Cytisine for Smoking Cessation

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

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.

Study Overview

• Status: Recruiting
• Conditions: Smoking Cessation; Tobacco Use Disorder; Alcohol Use Disorder
• Intervention / Treatment: Drug: Cytisine; Other: Placebo

• Study Type: Interventional
• Enrollment (Anticipated): 48
• Phase: Phase 4

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada, M5S 2S1
      • Recruiting
      • Center for Addiction and Mental Health

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cytisine; 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; 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.
Placebo Comparator: Placebo; Placebo will be given following the same schedule as the Cytisine Arm.	Other: Placebo; A placebo identical in appearance to cytisine will be used

What is the study measuring?

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)

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Tertiary Endpoints to evaluate the impact of cytisine vs. placebo on anxiety.	Anxiety will be measured through the General Anxiety Disorder-7 (GAD-7) questionnaire.	Throughout study duration (24 weeks)
Tertiary Endpoints to evaluate the impact of cytisine vs. placebo on mood.	Mood will be measured by the Patient Health Questionnaire-9 (PHQ-9).	Throughout study duration (24 weeks)
Tertiary Endpoints to evaluate the impact of cytisine vs. placebo on Quality of Life.	Quality of Life will be measured through the WHO Disability Assessment Schedule (WHODAS).	Throughout study duration (24 weeks)
Tertiary Endpoints to evaluate the impact of cytisine vs. placebo on drinking by collecting the number of drinking days in participants.	Number of drinking days and drinks per day/drinking day will be collected.	Throughout study duration (24 weeks)
Tertiary Endpoints to evaluate the impact of cytisine vs. placebo on drinking by measuring the proportion of heavy drinking days in participants.	Percent of heavy drinking days (5+/4+ males/females)/very heavy drinking days (10+/8+ males/females) per week and per month will be collected.	Throughout study duration (24 weeks)
Tertiary Endpoints to evaluate the impact of cytisine vs. placebo on drinking by measuring the proportion of participants without heavy drinking days.	Percent of subjects who are abstinent, percent of subjects with no heavy drinking days and percent of days abstinent will be collected.	Throughout study duration (24 weeks)

Collaborators and Investigators

• Sponsor: Centre for Addiction and Mental Health

Study record dates

Study Major Dates

• Study Start (Actual): February 8, 2023
• Primary Completion (Anticipated): January 1, 2024
• Study Completion (Anticipated): June 1, 2024

Study Registration Dates

• First Submitted: January 24, 2023
• First Submitted That Met QC Criteria: February 6, 2023
• First Posted (Actual): February 15, 2023

Study Record Updates

• Last Update Posted (Actual): April 6, 2023
• Last Update Submitted That Met QC Criteria: April 4, 2023
• Last Verified: April 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Chemically-Induced Disorders; Pathologic Processes; Drinking Behavior; Alcohol-Related Disorders; Substance-Related Disorders; Alcohol Drinking; Alcoholism; Disease; Tobacco Use Disorder
• Other Study ID Numbers: 054-2022

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No