Smoking, Smoking Behaviors, Smoking Cessation
Conditions
Brief summary
The goal of this study is to assess varenicline vs. placebo for its effect on decreasing cue reactivity in light and intermittent smokers.
Detailed description
The study will consist of randomization to receive either varenicline or placebo over 6 weeks and include 5 study visits. Participants are offered an optional additional 6 weeks of active varenicline. Cue reactivity will be assessed in both a lab-based setting (viewing series of images and rating cravings) and in a real-world setting (text-based daily interaction).
Interventions
DRUGVarenicline
Chantix
DRUGPlacebo oral tablet
Placebo
Sponsors
Duke University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Intervention model description
2-arm randomized, placebo-controlled trial
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Age 18 years or above 2. Daily smoker using 10 or less cigarettes per day but a minimum of at least 1 cigarettes per week or 4 cigs/month. 3. Must be able to make it through a 24-hour period without nicotine withdrawal symptoms (specifically does not have new onset of irritability, headaches, insomnia, or intense cravings). 4. Willing to quit smoking in the next 30 days 5. Is able to provide written informed consent (in English) to participate in the study and is able to read/understand the procedures and study requirements. 6. Is willing to voluntarily sign and date an informed consent form that is approved by an institutional review board before the conduct of any study procedure. 7. If female and of childbearing potential, is willing to use medically acceptable contraceptive measures for the duration of the study. Acceptable methods of contraception include (1) surgical sterilization (such as tubal ligation or hysterectomy, (2) approved hormonal contraceptives (such as birth control pills, patches, implants or injections), (3) barrier methods (such as condom or diaphragm) used with a spermicide, or (4) an intrauterine device (IUD). Contraceptive measures such as rhythm method or Plan B™, sold for emergency use after unprotected sex, are not acceptable methods for routine use. 8. Have access to a cell phone that can send and receive SMS text messages.
Exclusion criteria
1. Use of a smoking cessation medication (e.g. nicotine replacement, varenicline, bupropion) in last 30 days. 2. Current use of tobacco product other than cigarettes (e.g. e-cigarettes, smokeless tobacco) in the last 30 days 3. Answer \> 0 on suicidality question of Patient Health Questionnaire (PHQ-9) Depression Scale 4. Active alcohol use disorder or hazardous drinking. This will be screened with the AUDIT-C, and positive scores (4 or greater for men and 3 or greater for women)54,55 will result in study clinician assessment and discretion. 5. Use of illicit drugs in the last month (marijuana, cocaine, opiates, benzodiazepines, and/or methamphetamine) 6. Severe symptomatic depression and or anxiety (study medical provider discretion) 7. Diagnosis of bipolar disorder, schizophrenia, PTSD and or adult ADHD (study medical provider discretion) 8. Chronic medical illness including diabetes with the use of insulin, Hemoglobin A1c \> 7 (study medical provider discretion), heart disease diagnosed by angiogram, or COPD diagnosed by pulmonary function testing and requiring an oxygen supply 9. Specific medications (Appendix 1) 10. Abnormal finding on physical exam (study medical provider discretion) 11. Positive Urine Pregnancy Test (women of child bearing potential only; QuickVue Urine Pregnancy)56 12. Positive Urine Toxicology-5 Screen (methamphetamine, cocaine, opiates, benzodiazepines, THC) 13. Unstable hypertension (Blood pressure \> 160/100) 14. Renal failure with active or pending hemodialysis
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Self-Reported Craving Level Via Lab-Based Cue Reactivity | Baseline, Visit 4 (week 6) | Participants were asked to self-report craving level to smoke on a scale of 1-10 with 1 corresponding to no craving and 10 corresponding to intense craving. Self-reported craving level was requested following presentation of multiple images on a screen over a 20 minute period. Four types of images were presented - neutral affect, negative affect, smoking and social images. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Self-Reported Craving Level Via Real-World Cue Reactivity | Baseline, Visit 4 (week 6) | Craving level in real world situations was assessed through electronic momentary assessment (EMA). Participants were instructed to send a text to the study team each time they experienced craving to smoke a cigarette. Self-report craving level to smoke was reported on a scale of 1-10 with 1 corresponding to no craving and 10 corresponding to intense craving. |
| Changes in Smoking | Screening visit, Visit 4 (week 6) | 7-day point prevalence smoking abstinence. This will be measured through self-reported daily smoking diaries and daily text messaging. |
| Medication Adherence | Screening visit, Visit 4 (week 6) | Medication adherence is measured by composite self-reported diaries and daily text messaging responses. |
| Medication Tolerance by Self-Reported Side Effects | Up to 12 weeks | Self-reported side effects (open ended survey questions) with a ranking scale of 1-2 (mild), 3-5 (moderate), and 6-7 (severe). Any side effect 3 or greater will be reviewed by a study medical provider. |
| Changes in Smoking Abstinence | Screening visit, Visit 4 (week 6) | 7-day point prevalence smoking abstinence confirmed by CO \<7ppm. This will be measured through biochemical confirmation (CO breath test). |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Varenicline Varenicline BID
Varenicline: Chantix | 6 |
| Placebo Placebo oral tablet: Placebo | 5 |
| Total | 11 |
Baseline characteristics
| Characteristic | Total | Varenicline | Placebo |
|---|---|---|---|
| Age, Continuous | 38.4 years STANDARD_DEVIATION 10.3 | 34.8 years STANDARD_DEVIATION 7.1 | 42.6 years STANDARD_DEVIATION 12.7 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 1 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 10 Participants | 5 Participants | 5 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 3 Participants | 2 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 6 Participants | 3 Participants | 3 Participants |
| Race (NIH/OMB) More than one race | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 1 Participants | 0 Participants | 1 Participants |
| Region of Enrollment United States | 11 participants | 6 participants | 5 participants |
| Sex: Female, Male Female | 6 Participants | 2 Participants | 4 Participants |
| Sex: Female, Male Male | 5 Participants | 4 Participants | 1 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 6 | 0 / 5 |
| other Total, other adverse events | 5 / 6 | 5 / 5 |
| serious Total, serious adverse events | 1 / 6 | 0 / 5 |
Outcome results
Primary
Change in Self-Reported Craving Level Via Lab-Based Cue Reactivity
Participants were asked to self-report craving level to smoke on a scale of 1-10 with 1 corresponding to no craving and 10 corresponding to intense craving. Self-reported craving level was requested following presentation of multiple images on a screen over a 20 minute period. Four types of images were presented - neutral affect, negative affect, smoking and social images.
Time frame: Baseline, Visit 4 (week 6)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Varenicline | Change in Self-Reported Craving Level Via Lab-Based Cue Reactivity | Baseline | 6.31 score on a scale | Standard Deviation 2.8 |
| Varenicline | Change in Self-Reported Craving Level Via Lab-Based Cue Reactivity | Week 6 | 2.56 score on a scale | Standard Deviation 2.11 |
| Placebo | Change in Self-Reported Craving Level Via Lab-Based Cue Reactivity | Baseline | 4.2 score on a scale | Standard Deviation 1.8 |
| Placebo | Change in Self-Reported Craving Level Via Lab-Based Cue Reactivity | Week 6 | 2.4 score on a scale | Standard Deviation 1.3 |
Secondary
Change in Self-Reported Craving Level Via Real-World Cue Reactivity
Craving level in real world situations was assessed through electronic momentary assessment (EMA). Participants were instructed to send a text to the study team each time they experienced craving to smoke a cigarette. Self-report craving level to smoke was reported on a scale of 1-10 with 1 corresponding to no craving and 10 corresponding to intense craving.
Time frame: Baseline, Visit 4 (week 6)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Varenicline | Change in Self-Reported Craving Level Via Real-World Cue Reactivity | Baseline | 7.15 score on a scale | Standard Deviation 1.1 |
| Varenicline | Change in Self-Reported Craving Level Via Real-World Cue Reactivity | Week 6 | 5.5 score on a scale | Standard Deviation 0.5 |
| Placebo | Change in Self-Reported Craving Level Via Real-World Cue Reactivity | Baseline | 6.7 score on a scale | Standard Deviation 1.8 |
| Placebo | Change in Self-Reported Craving Level Via Real-World Cue Reactivity | Week 6 | 8 score on a scale | Standard Deviation 0 |
Secondary
Changes in Smoking
7-day point prevalence smoking abstinence. This will be measured through self-reported daily smoking diaries and daily text messaging.
Time frame: Screening visit, Visit 4 (week 6)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Varenicline | Changes in Smoking | Baseline | 3.6 cigarettes per day | Standard Deviation 3.4 |
| Varenicline | Changes in Smoking | Week 6 | 0.5 cigarettes per day | Standard Deviation 0.8 |
| Placebo | Changes in Smoking | Baseline | 5.2 cigarettes per day | Standard Deviation 2.3 |
| Placebo | Changes in Smoking | Week 6 | 2.6 cigarettes per day | Standard Deviation 3.2 |
Secondary
Changes in Smoking Abstinence
7-day point prevalence smoking abstinence confirmed by CO \<7ppm. This will be measured through biochemical confirmation (CO breath test).
Time frame: Screening visit, Visit 4 (week 6)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Varenicline | Changes in Smoking Abstinence | Baseline | 9.5 ppm | Standard Deviation 11.1 |
| Varenicline | Changes in Smoking Abstinence | Week 6 | 2.6 ppm | Standard Deviation 1.5 |
| Placebo | Changes in Smoking Abstinence | Baseline | 10.2 ppm | Standard Deviation 3.7 |
| Placebo | Changes in Smoking Abstinence | Week 6 | 7.8 ppm | Standard Deviation 5.5 |
Secondary
Medication Adherence
Medication adherence is measured by composite self-reported diaries and daily text messaging responses.
Time frame: Screening visit, Visit 4 (week 6)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Varenicline | Medication Adherence | 91.6 Percent medication adherence | Standard Deviation 0.08 |
| Placebo | Medication Adherence | 90.3 Percent medication adherence | Standard Deviation 0.13 |
Secondary
Medication Tolerance by Self-Reported Side Effects
Self-reported side effects (open ended survey questions) with a ranking scale of 1-2 (mild), 3-5 (moderate), and 6-7 (severe). Any side effect 3 or greater will be reviewed by a study medical provider.
Time frame: Up to 12 weeks
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Varenicline | Medication Tolerance by Self-Reported Side Effects | Constipation | 1 Participants |
| Varenicline | Medication Tolerance by Self-Reported Side Effects | Dry Mouth | 1 Participants |
| Varenicline | Medication Tolerance by Self-Reported Side Effects | Nausea/Vomiting | 1 Participants |
| Varenicline | Medication Tolerance by Self-Reported Side Effects | Fatigue | 0 Participants |
| Varenicline | Medication Tolerance by Self-Reported Side Effects | Dizziness/Lightheadedness | 1 Participants |
| Varenicline | Medication Tolerance by Self-Reported Side Effects | Insomnia/Trouble Sleeping | 0 Participants |
| Varenicline | Medication Tolerance by Self-Reported Side Effects | Abnormal/Vivid Dreams | 1 Participants |
| Placebo | Medication Tolerance by Self-Reported Side Effects | Insomnia/Trouble Sleeping | 1 Participants |
| Placebo | Medication Tolerance by Self-Reported Side Effects | Abnormal/Vivid Dreams | 2 Participants |
| Placebo | Medication Tolerance by Self-Reported Side Effects | Nausea/Vomiting | 1 Participants |
| Placebo | Medication Tolerance by Self-Reported Side Effects | Constipation | 0 Participants |
| Placebo | Medication Tolerance by Self-Reported Side Effects | Dizziness/Lightheadedness | 0 Participants |
| Placebo | Medication Tolerance by Self-Reported Side Effects | Dry Mouth | 0 Participants |
| Placebo | Medication Tolerance by Self-Reported Side Effects | Fatigue | 2 Participants |