Cognitive Effects of Atomoxetine in Humans: Genetic Moderators

The overall goal of this study is to determine if atomoxetine treatment improves selective cognitive functions in abstinent cocaine users, compared to healthy controls. The study will also test if a functional variation of the NET promoter polymorphic region (NETpPR) moderates the cognitive effects of atomoxetine.

Study Overview

• Status: Completed
• Conditions: Addiction
• Intervention / Treatment: Drug: Sugar Pill; Drug: Atomoxetine

Detailed Description

This will be a double-blind, placebo-controlled, crossover study, with cocaine use (cocaine users vs. healthy controls) and NET AAGG4 status (L4/ L4 vs. L4/S4 or S4/ S4 genotype) as the between-subject factors. Similar to previous studies, we propose to compare individuals with two copies of the L4 allele to participants with at least one S4 allele because only less than two percent of the general population is homozygous for the S4 allele. Forty cocaine users and 40 healthy controls will participate in 3 test sessions, where they will be assigned to 40 mg atomoxetine, 80 mg atomoxetine, or placebo. Outcome measures will include physiological, subjective, and cognitive performance measures.

To date this study has 35 completers and currently in data analysis. (January 2016)

• Study Type: Interventional
• Enrollment (Actual): 35
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Connecticut
    • West Haven, Connecticut, United States, 06516
      • Department of Veterans Affairs

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years to 50 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Male and females, between the ages of 21 and 50;
• No current dependence or abuse of drugs of abuse or alcohol (except and tobacco);
• No current medical problems and normal ECG;
• For women, not pregnant as determined by pregnancy screening nor breast feeding, and using acceptable birth control methods.

Exclusion Criteria:

• Current major psychiatric illnesses including mood, psychotic, or anxiety disorders;
• History of major medical illnesses; including liver diseases, heart disease, or other medical conditions that the physician investigator deems contraindicated for the subject to be in the study;
• Known allergy to Atomoxetine;
• Use of Monoamine Oxidase inhibitor within the last month (clinically Atomoxetine administration is contraindicated with or within 2 weeks of discontinuation of Monoamine oxidase inhibitor therapy).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Atomoxetine; Atomoxetine compared to the sugar pill	Drug: Sugar Pill; Sugar pill compared to Atomoxetine 40mg and 80mg.; Other Names: placebo
Placebo Comparator: Sugar Pill; Sugar pill compared to atomoxetine	Drug: Atomoxetine; Atomoxetine 40mg and 80mg compared to the sugar pill; Other Names: Strattera

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rapid Visual Information Processing	Cognitive Test to determine the speed of Visual information. The CANTAB Rapid Visual Information Processing test (RVP) is a measure of sustained attention with a small working memory component (Sahakian and Owen, 1992). Digits are rapidly (100/minute) and pseudo-randomly presented for 7 minutes. Subjects are instructed to press when the third digit of a target sequence (e.g. 3-5-7) is displayed. Primary outcomes are indices of target discriminability (A') and response bias (B") and response latency to targets.	2 years
Rapid Visual Information Processing: Mean Correct Response Latency	Cognitive Test to determine the speed of Visual information. The CANTAB Rapid Visual Information Processing test (RVP) is a measure of sustained attention with a small working memory component (Sahakian and Owen, 1992). Digits are rapidly (100/minute) and pseudo-randomly presented for 7 minutes. Subjects are instructed to press when the third digit of a target sequence (e.g. 3-5-7) is displayed. Primary outcomes are indices of target discriminability (A') and response bias (B") and response latency to targets.	2 years

Collaborators and Investigators

• Sponsor: Yale University
• Investigators: Principal Investigator: Mehmet Sofuoglu, M.D., Ph.D., Yale University

Study record dates

Study Major Dates

• Study Start: December 1, 2011
• Primary Completion (Actual): July 1, 2013
• Study Completion (Actual): July 1, 2013

Study Registration Dates

• First Submitted: December 20, 2011
• First Submitted That Met QC Criteria: December 22, 2011
• First Posted (Estimate): December 23, 2011

Study Record Updates

• Last Update Posted (Actual): July 11, 2017
• Last Update Submitted That Met QC Criteria: June 8, 2017
• Last Verified: June 1, 2017

More Information

Terms related to this study

• Keywords: Abstinent cocaine users; cognitive testing
• Additional Relevant MeSH Terms: Compulsive Behavior; Impulsive Behavior; Behavior, Addictive; 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: 1103008235

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No