serotonin receptor antagonist that is FDA-approved to treat nausea and vomiting caused by cancer therapy and surgery.

Also known as: Zofran, Zuplenz

Ondansetron

Placebo DRUG

Inactive ingredient matching the active medication in appearance

Also known as: Sugar-pill

Placebo

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Outpatient men and women age 18-70 years old with bipolar I, II, or Not Otherwise Specified (NOS) disorders, schizoaffective disorder (bipolar type), cyclothymic disorder, or major depressive disorder with mixed features
• Current diagnosis of alcohol use disorder (DSM V terminology) with onset ≤ age 25
• Alcohol use (by self-report) of at least 15 drinks in the 7 days prior to intake
• IF diagnosis of Bipolar I, II, or NOS Disorder: Current mood stabilizer therapy (lithium, anticonvulsant, atypical antipsychotic) with stable dose for at least 14 days prior to randomization
• IF diagnosis of Schizoaffective disorder (bipolar type): Current atypical antipsychotic therapy with stable dose for at least 14 days prior to randomization
• IF diagnosis of Major Depressive Disorder with mixed features: Current antidepressant therapy with stable dose for at least 14 days prior to randomization

You may not qualify if:

• Baseline Young Mania Rating Scale (YMRS) or Hamilton Rating Scale for Depression (HAMD) scores ≥ 35 to exclude those with very severe mood symptoms
• Evidence of clinically significant alcohol withdrawal symptoms defined as a CIWA-Ar (Clinical Institute Withdrawal Assessment of Alcohol Use-Revised) score of ≥ 10
• Therapy in past 14 days with naltrexone, acamprosate, disulfiram, or topiramate
• Vulnerable populations (e.g. pregnant, breastfeeding, incarcerated, cognitively impaired (e.g. dementia, mentally challenged))
• High risk of suicide defined as \> 1 attempt in past 12 months that required medical attention, any attempt in the past 3 months or current suicidal ideation with plan and intent such that outpatient care is precluded
• Intensive outpatient treatment (defined as ≥ 3 visits each week) for substance abuse (AA, NA meetings, or less intensive counseling at baseline will be allowed)
• Severe or life-threatening medical condition (e.g., hepatic cirrhosis) or laboratory or physical examination findings consistent with serious medical illness (e.g., dangerously abnormal electrolytes)
• AST (aspartate aminotransferase ) or ALT (alanine transaminase) \> 3 times the upper limit of normal
• History of severe side effects or allergic reaction with prior ondansetron therapy (e.g. for vomiting) or use of medications with significant drug-drug interactions with ondansetron (phenytoin, carbamazepine, and rifampicin, apomorphine, tramadol)

Sponsors & Collaborators

• University of Texas Southwestern Medical Center: lead
• Stanley Medical Research Institute: collaborator

Study Sites (1)

The University of Texas Southwestern Medical Center

Dallas, Texas, 75390, United States

Location

MeSH Terms

Conditions

Bipolar Disorder; Alcoholism

Interventions

Ondansetron

Condition Hierarchy (Ancestors)

Bipolar and Related Disorders; Mood Disorders; Mental Disorders; Alcohol-Related Disorders; Substance-Related Disorders; Chemically-Induced Disorders

Intervention Hierarchy (Ancestors)

Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Carbazoles; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds, 3-Ring

Results Point of Contact

• Title: E. Sherwood Brown. MD, PhD, MBA
• Organization: UT Southwestern

Sherwood.Brown@UTSouthwestern.edu

(214) 645-6950

Study Officials

• E. Sherwood Brown, MD, PhD

  University of Texas Southwestern Medical Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: PROFESSOR

Study Record Dates

• First Submitted: March 6, 2014
• First Posted: March 10, 2014
• Study Start: February 1, 2014
• Primary Completion: May 1, 2018
• Study Completion: May 1, 2018
• Last Updated: August 24, 2021
• Results First Posted: July 20, 2020

Record last verified: 2021-08

Locations

US (1)