Enhancing the Effects of Adolescent Alcohol Treatment With Atomoxetine

Study Overview
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Brief Summary
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The primary objectives of this study are twofold. The first primary objective is to evaluate the feasibility, acceptability, and tolerability of atomoxetine (40 mg/day for 3 days then 80 mg/day thereafter) as compared to placebo for 6 weeks plus a psychosocial platform comprised of motivational enhancement therapy and cognitive behavioral therapy (MET-CBT) among adolescents (ages 14 to 19 years) with alcohol use disorder as confirmed by the Diagnostic and Statistical Manual of Mental Disorders - Fifth Edition (DSM-5™). The second primary objective is to leverage a human laboratory paradigm and ecological momentary assessment (EMA) methods to evaluate the effects of atomoxetine on intermediate phenotypes associated with alcohol use and outcomes in clinical trials.

Detailed Description
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This proof-of-concept study is a double-blind, randomized, placebo-controlled, parallel-group, single-site study designed to assess the feasibility, acceptability, and tolerability of atomoxetine for alcohol use disorder among adolescents ages 14 to 19 years. In addition, this project will test the effects of atomoxetine, as compared with placebo, on responses to in vivo alcohol cue exposure in the human laboratory setting. After obtaining consent/parent permission/assent, youth and, if younger than 18 years, their parent will complete a medical history interview to screen for eligibility. Youth will also be screened for eligibility. If eligible for the study, participants will be randomized in an approximate 1:1 ratio (targeting 21 participants per group - 42 participants total) to either atomoxetine or placebo for 6 weeks. Atomoxetine will be dosed at 40 mg/day for three days then increased to the maintenance dose of 80 mg (active) taken orally once daily (QD) for an additional 5.5 weeks. Participants randomized to the placebo condition will be given an equal number of visually matched capsules. Participants will be seen in the clinic at the in-person screening appointment, the randomization/baseline session, and at 8 other times during the study. Three follow-up telephone interviews will occur at 2 weeks and three and six months after the last in-clinic visit. At the randomization/baseline visit and after 4 weeks of investigational product administration (i.e., Study Week 7), participants will undergo a human laboratory paradigm (i.e., alcohol cue reactivity assessment). In addition, participants will complete EMA on a smartphone throughout the day in their daily lives.

Official Title
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Enhancing the Effects of Adolescent Alcohol Treatment With Atomoxetine

Conditions
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Alcohol Use Disorder

Intervention / Treatment
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* Drug: Atomoxetine
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Ages 14 to 20 years, inclusive Self-reports consuming alcohol ≥ 2 days/week on average in the past 28 days Meets the DSM-5 criteria for alcohol use disorder (AUD) Interested in reducing alcohol use Be able to verbalize an understanding of the consent/assent form, able to provide written informed consent/assent, verbalize willingness to complete study procedures, able to understand written and oral instructions in English, and able to complete the questionnaires required by the protocol. If younger than 18 years, parent permissions is required. Be able to take oral medication and be willing to adhere to the medication regimen Complete all assessments required at screening and baseline Provide contact information of someone, such as a parent or other family member, who may be able to contact the subject in case of a missed clinic appointment or follow-up assessment. Be someone who in the opinion of the investigator would be expected to complete the study protocol Agree to the schedule of visits, verbally acknowledge that s/he will be able to attend each scheduled visit, participate in phone visits and that s/he does not have any already scheduled events or a job that may substantially interfere with study participation. Not anticipate any significant problems with transportation arrangements or available time to travel to the study site over the next 2 months. Agree (if the subject is female and of child bearing potential) to use birth control Exclusion Criteria: Currently receiving treatment for AUD Significant alcohol withdrawal symptoms Coexisting moderate to severe substance use disorder other than cannabis and nicotine Urine toxicology screen positive drugs of abuse except for cannabis Treated with pharmacotherapy for AUD or a carbonic anhydrase inhibitor in past 30 days Compelled to alcohol treatment by the juvenile justice system or has probation or parole requirements that might interfere with study participation History of liver disease or have clinically significant abnormal laboratory values History of renal impairment or renal stones, narrow angle glaucoma or pheochromocytoma, heart problems or defects, abnormal blood pressure, progressive neurodegenerative disorder, or clinically significant neurological disorders Clinically significant physical abnormalities per physical exam, hematological assessment, bilirubin concentration, or urinalysis Pregnancy, nursing, or refusal to use reliable birth control, if female Psychotropic medication use in the past 30 days Current or lifetime diagnosis of psychotic disorders Current bipolar disorder Current major depressive episode Ever attempted suicide Current (past year) suicidality risk Known sensitivity to atomoxetine Be anyone who in the opinion of the investigator could not be safely withdrawn from alcohol without medical detoxification Serious or unstable medical illness or any potentially life-threatening or progressive medical condition other than addiction that may compromise subject safety or study conduct Abnormal calculated creatinine clearance defined as < 80 mL/min Evidence of cirrhosis of the liver (albumin < 3.2 g/dL, or ascites by physical exam)

Ages Eligible for Study
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Minimum Age: 14 Years
Maximum Age: 20 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Atomoxetine<br>Atomoxetine (40 mg/day for 3 days then 80 mg/day thereafter) during a 6-week medication trial | Drug: Atomoxetine<br>* Participants randomized to receive the study medication, atomoxetine (brand name: Straterra) for 6-weeks (40 mg/day for 3 days then 80 mg/day thereafter). A comparator group will receive placebo (sugar pills).<br>* Other names: Strattera;|
| Placebo Comparator: Placebo<br>Identical matching placebo capsules | Drug: Placebo<br>* Matching placebo (sugar pill)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Completion rates | Percentage of youth who complete the active medication phase will determine feasibility. | 6-week active treatment phase | 
| Acceptability of the study medication | Study withdrawal and the Client Satisfaction Questionnaire (CSQ-8), which ranges in scores from 8-32 (higher scores indicates higher satisfaction), will determine acceptability. | 6-week active treatment phase | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Alcohol Craving | The primary measure of alcohol craving will be the following single-item: How strong is your craving to drink alcohol? Scores range from 0 (None) to 20 (Extremely Strong). | 6-week active treatment phase |