Trial Outcomes & Findings for Ondansetron for Bipolar Disorder and Alcohol Use Disorders (NCT NCT02082678)

NCT ID: NCT02082678

Last Updated: 2021-08-24

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

70 participants

Primary outcome timeframe

Baseline and Week 12

Results posted on

2021-08-24

Participant Flow

Participant milestones

Participant milestones
Measure	Ondansetron Ondansetron will be given at the dose of 0.5 mg twice a day. The dose may be increased from 0.5 mg twice a day to 1.0 mg twice a day at week 4 for participants with less than 30% reduction in the Hamilton Depression Rating Scale (HAMD) and/or alcohol use based on Timeline Followback (TLFB) assessment of alcohol use. An additional dose increase to 2.0 mg twice a day and 4.0 mg twice a day is allowed at weeks 8 and 10, respectively, for participants with less than a 50% reduction in HAMD scores and/or TLFB.	Placebo Placebo that matches the active medication in appearance will be started at 0.5 mg capsule twice day. The dose may be increased from 0.5 mg twice day to 1.0 mg twice a day at week 4 for participants with less than 30% reduction in the Hamilton Depression Rating Scale (HAMD) and/or alcohol use per Timeline Followback (TLFB) assessment score. An additional dose increase to 2.0 mg twice a day and 4.0 mg twice a day is allowed at weeks 8 and 10, respectively, for participants with less than a 50% reduction in HAMD scores and/or alcohol use per TLFB.
Overall Study STARTED	35	35
Overall Study COMPLETED	23	21
Overall Study NOT COMPLETED	12	14

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Ondansetron for Bipolar Disorder and Alcohol Use Disorders

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Ondansetron n=35 Participants Ondansetron 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. Ondansetron: Ondansetron is a serotonin receptor antagonist that is FDA-approved to treat nausea and vomiting caused by cancer therapy and surgery.	Placebo n=35 Participants 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. Placebo: Inactive ingredient matching the active medication in appearance	Total n=70 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants
Age, Categorical Between 18 and 65 years	35 Participants n=99 Participants	35 Participants n=107 Participants	70 Participants n=206 Participants
Age, Categorical >=65 years	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants
Sex: Female, Male Female	11 Participants n=99 Participants	17 Participants n=107 Participants	28 Participants n=206 Participants
Sex: Female, Male Male	24 Participants n=99 Participants	18 Participants n=107 Participants	42 Participants n=206 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=99 Participants	1 Participants n=107 Participants	1 Participants n=206 Participants
Race (NIH/OMB) Asian	3 Participants n=99 Participants	3 Participants n=107 Participants	6 Participants n=206 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants
Race (NIH/OMB) Black or African American	18 Participants n=99 Participants	18 Participants n=107 Participants	36 Participants n=206 Participants
Race (NIH/OMB) White	14 Participants n=99 Participants	13 Participants n=107 Participants	27 Participants n=206 Participants
Race (NIH/OMB) More than one race	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants
Age, Continuous	46.54 years STANDARD_DEVIATION 8.60 • n=99 Participants	43.29 years STANDARD_DEVIATION 10.01 • n=107 Participants	44.91429 years STANDARD_DEVIATION 9.41128 • n=206 Participants

PRIMARY outcome

Timeframe: Baseline and Week 12

Population: 11 participants from Ondansetron group and 13 from the Placebo group did not complete this study.

Outcome measures

Outcome measures
Measure	Ondansetron n=35 Participants Ondansetron 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. Ondansetron: Ondansetron is a serotonin receptor antagonist that is FDA-approved to treat nausea and vomiting caused by cancer therapy and surgery.	Placebo n=35 Participants 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. Placebo: Inactive ingredient matching the active medication in appearance
Hamilton Rating Scale for Depression (HAMD) Baseline	13.77 score on a scale Standard Deviation 5.39	14.23 score on a scale Standard Deviation 7.25
Hamilton Rating Scale for Depression (HAMD) Week 12	8.52 score on a scale Standard Deviation 6.02	8.86 score on a scale Standard Deviation 5.77

PRIMARY outcome

Timeframe: Baseline and Week 12

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.

Outcome measures

Outcome measures
Measure	Ondansetron n=35 Participants Ondansetron 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. Ondansetron: Ondansetron is a serotonin receptor antagonist that is FDA-approved to treat nausea and vomiting caused by cancer therapy and surgery.	Placebo n=35 Participants 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. Placebo: Inactive ingredient matching the active medication in appearance
Number of Standard Drinks Per Assessment Period on Timeline Followback (TLFB) Baseline	4.06 mean number of standard drinks per week Standard Deviation 4.07	4.92 mean number of standard drinks per week Standard Deviation 4.09
Number of Standard Drinks Per Assessment Period on Timeline Followback (TLFB) Week 12	2.50 mean number of standard drinks per week Standard Deviation 3.73	2.92 mean number of standard drinks per week Standard Deviation 2.68

PRIMARY outcome

Timeframe: Baseline and Week 12

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.

Outcome measures

Outcome measures
Measure	Ondansetron n=35 Participants Ondansetron 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. Ondansetron: Ondansetron is a serotonin receptor antagonist that is FDA-approved to treat nausea and vomiting caused by cancer therapy and surgery.	Placebo n=35 Participants 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. Placebo: Inactive ingredient matching the active medication in appearance
Number of Heavy Drinking Days Per Assessment Period on Timeline Followback (TLFB) Baseline	0.34 heavy drinking days (corrected) Standard Deviation 0.33	0.45 heavy drinking days (corrected) Standard Deviation 0.37
Number of Heavy Drinking Days Per Assessment Period on Timeline Followback (TLFB) Week 12	0.17 heavy drinking days (corrected) Standard Deviation 0.28	0.20 heavy drinking days (corrected) Standard Deviation 0.28

Adverse Events

Ondansetron

Serious events: 10 serious events

Other events: 7 other events

Deaths: 1 deaths

Placebo

Serious events: 4 serious events

Other events: 4 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

E. Sherwood Brown. MD, PhD, MBA

UT Southwestern

Phone: (214) 645-6950

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	Ondansetron n=35 participants at risk Ondansetron 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. Ondansetron: Ondansetron is a serotonin receptor antagonist that is FDA-approved to treat nausea and vomiting caused by cancer therapy and surgery.	Placebo n=35 participants at risk 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. Placebo: Inactive ingredient matching the active medication in appearance
Infections and infestations UTI	2.9% 1/35 • Number of events 1 • 12 weeks Adverse events were assessed by a weekly questionnaire at each appointment.	0.00% 0/35 • 12 weeks Adverse events were assessed by a weekly questionnaire at each appointment.
Infections and infestations Bacterial parasite in gut	2.9% 1/35 • Number of events 1 • 12 weeks Adverse events were assessed by a weekly questionnaire at each appointment.	0.00% 0/35 • 12 weeks Adverse events were assessed by a weekly questionnaire at each appointment.
Blood and lymphatic system disorders Leg swelling	2.9% 1/35 • Number of events 1 • 12 weeks Adverse events were assessed by a weekly questionnaire at each appointment.	0.00% 0/35 • 12 weeks Adverse events were assessed by a weekly questionnaire at each appointment.
Infections and infestations Sepsis	2.9% 1/35 • Number of events 1 • 12 weeks Adverse events were assessed by a weekly questionnaire at each appointment.	0.00% 0/35 • 12 weeks Adverse events were assessed by a weekly questionnaire at each appointment.
Social circumstances Detoxification	2.9% 1/35 • Number of events 1 • 12 weeks Adverse events were assessed by a weekly questionnaire at each appointment.	0.00% 0/35 • 12 weeks Adverse events were assessed by a weekly questionnaire at each appointment.
Social circumstances Suicide attempt	2.9% 1/35 • Number of events 1 • 12 weeks Adverse events were assessed by a weekly questionnaire at each appointment.	2.9% 1/35 • Number of events 1 • 12 weeks Adverse events were assessed by a weekly questionnaire at each appointment.
Psychiatric disorders Manic episode	2.9% 1/35 • Number of events 1 • 12 weeks Adverse events were assessed by a weekly questionnaire at each appointment.	0.00% 0/35 • 12 weeks Adverse events were assessed by a weekly questionnaire at each appointment.
Metabolism and nutrition disorders Hyperglycemia	2.9% 1/35 • Number of events 1 • 12 weeks Adverse events were assessed by a weekly questionnaire at each appointment.	5.7% 2/35 • Number of events 2 • 12 weeks Adverse events were assessed by a weekly questionnaire at each appointment.
Infections and infestations Corneal ulcer	2.9% 1/35 • Number of events 1 • 12 weeks Adverse events were assessed by a weekly questionnaire at each appointment.	0.00% 0/35 • 12 weeks Adverse events were assessed by a weekly questionnaire at each appointment.
Nervous system disorders Spinal disk degeneration	2.9% 1/35 • Number of events 1 • 12 weeks Adverse events were assessed by a weekly questionnaire at each appointment.	0.00% 0/35 • 12 weeks Adverse events were assessed by a weekly questionnaire at each appointment.
Infections and infestations Cellulitis	0.00% 0/35 • 12 weeks Adverse events were assessed by a weekly questionnaire at each appointment.	2.9% 1/35 • Number of events 1 • 12 weeks Adverse events were assessed by a weekly questionnaire at each appointment.
General disorders Death	2.9% 1/35 • Number of events 1 • 12 weeks Adverse events were assessed by a weekly questionnaire at each appointment.	0.00% 0/35 • 12 weeks Adverse events were assessed by a weekly questionnaire at each appointment.
Social circumstances Suicide ideation	2.9% 1/35 • Number of events 1 • 12 weeks Adverse events were assessed by a weekly questionnaire at each appointment.	2.9% 1/35 • Number of events 1 • 12 weeks Adverse events were assessed by a weekly questionnaire at each appointment.
Cardiac disorders Prolonged QTc interval	2.9% 1/35 • Number of events 1 • 12 weeks Adverse events were assessed by a weekly questionnaire at each appointment.	0.00% 0/35 • 12 weeks Adverse events were assessed by a weekly questionnaire at each appointment.
Cardiac disorders Hypertension	2.9% 1/35 • Number of events 1 • 12 weeks Adverse events were assessed by a weekly questionnaire at each appointment.	0.00% 0/35 • 12 weeks Adverse events were assessed by a weekly questionnaire at each appointment.

Measure	Ondansetron n=35 participants at risk Ondansetron 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. Ondansetron: Ondansetron is a serotonin receptor antagonist that is FDA-approved to treat nausea and vomiting caused by cancer therapy and surgery.	Placebo n=35 participants at risk 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. Placebo: Inactive ingredient matching the active medication in appearance
Skin and subcutaneous tissue disorders Rash	2.9% 1/35 • Number of events 1 • 12 weeks Adverse events were assessed by a weekly questionnaire at each appointment.	0.00% 0/35 • 12 weeks Adverse events were assessed by a weekly questionnaire at each appointment.
Gastrointestinal disorders Indigestion	2.9% 1/35 • Number of events 1 • 12 weeks Adverse events were assessed by a weekly questionnaire at each appointment.	0.00% 0/35 • 12 weeks Adverse events were assessed by a weekly questionnaire at each appointment.
General disorders Hot flashes	2.9% 1/35 • Number of events 1 • 12 weeks Adverse events were assessed by a weekly questionnaire at each appointment.	0.00% 0/35 • 12 weeks Adverse events were assessed by a weekly questionnaire at each appointment.
Gastrointestinal disorders GERD	2.9% 1/35 • Number of events 1 • 12 weeks Adverse events were assessed by a weekly questionnaire at each appointment.	0.00% 0/35 • 12 weeks Adverse events were assessed by a weekly questionnaire at each appointment.
Injury, poisoning and procedural complications Pain in finger and foot	0.00% 0/35 • 12 weeks Adverse events were assessed by a weekly questionnaire at each appointment.	2.9% 1/35 • Number of events 1 • 12 weeks Adverse events were assessed by a weekly questionnaire at each appointment.
General disorders Drowsiness	0.00% 0/35 • 12 weeks Adverse events were assessed by a weekly questionnaire at each appointment.	2.9% 1/35 • Number of events 1 • 12 weeks Adverse events were assessed by a weekly questionnaire at each appointment.
General disorders Headache	0.00% 0/35 • 12 weeks Adverse events were assessed by a weekly questionnaire at each appointment.	2.9% 1/35 • Number of events 1 • 12 weeks Adverse events were assessed by a weekly questionnaire at each appointment.
General disorders Sedation	0.00% 0/35 • 12 weeks Adverse events were assessed by a weekly questionnaire at each appointment.	2.9% 1/35 • Number of events 1 • 12 weeks Adverse events were assessed by a weekly questionnaire at each appointment.
Psychiatric disorders Auditory hallucinations	0.00% 0/35 • 12 weeks Adverse events were assessed by a weekly questionnaire at each appointment.	5.7% 2/35 • Number of events 2 • 12 weeks Adverse events were assessed by a weekly questionnaire at each appointment.
General disorders Swollen feet	2.9% 1/35 • Number of events 1 • 12 weeks Adverse events were assessed by a weekly questionnaire at each appointment.	2.9% 1/35 • Number of events 1 • 12 weeks Adverse events were assessed by a weekly questionnaire at each appointment.
General disorders Dehydration	0.00% 0/35 • 12 weeks Adverse events were assessed by a weekly questionnaire at each appointment.	2.9% 1/35 • Number of events 1 • 12 weeks Adverse events were assessed by a weekly questionnaire at each appointment.
Gastrointestinal disorders Nausea	2.9% 1/35 • Number of events 1 • 12 weeks Adverse events were assessed by a weekly questionnaire at each appointment.	0.00% 0/35 • 12 weeks Adverse events were assessed by a weekly questionnaire at each appointment.
Gastrointestinal disorders Cramping	2.9% 1/35 • Number of events 1 • 12 weeks Adverse events were assessed by a weekly questionnaire at each appointment.	0.00% 0/35 • 12 weeks Adverse events were assessed by a weekly questionnaire at each appointment.
Cardiac disorders Hypertension	2.9% 1/35 • Number of events 1 • 12 weeks Adverse events were assessed by a weekly questionnaire at each appointment.	0.00% 0/35 • 12 weeks Adverse events were assessed by a weekly questionnaire at each appointment.
Eye disorders Glaucoma	2.9% 1/35 • Number of events 1 • 12 weeks Adverse events were assessed by a weekly questionnaire at each appointment.	0.00% 0/35 • 12 weeks Adverse events were assessed by a weekly questionnaire at each appointment.
Social circumstances Suicidal ideation	2.9% 1/35 • Number of events 1 • 12 weeks Adverse events were assessed by a weekly questionnaire at each appointment.	2.9% 1/35 • Number of events 1 • 12 weeks Adverse events were assessed by a weekly questionnaire at each appointment.