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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Aripiprazole | Experimental | 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. |
|
| Placebo | Placebo Comparator | 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. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Aripiprazole | Drug | Aripiprazole is an atypical antipsychotic drug that is used to treat mental/mood disorders. It works to restore the balance of neurotransmitters. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Timeline Follow Back (TLFB) | The Timeline Followback (TLFB) is used to assess recent alcohol use (and if present, other substance use). The calculation is based on the change between baseline and week 12. | 12 weeks |
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Inclusion Criteria:
Exclusion Criteria:
More specific inclusion and exclusion criteria will be discussed with participant at baseline assessment.
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| UT Southwestern | Dallas | Texas | 75235 | United States |
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| ID | Title | Description |
|---|---|---|
| FG000 | 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. Aripiprazole: Aripiprazole is an atypical antipsychotic drug that is used to treat mental/mood disorders. It works to restore the balance of neurotransmitters. |
| FG001 | 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. Placebo: Inactive ingredient matching the active comparators in appearance. |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | 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. Aripiprazole: Aripiprazole is an atypical antipsychotic drug that is used to treat mental/mood disorders. It works to restore the balance of neurotransmitters. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Timeline Follow Back (TLFB) | The Timeline Followback (TLFB) is used to assess recent alcohol use (and if present, other substance use). The calculation is based on the change between baseline and week 12. | Posted | Mean | Standard Deviation | drinks per drinking day | 12 weeks |
|
12 weeks
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | 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. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| increased glucose | Metabolism and nutrition disorders | Non-systematic Assessment | A participant receiving a placebo was hospitalized with high glucose levels. The diagnosis was that pre-diabetes may have progressed to diabetes. Follow-up for further assessment was arranged after discharge. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Restlessness/Fidgeting | General disorders | Non-systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| E. Sherwood Brown MD PhD MBA | UT Southwestern | 214-645-6950 | sherwood.brown@utsouthwestern.edu |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | May 19, 2023 | Jul 30, 2024 | Prot_SAP_000.pdf |
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| ID | Term |
|---|---|
| D001714 | Bipolar Disorder |
| D000437 | Alcoholism |
| D011618 | Psychotic Disorders |
| ID | Term |
|---|---|
| D000068105 | Bipolar and Related Disorders |
| D019964 | Mood Disorders |
| D001523 | Mental Disorders |
| D019973 | Alcohol-Related Disorders |
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| ID | Term |
|---|---|
| D000068180 | Aripiprazole |
| D000073893 | Sugars |
| ID | Term |
|---|---|
| D010879 | Piperazines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D015363 | Quinolones |
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|
| Placebo | Drug | Inactive ingredient matching the active comparators in appearance. |
|
|
| BG001 | 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. Placebo: Inactive ingredient matching the active comparators in appearance. |
| BG002 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| TLFB (Drinks per Drinking Day) | Mean | Standard Deviation | standard drinks per drinking day |
|
| HRSD | The Hamilton Depression Rating Scale is an observer-rated measure of depressive symptomatology. The individual item scores range from 0-4, 0-3 or 0-2 depending on the question. The higher the score represents greater depressive symptom severity. The possible range of scores is 0-52. | Mean | Standard Deviation | units on a scale |
|
| IDS-SR | The Inventory of Depressive Symptoms Self Report (IDS-SR) is a 30-item self-report scale of depressive symptoms. Th scores on each item range from 0-3. Higher scores indicate greater depressive symptom severity. The possible range of scores is 0-84. | Mean | Standard Deviation | units on a scale |
|
| YMRS | The Young Mania Rating Scale (YMRS) is an 11-item, observer-rated measure of manic symptoms. There are four items that are graded on a 0 to 8 scale (irritability, speech, thought content, and disruptive/aggressive behavior), while the remaining seven items are graded on a 0 to 4 scale. These four items are given twice the weight of the others to compensate for poor cooperation from severely ill patients. There are well described anchor points for each grade of severity. The higher score represents a higher level of mania. The possible range of scores is 0-60. | Mean | Standard Deviation | units on a scale |
|
| CIWA-Ar | The Clinical Institute of Withdrawal Assessment of Alcohol (CIWA-Ar) scale is a 10-item, clinician-rated scale of alcohol withdrawal symptoms. Each item scores range from 0-7. Higher scores indicate greater withdrawal symptom severity. The possible range of scores is 0-67. | Mean | Standard Deviation | units on a scale |
|
| PACS | The Penn Alcohol Craving Scale (PACS) is a 5-item questionnaire that measures an individual's craving to drink alcohol in the past week. Each item scores range from 0-6. Higher scores indicate greater craving. The possible range of scores is 0-30. | Mean | Standard Deviation | units on a scale |
|
| BIS-11 | The Barratt Impulsiveness Scale (BIS-11) is a 30 question self-report measure of impulsiveness. It is rated on a four-point Likert scale of 1 = Rarely/Never to 4 = Almost Always/Always. The total scores can range from 30 to 120. Higher scores reflect higher levels of impulsiveness. The possible range of scores is 30-120. | Mean | Standard Deviation | units on a scale |
|
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. Placebo: Inactive ingredient matching the active comparators in appearance. |
|
|
| 0 |
| 36 |
| 0 |
| 36 |
| 13 |
| 36 |
| EG001 | 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. | 0 | 39 | 2 | 39 | 5 | 39 |
|
| Flare up of multiple sclerosis | Nervous system disorders | Non-systematic Assessment | Participant receiving placebo had a flare up of multiple sclerosis requiring hospitalization. |
|
| Increased urinary frequency or difficulty | Renal and urinary disorders | Non-systematic Assessment |
|
| Dry mouth | General disorders | Non-systematic Assessment |
|
| Headache | Nervous system disorders | Non-systematic Assessment |
|
| Nausea or vomiting | Gastrointestinal disorders | Non-systematic Assessment |
|
| erectile dysfunction or decreased libido | General disorders | Non-systematic Assessment |
|
| increased appetite or weight gain | General disorders | Non-systematic Assessment |
|
| Somnolence | General disorders | Non-systematic Assessment |
|
| Insomnia | General disorders | Non-systematic Assessment |
|
| diarrhea | Gastrointestinal disorders | Non-systematic Assessment |
|
| fatigue | General disorders | Non-systematic Assessment |
|
| dyspepsia | Gastrointestinal disorders | Non-systematic Assessment |
|
| constipation | Gastrointestinal disorders | Non-systematic Assessment |
|
| tremors | Nervous system disorders | Non-systematic Assessment |
|
| dizziness or lightheadedness | Nervous system disorders | Non-systematic Assessment |
|
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| D019966 | Substance-Related Disorders |
| D064419 | Chemically-Induced Disorders |
| D019967 | Schizophrenia Spectrum and Other Psychotic Disorders |
| D011804 |
| Quinolines |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D002241 | Carbohydrates |