Cytisine for Smoking Cessation

Study Overview
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Brief Summary
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The goal of this clinical trial is to evaluate the safety and effectiveness of cytisine as a smoking cessation treatment in individuals with concurrent alcohol use disorder.

Official Title
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Cytisine: Testing Its Potential as a Therapeutic Strategy for Smoking Cessation Among People With Concurrent Alcohol Use Disorder

Conditions
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Tobacco Use Disorder, Alcohol Use Disorder, Smoking Cessation

Intervention / Treatment
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* Drug: Cytisine
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Aged 18-65 years; Have TUD assessed by structured clinical interview for DSM-5; Have past year AUD (active) assessed by structured clinical interview for DSM-5; Report daily cigarette consumption in past month and expired carbon monoxide (CO) measurement ≥10ppm at screening; Have Fagerstrom Test of Nicotine Dependence (FTND55) score ≥4; Have motivation to quit within 30 days i.e. Contemplation Ladder56 score ≥7; Be willing and able to comply with all study procedural and assessment demands; Be able to provide voluntary written informed consent. Exclusion Criteria: Report prolonged smoking abstinence in the past month preceding screening; Be using other smoking cessation aids Enrolled in another smoking cessation program Be pregnant, breastfeeding, or intending to become pregnant or breastfeed; Exhibit suicidal thoughts or behavior in the past month; Enrolled in another study which would interfere with study procedures or represent a potential risk to the participant Have a serious unstable psychiatric or medical condition preventing participation in the trial. This includes some forms of schizophrenia, ischemic heart disease, heart failure, arterial hypertension (systolic BP above 150; diastolic BP above 100), cerebrovascular diseases, occlusion of blood vessels, kidney and/or liver disease, hyperthyroidism, ulcer, diabetes, Chromaffin tumours of the adrenal medulla, and gastroesophageal reflux disease (GERD)

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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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: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cytisine<br>Cytisine will be given as 1.5 mg tablet formulations for 25 days. The following treatment schedule will be followed: Days 1 to 3: 1.5 mg taken every 2 hours (6 pills (9 mg)/day) Days 4 to 12: 1.5 mg taken every 2.5 hours (5 pills (7.5 mg)/day) Days 13 to 16: 1.5 mg taken every 3 hours (4 pills (6 mg)/day) Days 17 to 20: Taper down to 1 tablet every 5 hours (3 pills (4.5 mg)/day) Days 21 to 25: Taper down to 1-2 tablets daily (1.5-3 mg/day) | Drug: Cytisine<br>* Cytisine is a nicotinic acetylcholine receptor partial agonist and is a natural health product approved by Health Canada. Cytisine has been used for a long time in Europe for smoking cessation.<br>|
| Placebo Comparator: Placebo<br>Placebo will be given following the same schedule as the Cytisine Arm. | Other: Placebo<br>* A placebo identical in appearance to cytisine will be used<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Frequency and type of adverse events | To assess the tolerability of cytisine | Total duration of trial (24 weeks) | 
| Rate of retention in the trial: number of sessions completed for each participant and number ofparticipants who withdraw | To assess the tolerability of cytisine | Total duration of trial (24 weeks) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Point-prevalence abstinence | Complete abstinence (not even a puff) during a designated time period (7 days) prior to assessment. This will be measured at each assessment point (e.g., 2 and 4wk). | Week 2 and week 4 | 
| Repeated point-prevalence abstinence | Point-prevalence abstinence at each consecutive assessment point. | Throughout study completion, up to 24 weeks. | 
| Prolonged abstinence | Complete abstinence (not even a puff) after an initial grace period; also known as sustained abstinence. | This period will end at the end of treatment (day 25) or at final follow-up. | 
| Prolonged abstinence with lapses | Prolonged abstinence after a grace period, but some smoking is allowed (e.g., no more than 5 cigarettes; fewer than seven consecutive days of smoking). | This period will end at the end of treatment (day 25) or at final follow-up. | 
| Continuous Abstinence | Complete abstinence (not even a puff) beginning on the TQD (i.e., with no grace period) and lasting until the assessment from target quit date (week 2) to end of treatment (day 25) and at final follow up. | Throughout study completion, up to 24 weeks. | 
| Physical dependence to Nicotine in Participants | The Fagerstrom Test for Nicotine Dependence (FTND) will be used to assess physical dependence in participants. | Throughout study duration (24 weeks) | 
| Nicotine Withdrawal Symptoms in Participants | The Minnesota Nicotine Withdrawal Scale (MNWS) will be used to assess nicotine withdrawal symptoms. | Throughout study duration (24 weeks) | 
| Nicotine Craving in Participants | Tiffany Questionnaire of Smoking Urges (QSU) will be used to assess nicotine craving. | Throughout study duration (24 weeks) |