Clinical trial NCT02082678: Ondansetron for Bipolar Disorder and Alcohol Use Disorders
Official title: Ondansetron for Bipolar Disorder and Alcohol Use Disorders
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Bipolar Disorder
Alcohol Use Disorder
Dual Diagnosis
Keywords: Bipolar Disorder
BPD
Alcohol Use Disorder
Alcohol Abuse
Alcohol Dependence
Ondansetron
Cognition
Mood
Lead sponsor: University of Texas Southwestern Medical Center
Sponsor class: OTHER
Collaborators: name: Stanley Medical Research Institute
First posted: 2014-03-10
Enrollment: 70
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Detailed description: A total of 70 outpatients with alcohol use disorder and BPD, cyclothymic disorder, schizoaffective disorder (bipolar type), or MDD with mixed features will be enrolled in a 12-week, randomized, double-blind, parallel-group, placebo-controlled study of ondansetron. Participant will receive either ondansetron or a placebo for 12 weeks. He or she has an equal chance of receiving ondansetron or placebo.

Randomization will be stratified based on \> 4 or ≤ 4 drinking days per week at start of the study. Ondansetron or placebo will be given at 0.5 milligrams twice a day for the first 4 weeks. At weeks 4, 8 and 10 the dose may be increased to 1.0, 2.0 or 4.0 milligrams twice a day, respectively, if significant reductions in depression and alcohol use are not observed and the participant is not experiencing any side effects. Blood will be drawn for routine laboratory analyses including a complete blood count (CBC), liver panel, and Carbohydrate-deficient Transferrin (CDT) at baseline and weeks 4, 8 and 12.

Each participant will return for weekly follow-up visits and repeat outcome measures. Pill counts will be conducted, and a list of current medications and doses will be recorded at each visit. Participants will be compensated at each appointment with a bus pass, gift cards, and a monetary incentive for compliance. Participants will be evaluated by both the research assistant (RA) and principal investigator (PI) at each visit.

The Hamilton Rating Scale for Depression (HAMD) and Timeline Followback (TLFB) will be given at each visit as the primary outcome measures. Cognitive assessments will be performed at baseline and week 12.

Eligibility criteria: Inclusion Criteria:

* 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

Exclusion Criteria:

* 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)

Primary outcomes:
measure: Hamilton Rating Scale for Depression (HAMD)
timeFrame: Baseline and Week 12
measure: Number of Standard Drinks Per Assessment Period on Timeline Followback (TLFB)
timeFrame: Baseline and Week 12
measure: Number of Heavy Drinking Days Per Assessment Period on Timeline Followback (TLFB)
timeFrame: Baseline and Week 12
Secondary outcomes:
Other outcomes:
Locations:
city: Dallas
country: United States
facility: The University of Texas Southwestern Medical Center
state: Texas
Study officials:
affiliation: UT Southwestern Medical Center
name: E. Sherwood Brown, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: