Smoking Cessation, Stress, Sleep Disturbance, Nausea
Conditions
Brief summary
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.
Interventions
DRUGVarenicline Pill
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
DRUGHydroxyzine Pill
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.
Sponsors
Foundation for a Smoke Free World INC
Rose Research Center, LLC
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Open-label, single group study.
Eligibility
Sex/Gender
ALL
Age
19 Years to 65 Years
Healthy volunteers
Yes
Inclusion criteria
1. Has signed the consent form and is able to read and understand the information provided in the consent form. 2. Is 19 to 65 years of age (inclusive) at screening. 3. Smokes at least 10 commercially available cigarettes per day for the last 12 months. 4. Has an expired air carbon monoxide reading of at least 10 ppm at screening. 5. Express a desire to quit smoking within the next 30 days at screening. 6. Willing and able to comply with the requirements of the study. 7. Participant owns a smart phone with text message and data capabilities.
Exclusion criteria
1. 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). 2. 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. 3. High blood pressure (systolic \> 150 mmHg or diastolic \>95 mmHg) at screening. 4. Body mass index (BMI) less than 15.0 kg/m2 or greater than 40.0 kg/m2. 5. 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. 6. Has received psychotherapy or behavioral treatments potentially impacting symptoms of depression, anxiety, or nicotine withdrawal within 30 days of screening, or during the study. 7. Taking antidepressants, psychoactive medications (e.g. antipsychotics, benzodiazepines, hypnotics) or medications that prolong QTc. 8. Positive urine drug test for cocaine, marijuana, opiates, amphetamines or methamphetamines. 9. 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. 10. Pregnant or nursing (by self-report) or has a positive pregnancy test.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in 10-item Perceived Stress Scale (PSS-10) Following Smoking Cessation (While Taking Arenicline and Hydroxyzine). | Weeks 1, 2, 4, 8, 12 | 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. |
| Changes in Anxiety Using the 6-item State-Trait Anxiety Inventory (STAI) | Weeks 1, 2, 4, 8, 12 | 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. |
| Changes in Depression Using the Patient Health Questionnaire (PHQ-9) | Weeks 1, 2, 4, 8, 12 | 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Effects of Varenicline on Self-reported Smoking Reduction Prior to the Quit Date | 7 Days | 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. |
Countries
United States
Participant flow
Recruitment details
The study was conducted in both the Raleigh, NC and Charlotte, NC offices of Rose Research Center. Enrollment started on 17 June 2019 and ended on 16 September 2019.
Participants by arm
| Arm | Count |
|---|---|
| Hydroxyzine and Varenicline 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.
Varenicline Pill: 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
Hydroxyzine Pill: 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. | 26 |
| Total | 26 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Lost to Follow-up | 5 |
| Overall Study | Non-Compliance | 1 |
Baseline characteristics
| Characteristic | Hydroxyzine and Varenicline |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 26 Participants |
| Age, Continuous | 42.115 years STANDARD_DEVIATION 11.25 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 26 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 7 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 18 Participants |
| Region of Enrollment United States | 26 participants |
| Sex: Female, Male Female | 11 Participants |
| Sex: Female, Male Male | 15 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 26 |
| other Total, other adverse events | 21 / 26 |
| serious Total, serious adverse events | 0 / 26 |
Outcome results
Primary
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.
Time frame: Weeks 1, 2, 4, 8, 12
Population: The number of participants changes based on dropouts.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Hydroxyzine and Varenicline | Change in 10-item Perceived Stress Scale (PSS-10) Following Smoking Cessation (While Taking Arenicline and Hydroxyzine). | Change in PPS-10 from BL to Week 1 | -1.38 score on a scale | Standard Deviation 2.37 |
| Hydroxyzine and Varenicline | Change in 10-item Perceived Stress Scale (PSS-10) Following Smoking Cessation (While Taking Arenicline and Hydroxyzine). | Change in PPS-10 from BL to Week 2 | -1.48 score on a scale | Standard Deviation 3 |
| Hydroxyzine and Varenicline | Change in 10-item Perceived Stress Scale (PSS-10) Following Smoking Cessation (While Taking Arenicline and Hydroxyzine). | Change in PPS-10 from BL to Week 4 | -1.55 score on a scale | Standard Deviation 2.65 |
| Hydroxyzine and Varenicline | Change in 10-item Perceived Stress Scale (PSS-10) Following Smoking Cessation (While Taking Arenicline and Hydroxyzine). | Change in PPS-10 from BL to Week 8 | -2.05 score on a scale | Standard Deviation 3.58 |
| Hydroxyzine and Varenicline | Change in 10-item Perceived Stress Scale (PSS-10) Following Smoking Cessation (While Taking Arenicline and Hydroxyzine). | Change in PPS-10 from BL to Week 12 | -2.75 score on a scale | Standard Deviation 3.43 |
Primary
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.
Time frame: Weeks 1, 2, 4, 8, 12
Population: The number of participants changes based on dropouts.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Hydroxyzine and Varenicline | Changes in Anxiety Using the 6-item State-Trait Anxiety Inventory (STAI) | Change in STAI from BL to Week 1 | -0.54 score on a scale | Standard Deviation 2.67 |
| Hydroxyzine and Varenicline | Changes in Anxiety Using the 6-item State-Trait Anxiety Inventory (STAI) | Change in STAI from BL to Week 2 | -1.09 score on a scale | Standard Deviation 3.79 |
| Hydroxyzine and Varenicline | Changes in Anxiety Using the 6-item State-Trait Anxiety Inventory (STAI) | Change in STAI from BL to Week 4 | -0.86 score on a scale | Standard Deviation 4.54 |
| Hydroxyzine and Varenicline | Changes in Anxiety Using the 6-item State-Trait Anxiety Inventory (STAI) | Change in STAI from BL to Week 8 | -1.82 score on a scale | Standard Deviation 3.35 |
| Hydroxyzine and Varenicline | Changes in Anxiety Using the 6-item State-Trait Anxiety Inventory (STAI) | Change in STAI from BL to Week 12 | -1.65 score on a scale | Standard Deviation 3.59 |
Primary
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
Time frame: Weeks 1, 2, 4, 8, 12
Population: The number of participants changes based on dropouts.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Hydroxyzine and Varenicline | Changes in Depression Using the Patient Health Questionnaire (PHQ-9) | Change in PHQ-9 from BL to Week 1 | -0.15 score on a scale | Standard Deviation 1.12 |
| Hydroxyzine and Varenicline | Changes in Depression Using the Patient Health Questionnaire (PHQ-9) | Change in PHQ-9 from BL to Week 2 | 0.63 score on a scale | Standard Deviation 2.16 |
| Hydroxyzine and Varenicline | Changes in Depression Using the Patient Health Questionnaire (PHQ-9) | Change in PHQ-9 from BL to Week 4 | 0.43 score on a scale | Standard Deviation 2.95 |
| Hydroxyzine and Varenicline | Changes in Depression Using the Patient Health Questionnaire (PHQ-9) | Change in PHQ-9 from BL to Week 8 | -0.27 score on a scale | Standard Deviation 2.07 |
| Hydroxyzine and Varenicline | Changes in Depression Using the Patient Health Questionnaire (PHQ-9) | Change in PHQ-9 from BL to Week 12 | -0.41 score on a scale | Standard Deviation 1.87 |
Secondary
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.
Time frame: 7 Days
Population: The participants are divided as to whether they were successful in quitting smoking combustible cigarettes.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Hydroxyzine and Varenicline | Effects of Varenicline on Self-reported Smoking Reduction Prior to the Quit Date | -9.14 Cigs smoked per day | Standard Deviation 2.29 |
| Hydroxyzine and Varenicline -- Unsuccessful in Quitting Smoking | Effects of Varenicline on Self-reported Smoking Reduction Prior to the Quit Date | -5.53 Cigs smoked per day | Standard Deviation 6.8 |
Secondary
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.
Time frame: 7 Days
Population: The participants are divided as to whether they were successful in quitting smoking combustible cigarettes.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Hydroxyzine and Varenicline | Effects of Varenicline on Self-reported Smoking Reduction Prior to the Quit Date | -11.00 CO in ppm | Standard Deviation 8.28 |
| Hydroxyzine and Varenicline -- Unsuccessful in Quitting Smoking | Effects of Varenicline on Self-reported Smoking Reduction Prior to the Quit Date | -2.12 CO in ppm | Standard Deviation 10.02 |