A Dose Response Effect of Atomoxetine to the Acute Effects of Alcohol

Study Overview
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Brief Summary
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This two-stage study will examine the effects of a 5 day course of atomoxetine (placebo, 40, 60 or 80 mg/day; Strattera) (a selective NE transporter (NET) inhibitor) on alcohol-elicited craving and sensitivity to alcohol. The novelty of this study is that of atomoxetine and the fact that it targets NET, neither of which has heretofore been examined in the context of alcohol dependence. It is hopeful that this pilot study, of 86 total individuals, will provide the PI with sufficient preliminary data to submit a subsequent R01 application to study atomoxetine and the involvement of specific single nucleotide polymorphisms within the NET gene on alcohol-related phenotypes in alcohol dependent and non-dependent populations. The long-term objective of this research is to develop more efficacious treatment interventions for alcohol abuse and dependence. Hypothesis 1: It is hypothesized that subjects who receive 40, 60 or 80 mg/day of atomoxetine for 5 days will demonstrate significantly less alcohol-elicited craving than subjects who receive a placebo. Hypothesis 2: It is hypothesized that subjects who receive 40, 60 or 80 mg/day of atomoxetine for 5 days will be less sensitive to the acute effects of alcohol (subjective intoxication) than subjects who receive a placebo.

Official Title
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A Pharmacotherapy Study: A Dose Response Effect of Atomoxetine on Alcohol-elicited Craving and Sensitivity to the Acute Effects of Alcohol

Conditions
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Alcohol Craving, Mood Changes

Intervention / Treatment
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* Drug: Atomoxetine, Strattera


Participation Criteria
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Eligibility Criteria
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Inclusion Criterion: Males and females age 21 to 35, as verified upon the presentation of a valid driver's license; Must drink alcohol at least twice a week and have a minimum of 3 drinks per occasion (2 for women); Must score 8 or higher on the Alcohol Use Disorders Identification Test (AUDIT; Babor et al., 1992). The AUDIT is a screening instrument used to identify persons whose alcohol consumption is characterized by moderate to heavy drinking; No history of alcohol treatment or desire for treatment; Not currently take medications that are contraindicated for concurrent use with alcohol; Female subjects must not be pregnant, as indicated by a pregnancy test that will be conducted immediately prior dispensing of medication. Exclusion Criterion: Subjects who have hypertension, tachycardia, cardiovascular disease, hepatic or renal impairment, pregnant or who are currently using MAO inhibitors, Albuterol or other pressor agents will be excluded from this study.

Ages Eligible for Study
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Minimum Age: 21 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Sugar Pill<br> | Drug: Atomoxetine, Strattera<br>* Atomoxetine at 0, 40, 60, 80 mg/day was given for 5 days, all subjects took two capsules per day for 5 days; all active dose groups received 40 mg/day for first 3 days and where then dose escalated to dosage group assigned.<br>|
| Experimental: Atomoxetine 40 mg<br> | Drug: Atomoxetine, Strattera<br>* Atomoxetine at 0, 40, 60, 80 mg/day was given for 5 days, all subjects took two capsules per day for 5 days; all active dose groups received 40 mg/day for first 3 days and where then dose escalated to dosage group assigned.<br>|
| Experimental: Atomoxetine 60 mg<br> | Drug: Atomoxetine, Strattera<br>* Atomoxetine at 0, 40, 60, 80 mg/day was given for 5 days, all subjects took two capsules per day for 5 days; all active dose groups received 40 mg/day for first 3 days and where then dose escalated to dosage group assigned.<br>|
| Experimental: Atomoxetine 80 mg<br> | Drug: Atomoxetine, Strattera<br>* Atomoxetine at 0, 40, 60, 80 mg/day was given for 5 days, all subjects took two capsules per day for 5 days; all active dose groups received 40 mg/day for first 3 days and where then dose escalated to dosage group assigned.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Alcohol Craving | Alcohol craving and sensitivity were measured with the AUQ, ARS, POMS, BAES and SHAS | Day 5 of medication | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Genetic moderation | To determine whether two functional SNPs within the COMT and DBH genes moderate the effects of EtOH and or atomoxetine. COMT Val158Met (G/A), Val > Met 2-4x plasma activity DBH -1021 C/T, C/C has 3x more plasma activity NET gene variants were also examined | day 5 of medication | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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alcohol, craving, mood, optimum dose of atomoxetine