A Dose Response Effect of Atomoxetine to the Acute Effects of Alcohol (ATX_COMT)

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

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.

Study Overview

• Status: Terminated
• Conditions: Alcohol Craving; Mood Changes
• Intervention / Treatment: Drug: Atomoxetine, Strattera

• Study Type: Interventional
• Enrollment (Actual): 86
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Colorado
    • Boulder, Colorado, United States, 80309
      • GCRC, University of Colorado Boulder

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years to 45 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criterion:

1. Males and females age 21 to 35, as verified upon the presentation of a valid driver's license;
2. Must drink alcohol at least twice a week and have a minimum of 3 drinks per occasion (2 for women);
3. 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;
4. No history of alcohol treatment or desire for treatment;
5. Not currently take medications that are contraindicated for concurrent use with alcohol;
6. 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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Sugar Pill	Drug: Atomoxetine, Strattera; 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.
Experimental: Atomoxetine 40 mg	Drug: Atomoxetine, Strattera; 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.
Experimental: Atomoxetine 60 mg	Drug: Atomoxetine, Strattera; 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.
Experimental: Atomoxetine 80 mg	Drug: Atomoxetine, Strattera; 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.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: University of Colorado, Boulder
• Collaborators: National Institute on Alcohol Abuse and Alcoholism (NIAAA); National Center for Research Resources (NCRR)
• Investigators: Principal Investigator: Heather M Haughey, Ph.D., University of Colorado, Boulder

Study record dates

Study Major Dates

• Study Start: June 1, 2005
• Primary Completion (Actual): December 1, 2007
• Study Completion (Actual): December 1, 2007

Study Registration Dates

• First Submitted: July 12, 2011
• First Submitted That Met QC Criteria: August 2, 2011
• First Posted (Estimate): August 3, 2011

Study Record Updates

• Last Update Posted (Estimate): August 3, 2011
• Last Update Submitted That Met QC Criteria: August 2, 2011
• Last Verified: August 1, 2011

More Information

Terms related to this study

• Keywords: craving; alcohol; mood; optimum dose of atomoxetine
• Additional Relevant MeSH Terms: 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: B5089; M01RR000051 (NIH); K01AA015331 (NIH)