Efficacy and Tolerability of Combination Varenicline With Hydroxyzine as a Potential Smoking Cessation Treatment

Study Overview
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Brief Summary
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This open-label study will evaluate hydroxyzine, a first-generation antihistamine, combined with varenicline, to help smokers abstain from smoking during a 12-week trial period by diminishing the nausea, stress, anxiety, and sleep disturbances associated with the use of varenicline and with nicotine withdrawal.

Official Title
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Efficacy and Tolerability of Combination Varenicline With Hydroxyzine as a Potential Smoking Cessation Treatment

Conditions
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Smoking Cessation, Stress, Sleep Disturbance, Nausea

Intervention / Treatment
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* Drug: Varenicline Pill
* Drug: Hydroxyzine Pill


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Has signed the consent form and is able to read and understand the information provided in the consent form. Is 19 to 65 years of age (inclusive) at screening. Smokes at least 10 commercially available cigarettes per day for the last 12 months. Has an expired air carbon monoxide reading of at least 10 ppm at screening. Express a desire to quit smoking within the next 30 days at screening. Willing and able to comply with the requirements of the study. Participant owns a smart phone with text message and data capabilities. Exclusion Criteria: Is unhealthy or cannot participate in the study for any reason (e.g., medical, psychiatric, and/or social reason) as judged by the Investigator or designated medical staff based on all available assessments from the screening period (e.g., safety laboratory, vital signs, physical examination, ECG, concomitant medications and medical history). PHQ-9 score greater than 9, or a score greater than 0 on item #9 (Thoughts that you would be better off dead, or of hurting yourself in some way) at screening. High blood pressure (systolic > 150 mmHg or diastolic >95 mmHg) at screening. Body mass index (BMI) less than 15.0 kg/m2 or greater than 40.0 kg/m2. Coronary heart disease, structural cardiac disease, cardiac dysrhythmias, abnormal ECG (e.g. prolonged QTc), syncope, cardiac chest pain, or history of heart attack or heart failure. Has received psychotherapy or behavioral treatments potentially impacting symptoms of depression, anxiety, or nicotine withdrawal within 30 days of screening, or during the study. Taking antidepressants, psychoactive medications (e.g. antipsychotics, benzodiazepines, hypnotics) or medications that prolong QTc. Positive urine drug test for cocaine, marijuana, opiates, amphetamines or methamphetamines. Use of smokeless tobacco (chewing tobacco, snuff), cigars, pipes, hookah, e-cigarettes, nicotine replacement therapy or other smoking cessation treatments within 14 days of enrollment. Pregnant or nursing (by self-report) or has a positive pregnancy test.

Ages Eligible for Study
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Minimum Age: 19 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: Treatment
Intervention Model: Single Group Assignment
Interventional Model Description: Open-label, single group study.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Hydroxyzine and Varenicline<br>Participants enrolled in the study will take the FDA approved starter kit of varenicline for the first week of medication administration (0.5 mg nightly for days 1-3, then 0.5 mg twice daily for days 4-7). During the first week, participants will also receive hydroxyzine dosed in a similar manner, 50 mg nightly for the first 3 days, then twice daily, 25 mg in the morning and 50 mg at night. After the first week, participants will receive the FDA-approved dose of varenicline (1 mg twice daily) combined with hydroxyzine, 25 mg in the morning and 50 mg at nighttime. All medications will be dosed orally. | Drug: Varenicline Pill<br>* FDA approved starter kit of varenicline (0.5 mg nightly for days 1-3, then 0.5 mg twice daily for days 4-7) followed by FDA-approved dose of varenicline (1 mg twice daily) for the remaining 11 weeks<br>* Other names: Chantix;Drug: Hydroxyzine Pill<br>* For the first week, participants will receive 50 mg nightly for the first 3 days, then twice daily, 25 mg in the morning and 50 mg at night for the remaining 12 weeks.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in 10-item Perceived Stress Scale (PSS-10) Following Smoking Cessation (While Taking Arenicline and Hydroxyzine). | Stress levels in the last 30 days will be measured using the 10-item Perceived Stress Scale (PSS-10). The PSS-10 uses a 5-point scale (0 - never, 1 = almost never, 2 = once in a while, 3 = often, 4 = very often). Total scores range from 0 to 40. Scores ranging from 0-13 would be considered low stress. Scores ranging from 14-26 would be considered moderate stress. Scores ranging from 27-40 would be considered high perceived stress. | Weeks 1, 2, 4, 8, 12 | 
| Changes in Anxiety Using the 6-item State-Trait Anxiety Inventory (STAI) | Trait and state anxiety levels will be monitored for changes using the 6-item State-Trait Anxiety Inventory (STAI). All items are rated on a 4-point scale (1-Almost Never to 4-Almost Always). The range of scores is from 6 to 24. Higher scores indicate greater anxiety. | Weeks 1, 2, 4, 8, 12 | 
| Changes in Depression Using the Patient Health Questionnaire (PHQ-9) | Depression will be monitored for changes using the Patient Health Questionnaire (PHQ-9). The PHQ-9 uses a 4-point scale (Not at all = 0; Several days = 1;More than half the days = 2; Nearly every day = 3). The sum of the scores is calculated (Score range is 0 to 27): 1-4 Minimal depression 5-9 Mild depression 10-14 Moderate depression 15-19 Moderately severe depression 20-27 Severe depression | Weeks 1, 2, 4, 8, 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Effects of Varenicline on Self-reported Smoking Reduction Prior to the Quit Date | Previous research has shown that abstinence at the end of treatment is strongly predicted by the extent to which smokers spontaneously reduce ad libitum smoking in the initial weeks of pharmacotherapy that is initiated before the quit-smoking date. This measure will assess the extent of smoking reduction in participants during the initial seven days of treatment (prior to their planned quit date) - assessed via a self-report number of cigarettes per day. Data is recorded as a mean change. | 7 Days | 
| Effects of Varenicline on Self-reported Smoking Reduction Prior to the Quit Date | Previous research has shown that abstinence at the end of treatment is strongly predicted by the extent to which smokers spontaneously reduce ad libitum smoking in the initial weeks of pharmacotherapy that is initiated before the quit-smoking date. This measure will assess the extent of smoking reduction in participants during the initial seven days of treatment (prior to their planned quit date) - assessed via expired air carbon monoxide (CO). Data is recorded as a mean change. | 7 Days |