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

Study Overview
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Brief Summary
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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.

Conditions
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Nicotine Dependence

Intervention / Treatment
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* Drug: Atomoxetine
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>placebo | Drug: Placebo<br> <br> |
| Experimental: Atomoxetine<br>atomoxetine (40 mg/day) | Drug: Atomoxetine<br> <br> * Other names: Strattera;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Nicotine Effects Questionnaire | 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. | Day 5 | 
| Nicotine Effects Questionnaire | 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. | Day 17 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Center for Epidemiologic Studies Depression (CES-D) scale | 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. | Day 5 | 
| Positive and Negative Affect Schedule (PANAS ) | 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. | Day 5 | 
| The Profile of Mood States (POMS) | 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. | Day 5 | 
| Center for Epidemiologic Studies Depression (CES-D) scale | 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. | Day 17 | 
| Positive and Negative Affect Schedule (PANAS ) | 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. | Day 17 | 
| The Profile of Mood States (POMS) | 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. | Day 17 | 
| Symptom Checklist Form (SCF) | 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. | Day 5 | 
| Symptom Checklist Form (SCF) | 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. | Day 17 | 
| Nicotine Withdrawal Symptom Checklist (NWSC) | 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. | Day 5 | 
| Nicotine Withdrawal Symptom Checklist (NWSC) | 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. | Day 17 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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nicotine, smoking, atomoxetine, stress