Alcohol Use Disorder
Conditions
Brief summary
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
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.
Interventions
DRUGAtomoxetine
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).
DRUGPlacebo
Matching placebo (sugar pill)
Sponsors
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Brown University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
14 Years to 20 Years
Healthy volunteers
No
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)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Completion Rates | 6-week active treatment phase | Number and percentage of youth who complete the active medication phase will determine feasibility. |
| Number of Participants Who Rate Their Treatment Experience in the Satisfactory or Highly Satisfactory Range on the CSQ-8 | 6-week active treatment phase | The Client Satisfaction Questionnaire (CSQ-8), which ranges in scores from 8 to 32 (higher scores indicate higher satisfaction), will determine acceptability. Treatment satisfaction will be considered acceptable if the number and percentage of subjects who rate their treatment experience in the satisfactory or highly satisfactory range on the CSQ-8 is ≥ 80%. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Alcohol Craving | Alcohol craving was assessed during a laboratory alcohol-cue exposure paradigm, at week 5. Participants rated their alcohol craving immediately following exposure to alcohol and water cues. The outcomes measure is craving after alcohol cue exposure. | The primary measure of alcohol craving is the number and percentage of participants who report any level of alcohol craving during a laboratory alcohol-cue exposure paradigm using the following single item: How strong is your craving to drink alcohol? Scores range from 0 (None) to 20 (Extremely Strong). Individuals who endorse any level of alcohol craving (e.g., \> 1) are considered to experience craving. Individuals who do not report any alcohol craving (e.g., 0) will be regarded as non-craving. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Atomoxetine Atomoxetine (40 mg/day for 3 days then 80 mg/day thereafter) during a 6-week medication trial | 21 |
| Placebo Identical matching placebo capsules | 21 |
| Total | 42 |
Baseline characteristics
| Characteristic | Total | Placebo | Atomoxetine |
|---|---|---|---|
| Age, Continuous | 18.9 Years STANDARD_DEVIATION 0.08 | 18.9 Years STANDARD_DEVIATION 0.7 | 18.8 Years STANDARD_DEVIATION 0.8 |
| Days Abstinent from Alcohol (% of Days) | 63.61 Percent of Days STANDARD_DEVIATION 13.82 | 61.57 Percent of Days STANDARD_DEVIATION 16.67 | 65.65 Percent of Days STANDARD_DEVIATION 10.26 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 10 Participants | 4 Participants | 6 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 32 Participants | 17 Participants | 15 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Heavy Drinking Days (%) | 26.96 Percent of Days STANDARD_DEVIATION 12.05 | 27.89 Percent of Days STANDARD_DEVIATION 12.61 | 26.02 Percent of Days STANDARD_DEVIATION 10.69 |
| Number of Standard Alcohol Drinks per Drinking Day | 5.14 Drinks per Drinking Day STANDARD_DEVIATION 2.23 | 4.72 Drinks per Drinking Day STANDARD_DEVIATION 1.96 | 5.57 Drinks per Drinking Day STANDARD_DEVIATION 2.45 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 7 Participants | 5 Participants | 2 Participants |
| Race (NIH/OMB) Black or African American | 6 Participants | 0 Participants | 6 Participants |
| Race (NIH/OMB) More than one race | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 28 Participants | 15 Participants | 13 Participants |
| Region of Enrollment United States | 42 participants | 21 participants | 21 participants |
| Sex: Female, Male Female | 22 Participants | 11 Participants | 11 Participants |
| Sex: Female, Male Male | 20 Participants | 10 Participants | 10 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 21 | 0 / 21 |
| other Total, other adverse events | 19 / 21 | 19 / 21 |
| serious Total, serious adverse events | 0 / 21 | 0 / 21 |
Outcome results
Primary
Completion Rates
Number and percentage of youth who complete the active medication phase will determine feasibility.
Time frame: 6-week active treatment phase
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Atomoxetine | Completion Rates | 17 Participants |
| Placebo | Completion Rates | 18 Participants |
Primary
Number of Participants Who Rate Their Treatment Experience in the Satisfactory or Highly Satisfactory Range on the CSQ-8
The Client Satisfaction Questionnaire (CSQ-8), which ranges in scores from 8 to 32 (higher scores indicate higher satisfaction), will determine acceptability. Treatment satisfaction will be considered acceptable if the number and percentage of subjects who rate their treatment experience in the satisfactory or highly satisfactory range on the CSQ-8 is ≥ 80%.
Time frame: 6-week active treatment phase
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Atomoxetine | Number of Participants Who Rate Their Treatment Experience in the Satisfactory or Highly Satisfactory Range on the CSQ-8 | 21 Participants |
| Placebo | Number of Participants Who Rate Their Treatment Experience in the Satisfactory or Highly Satisfactory Range on the CSQ-8 | 19 Participants |
Secondary
Alcohol Craving
The primary measure of alcohol craving is the number and percentage of participants who report any level of alcohol craving during a laboratory alcohol-cue exposure paradigm using the following single item: How strong is your craving to drink alcohol? Scores range from 0 (None) to 20 (Extremely Strong). Individuals who endorse any level of alcohol craving (e.g., \> 1) are considered to experience craving. Individuals who do not report any alcohol craving (e.g., 0) will be regarded as non-craving.
Time frame: Alcohol craving was assessed during a laboratory alcohol-cue exposure paradigm, at week 5. Participants rated their alcohol craving immediately following exposure to alcohol and water cues. The outcomes measure is craving after alcohol cue exposure.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Atomoxetine | Alcohol Craving | 5 Participants |
| Placebo | Alcohol Craving | 16 Participants |