Enhancing the Effects of Adolescent Alcohol Treatment With Atomoxetine

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Alcohol Use Disorder
• Intervention / Treatment: Drug: Placebo; Drug: Atomoxetine

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 42
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Robert Miranda, PhD; Phone Number: 401 863-6658; Email: Robert_Miranda_Jr@brown.edu
• Study Contact Backup: Name: Hayley Treloar Padovano, PhD; Phone Number: 401 863-6623; Email: Hayley_Treloar@brown.edu

Study Locations

• United States
  • Rhode Island
    • Providence, Rhode Island, United States, 02903
      • Brown University Center for Alcohol and Addiction Studies

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 20 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; Identical matching placebo capsules	Drug: Placebo; Matching placebo (sugar pill)
Experimental: Atomoxetine; Atomoxetine (40 mg/day for 3 days then 80 mg/day thereafter) during a 6-week medication trial	Drug: Atomoxetine; 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).; Other Names: Strattera

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Brown University
• Collaborators: National Institute on Alcohol Abuse and Alcoholism (NIAAA)
• Investigators: Principal Investigator: Robert Miranda, PhD, Brown University

Study record dates

Study Major Dates

• Study Start (Actual): May 6, 2021
• Primary Completion (Anticipated): June 1, 2023
• Study Completion (Anticipated): June 1, 2023

Study Registration Dates

• First Submitted: August 28, 2020
• First Submitted That Met QC Criteria: September 21, 2020
• First Posted (Actual): September 25, 2020

Study Record Updates

• Last Update Posted (Actual): March 22, 2023
• Last Update Submitted That Met QC Criteria: March 21, 2023
• Last Verified: March 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Chemically-Induced Disorders; Alcohol-Related Disorders; Substance-Related Disorders; Alcoholism; Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Adrenergic Uptake Inhibitors; Atomoxetine Hydrochloride
• Other Study ID Numbers: 1805002051; K24AA026326 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Data will be uploaded into the appropriate NIH repository as required.
• IPD Sharing Time Frame: Within 12-months of publication
• IPD Sharing Access Criteria: Any investigator who requests access in writing will be provided with the requested information.
• IPD Sharing Supporting Information Type: SAP; ICF; ANALYTIC_CODE

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes