Atomoxetine's Effects On Nicotine Response And Stress Response In Smokers

• ClinicalTrials.gov Identifier: NCT02046551
• Recruitment Status: Withdrawn
• First Posted: January 27, 2014
• Last Update Posted: May 22, 2017
• Sponsor: Yale University
• Collaborator: VA Office of Research and Development
• Information provided by (Responsible Party): Yale University

Study Description

Brief Summary:

The purpose of this study is to evaluate atomoxetine's effects on the rewarding and reinforcing effects of nicotine in a controlled human laboratory study with 24 otherwise healthy nicotine dependent subjects. It is hypothesized that atomoxetine will attenuate the negative effects of nicotine.

Condition or disease	Intervention/treatment	Phase
Nicotine Dependence	Drug: Atomoxetine; Drug: Placebo	Phase 1; Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 0 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Treatment
• Study Start Date: April 2014
• Estimated Primary Completion Date: February 2017
• Estimated Study Completion Date: February 2017

Arms and Interventions

Arm	Intervention/treatment
Placebo Comparator: Placebo; placebo	Drug: Placebo
Experimental: Atomoxetine; atomoxetine (40 mg/day)	Drug: Atomoxetine; Other Name: Strattera

Outcome Measures

Primary Outcome Measures :

1. Nicotine Effects Questionnaire [ Time Frame: Day 5 ]
   Subjects will rate 6 items that are related to nicotine effect on a 100 mm scale, "not at all" to "extremely." The items are feeling the drug strength, feel "good" drug effects, feel "bad" drug effects, feel jittery, feel stimulated, and head rush. This instrument is an abbreviated version of a visual analog scale (VAS) and allows rapid detection of nicotine effects.
2. Nicotine Effects Questionnaire [ Time Frame: Day 17 ]
   Subjects will rate 6 items that are related to nicotine effect on a 100 mm scale, "not at all" to "extremely." The items are feeling the drug strength, feel "good" drug effects, feel "bad" drug effects, feel jittery, feel stimulated, and head rush. This instrument is an abbreviated version of a visual analog scale (VAS) and allows rapid detection of nicotine effects.

Secondary Outcome Measures :

1. Center for Epidemiologic Studies Depression (CES-D) scale [ Time Frame: Day 5 ]
   The Center for Epidemiologic Studies Depression (CES-D) scale is a 20-item self-report measure of depressive symptoms. The range of scores is from 0 to 60, with higher scores reflecting increased depressive symptoms 41. The CES-D does not heavily depend on pathological items compared with other scales such as the Beck Depression Inventory and does not define clinical depression.
2. Positive and Negative Affect Schedule (PANAS ) [ Time Frame: Day 5 ]
   Positive and Negative Affect Schedule (PANAS ) is a 20-item scale that assesses both negative and positive affective states. Subjects rate adjectives describing affective states on a scale of 1 to 5 using a specified time period (e.g., now, today, past week etc.). Scores are then added up to generate negative and positive scale scores.
3. The Profile of Mood States (POMS) [ Time Frame: Day 5 ]
   The Profile of Mood States (POMS) is a 72-item questionnaire which consists of adjectives commonly used to describe momentary mood states. It has been found to be sensitive to the mood-altering effects of drugs including nicotine. POMS has a 5-point objective rating scale (0=not at all to 5=extremely). There are eight mood states that this scale measures: (1) Anger, (2) Anxiety, (3) Confusion, (4) Depression, (5) Elation, (6) Fatigue, (7) Friendliness and (8) Vigor. POMS will be used during each session to measure effects of atomoxetine or nicotine on mood.
4. Center for Epidemiologic Studies Depression (CES-D) scale [ Time Frame: Day 17 ]
   The Center for Epidemiologic Studies Depression (CES-D) scale is a 20-item self-report measure of depressive symptoms. The range of scores is from 0 to 60, with higher scores reflecting increased depressive symptoms 41. The CES-D does not heavily depend on pathological items compared with other scales such as the Beck Depression Inventory and does not define clinical depression.
5. Positive and Negative Affect Schedule (PANAS ) [ Time Frame: Day 17 ]
   Positive and Negative Affect Schedule (PANAS ) is a 20-item scale that assesses both negative and positive affective states 44. Subjects rate adjectives describing affective states on a scale of 1 to 5 using a specified time period (e.g., now, today, past week etc.). Scores are then added up to generate negative and positive scale scores.
6. The Profile of Mood States (POMS) [ Time Frame: Day 17 ]
   The Profile of Mood States (POMS) is a 72-item questionnaire which consists of adjectives commonly used to describe momentary mood states. It has been found to be sensitive to the mood-altering effects of drugs including nicotine. POMS has a 5-point objective rating scale (0=not at all to 5=extremely). There are eight mood states that this scale measures: (1) Anger, (2) Anxiety, (3) Confusion, (4) Depression, (5) Elation, (6) Fatigue, (7) Friendliness and (8) Vigor. POMS will be used during each session to measure effects of atomoxetine or nicotine on mood.
7. Symptom Checklist Form (SCF) [ Time Frame: Day 5 ]
   In order to monitor adverse events from the study medications, SCF will be administered before and after each session. SCF is a locally developed symptom checklist that includes possible side effects of study medications with each symptom being scored 1-5.
8. Symptom Checklist Form (SCF) [ Time Frame: Day 17 ]
   In order to monitor adverse events from the study medications, SCF will be administered before and after each session. SCF is a locally developed symptom checklist that includes possible side effects of study medications with each symptom being scored 1-5.
9. Nicotine Withdrawal Symptom Checklist (NWSC) [ Time Frame: Day 5 ]
   Smokers will be asked to rate several nicotine withdrawal symptoms on a likert scale visual analogue. There are 12 items responses range from 0, "not at all" to 3 "extremely".
10. Nicotine Withdrawal Symptom Checklist (NWSC) [ Time Frame: Day 17 ]
    Smokers will be asked to rate several nicotine withdrawal symptoms on a likert scale visual analogue. There are 12 items responses range from 0, "not at all" to 3 "extremely".

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 55 Years (Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• female and male smokers, not treatment seeking, aged 18 to 55 years;
• history of smoking daily for the past 12 months, at least 5 cigarettes daily;
• CO level > 10ppm;
• for women: not pregnant as determined by pregnancy screening, nor breast feeding, and using acceptable birth control methods.

Exclusion Criteria:

• history of major medical illnesses including asthma or chronic obstructive lung disease, history or current gastrointestinal ulcer, hepatic or renal impairment, coronary artery disease, cardiac rhythm disturbances or other medical conditions that the study physician deems contraindicated for the subject to be in the study;
• regular use of psychotropic medication (antidepressants, antipsychotics, or anxiolytics)
• recent psychiatric diagnosis and treatment for Axis I disorders including major depression, bipolar affective disorder, schizophrenia and panic disorder within the past year. We will make an exception for the following Axis I diagnoses: nicotine dependence and alcohol or other drug dependence (i.e., cocaine, opioid) as long as they are not meeting abuse or dependence criteria within the past 3 months for alcohol or drug use;
• use of drugs that slow heart rate (eg, beta-blockers), which may increase the risk of bradycardia and AV block, or NSAIDs, which may increase potential for developing ulcers/active or occult gastrointestinal bleeding;
• known allergy to atomoxetine

Contacts and Locations

Locations

United States, Connecticut

West Haven Veterans Affairs

West Haven, Connecticut, United States, 06515

Sponsors and Collaborators

Yale University

VA Office of Research and Development

Investigators

• Principal Investigator: Albert Arias, MD; Yale University

More Information

• Responsible Party: Yale University
• ClinicalTrials.gov Identifier: NCT02046551
• Other Study ID Numbers: 1305012021
• First Posted: January 27, 2014
• Last Update Posted: May 22, 2017
• Last Verified: May 2017

Keywords provided by Yale University:

nicotine; smoking; atomoxetine; stress

Additional relevant MeSH terms:

Tobacco Use Disorder; Substance-Related Disorders; Chemically-Induced Disorders; Mental Disorders; Atomoxetine Hydrochloride; Adrenergic Uptake Inhibitors; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Molecular Mechanisms of Pharmacological Action; Adrenergic Agents; Neurotransmitter Agents; Physiological Effects of Drugs