Reduced Nicotine Cigarettes in Smokers With Mood and Anxiety Disorders

Study Overview
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Brief Summary
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The overall aim of this project is to evaluate the effect of progressive nicotine reduction in cigarettes on smoking behavior, toxin exposure and psychiatric symptoms in smokers with comorbid mood and/or anxiety disorders. Smokers with mood and/or anxiety disorder will smoke research cigarettes that will contain either a) nicotine content similar to their preferred usual brand of cigarettes, or b) nicotine content per cigarette that is progressively reduced from approximately 11.6 mg to 0.2 mg per cigarette over 18 weeks. It is our hypothesis that nicotine intake will decline as a function of cigarette nicotine content in the Reduced Nicotine Content group without significant increases in tobacco smoke exposure, severity of nicotine withdrawal symptoms, mood and anxiety symptomatology or protocol non-adherence over time in the Reduced Nicotine Content group as compared with the control group.

Detailed Description
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The overall aim of this project is to evaluate the effect of progressive nicotine reduction in cigarettes on smoking behavior, toxicant exposure and psychiatric symptoms in smokers with comorbid mood and/or anxiety disorders. To do so, we will randomly assign 200 adult smokers with a unipolar mood and/or anxiety disorder within the past year to smoke research cigarettes that will contain either a) Usual Nicotine Content (UNC): nicotine content similar to their preferred usual brand of cigarettes, or b) Reduced Nicotine Content (RNC): nicotine content per cigarette is progressively reduced from approximately 11.6 mg to 0.2 mg per cigarette over 18 weeks. All subjects will participate in baseline periods prior to double-blind randomization to assess normal smoking behavior and then to establish ability to tolerate research cigarettes prior to randomization. A total of 280 participants will be enrolled in the study at two sites with the aim of randomizing 200 who complete the baseline phase. 100 participants will be enrolled in the randomized phase at Penn State Hershey and 100 at the Massachusetts General Hospital site. Participants will be started on the study protocol during Baseline I and Baseline II but will be removed from the study if they are not able to comply with the protocol. We expect that approximately 40 participants at each site drop out from the study prior to randomization (due to inability to comply with study protocol). It is our hypothesis that nicotine intake, as measured by plasma cotinine concentration, will decline as a function of cigarette nicotine content in the RNC group. Further, it is our hypothesis that by gradually reducing the nicotine content of the cigarettes in a step-wise fashion, there will not be significant increases in biomarkers of tobacco smoke exposure, severity of nicotine withdrawal symptoms, mood and anxiety symptomatology or protocol non-adherence over time in the experimental group (RNC) as compared with the UNC control group.

Official Title
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Reduced Nicotine Cigarettes in Smokers With Mood and Anxiety Disorders

Conditions
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Tobacco Dependence

Intervention / Treatment
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* Drug: Reduced Nicotine Content Cigarettes
* Drug: Usual Nicotine Content Cigarettes


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Smoke >4 cigarettes/day for at least a year No quit attempt in prior month Not planning to quit smoking within next 6 months Plan to live in local area for next 8 months Meet diagnostic criteria for a current or lifetime Anxiety Disorder or Mood Disorder as determined by the Mini-international Neuropsychiatric Interview Read and write in English Women not pregnant or nursing and taking steps to avoid pregnancy Able to understand and consent to study procedures Exclusion Criteria: Unstable or significant medical condition such as Chronic Obstructive Pulmonary Disease or kidney failure Use of non-cigarette nicotine delivery product in the past week or smoking cessation medicine in prior month Currently reducing or planning to reduce cigarette consumption in next month Uncontrolled serious psychotic illness or substance abuse or inpatient treatment for these in the past 6 months Current suicide risk on clinical assessment Aged <18 or >65 History of difficulty providing blood samples (fainting, poor venous access) Unwilling to remain on one flavor of cigarette (regular or menthol) for the duration of the trial

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 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: Health Services Research
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Reduced Nicotine Content Cigarettes<br>The experimental group will smoke cigarettes with gradually Reduced Nicotine Content (11.6, 7.4, 3.3, 1.4, 0.7 and 0.2 mg per cigarette) cigarettes, with each nicotine level smoked for 3 weeks, except the lowest level which continues for 6 weeks | Drug: Reduced Nicotine Content Cigarettes<br>* Research cigarettes will have gradually reduced nicotine content<br>* Other names: Nicotine;|
| Placebo Comparator: Usual Nicotine Content Cigarettes<br>Research cigarettes with a usual nicotine content (around 11.6mg per cigarette) | Drug: Usual Nicotine Content Cigarettes<br>* Usual Nicotine Content Cigarettes<br>* Other names: Nicotine;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Plasma Cotinine Concentration | Plasma cotinine is a measure of daily nicotine exposure. Samples were measured in ng/mL. | Measured at the end of the last 3 weeks of randomization trial phase | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Quick Inventory of Depressive Symptomatology | A 16-item scale on depression symptoms. The scale range is 0-27 where 0 = Least Severe and 27 = Most Severe. | Measured at the end of the last 3 weeks of randomization trial phase | 
| Perceived Stress Scale | 10-item questionnaire measuring the degree to which life situations are appraised stressful. Scale range is 0-40. Higher scores indicate more stress. | Measured at the end of the last 3 weeks of randomization trial phase | 
| Minnesota Nicotine Withdrawal Scale | This 8-item scale measures nicotine withdrawal symptoms and the scale range is from 0-32. Higher scores indicate higher severity. | Measured at the end of the last 3 weeks of randomization trial phase | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Smoking, Nicotine