Aripiprazole for Bipolar Disorder and Alcohol Use Disorder

Sponsor

University of Texas Southwestern Medical Center (Other)

Overall Status

Recruiting

CT.gov ID

NCT02918370

Collaborator

(none)

132

Enrollment

Location

Arms

Anticipated Duration (Months)

1.8

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The investigators will conduct a 12-week, randomized, double-blind, parallel-group, placebo-controlled study of aripiprazole in 132 persons with Alcohol Use Disorder (AUD) and bipolar I or II disorder, currently depressed or mixed phase. Primary Aim will be to assess change in alcohol use by the Timeline Followback (TLFB) method. Secondary Aim will include change in alcohol craving using the Penn Alcohol Craving Scale (PACS). Changes in psychiatric symptoms (mania/hypomania and depression) and predictors of response will be assessed. Participants with ≥ 1 drinking day at week 12 will be enrolled in a 4-week extension phase with an upward titration to 30 mg/day for those in the active treatment group. The placebo group will remain on placebo.

Subjects will be discontinued from the study if any of the following conditions occurs:

change in diagnosis to other than bipolar I or II disorder and AUD, development of active suicidal or homicidal ideation with plan and intent, worsening in mood symptoms, that in the opinion of the investigators requires discontinuation, pregnancy, development of severe or life-threatening medical condition, involuntary psychiatric hospitalization or incarceration, significant alcohol withdrawal (e.g. delirium tremens) based on clinical judgment (increases in Clinical Institute Withdrawal Assessment for Alcohol (CIWA-Ar) scores will initiate a careful clinical assessment of possible worsening of withdrawal symptoms), or cocaine or amphetamine-positive urine drug screen during the study.

Condition or Disease	Intervention/Treatment	Phase
Bipolar Disorder Alcoholism Alcohol Abuse	Drug: Aripiprazole Drug: Placebo	Phase 3

Study Design

Study Type:

Interventional

Anticipated Enrollment :

132 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Triple (Participant, Care Provider, Investigator)

Primary Purpose:

Treatment

Official Title:

Aripiprazole for Bipolar Disorder and Alcohol Use Disorder

Actual Study Start Date :

Nov 1, 2016

Anticipated Primary Completion Date :

Dec 31, 2022

Anticipated Study Completion Date :

Dec 31, 2022

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Aripiprazole Aripiprazole will be given to the participant beginning at 2 mg per day(QD) then titrating up to 5 mg QD at week 1, 10 mg QD at week 2, 15 mg QD at week 3 until the end of the preliminary phase. If the participant qualifies for the extension phase, then they will be titrated up again at week 12 to 30 mg QD.	Drug: Aripiprazole Aripiprazole is an atypical antipsychotic drug that is used to treat mental/mood disorders. It works to restore the balance of neurotransmitters. Other Names: Abilify
Placebo Comparator: Placebo Matching placebo will be given to the participant beginning at 2mg QD then titrating up to 5 mg QD at week 1, 10 mg QD at week 2, 15 mg QD at week 3 until the end of the preliminary phase. If the participant qualifies for the extension phase, then they will be titrated up again at week 12 to 30 mg QD.	Drug: Placebo Inactive ingredient matching the active comparators in appearance. Other Names: Sugar Pill

Arm

Intervention/Treatment

Experimental: Aripiprazole

Aripiprazole will be given to the participant beginning at 2 mg per day(QD) then titrating up to 5 mg QD at week 1, 10 mg QD at week 2, 15 mg QD at week 3 until the end of the preliminary phase. If the participant qualifies for the extension phase, then they will be titrated up again at week 12 to 30 mg QD.

Drug: Aripiprazole

Aripiprazole is an atypical antipsychotic drug that is used to treat mental/mood disorders. It works to restore the balance of neurotransmitters.

Other Names:

Abilify

Placebo Comparator: Placebo

Matching placebo will be given to the participant beginning at 2mg QD then titrating up to 5 mg QD at week 1, 10 mg QD at week 2, 15 mg QD at week 3 until the end of the preliminary phase. If the participant qualifies for the extension phase, then they will be titrated up again at week 12 to 30 mg QD.

Drug: Placebo

Inactive ingredient matching the active comparators in appearance.

Other Names:

Sugar Pill

Outcome Measures

Primary Outcome Measures

Timeline Follow Back (TLFB) [12 weeks]
The Timeline Followback is used to assess recent alcohol use (and if present, other substance use).

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 65 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Outpatient men and women age 18-65 years old with bipolar I, II, Not Otherwise Specified (NOS) disorder, or Schizoaffective Bipolar Type
If diagnosed with Bipolar I, Bipolar NOS w/history of mania or Schizoaffective Disorder Bipolar Type, current mood stabilizer therapy (lithium, valproic acid, lamotrigine, gabapentin) with stable dose for > 28 days prior to randomization.
Baseline Barrett Impulsiveness Scale-11 Score of > 62 (above average impulsivity)
Systolic BP > 100 and < 165 and Diastolic BP > 60 and < 105 with no evidence of orthostatic hypotension
Current Diagnosis of Alcohol Use Disorder with at least moderate severity
Alcohol use of an average of 15 drinks per 7 days in the past 28 days prior to intake for men, and an average of 8 drinks per 7 day period in the past 28 days prior to intake for women
Current mood stabilizer therapy with stable dose for > 28 days
Fluent in English or Spanish

Exclusion Criteria:

Baseline Hamilton Rating Scale for Depression (HRSD) or Young Mania Rating Scale (YMRS) scores > 35
Mood disorders other than bipolar I, II, NOS or schizoaffective disorder bipolar type (e.g. cyclothymic disorders, schizophrenia, schizoaffective disorder depressive type, or unipolar depression based on the SCID), other disorders, e.g. anxiety disorders, will be allowed.
Current diagnosis of amphetamine or cocaine use disorder or a cocaine or amphetamine positive baseline urine sample.
Evidence of clinically significant alcohol withdrawal symptoms
Current treatment with an atypical antipsychotic
Current treatment with naltrexone, acamprosate, disulfiram, or topiramate in the last 28 days
Prior treatment with Aripiprazole within the last year or lifetime history of intolerable side effects to Aripiprazole
Vulnerable populations (e.g. pregnant, nursing, cognitively impaired, incarcerated.)
Evidence of clinically significant alcohol withdrawal symptoms defined as a CIWA-Ar score of ≥ 10.
High risk for suicide
Aspartate Amino Transferase (AST) or Alanine Amino Transferase (ALT) > 3 times upper limit of normal
Current use of Cytochrome P450 3A4 inducing medication (e.g. carbamazepine, rifabutin, rifampin, ritonavir).
Use of other substances (besides cocaine/amphetamine) is allowed if the use disorder is no greater than moderate severity and alcohol is the self-identified substance of choice.
History of neuroleptic malignant syndrome or tardive dyskinesia.