Nicotine is highly addictive: >95% of unaided attempts at smoking cessation fail by 6 months. Electronic (e)- cigarettes (vaping) are nicotine-delivery devices that may be useful in some individuals for smoking cessation but are not FDA-approved as a smoking cessation aid and long-term use may have uncertain health impacts. Evidence suggests that vaping nicotine may also raise cardiovascular and pulmonary disease risks. Many experts and professional societies recommend that vapers should also attempt to stop using nicotine e- cigarettes. However, treatments to aid e-cigarette cessation have yet to be identified or FDA-approved. This project will test whether cytisine, a partial nAChR agonist that reduces the severity of nicotine withdrawal symptoms while inhibiting nicotine reward effects in the brain, can promote cessation of e-cigarette use. Prior trials have shown cytisine's efficacy for smoking cessation, and it has been marketed as a smoking cessation aid in Europe for decades. Achieve Life Sciences has recently (past 3 years) expedited the US clinical development program for cytisine as a smoking cessation aid and now proposes to test for vaping cessation. This will be the first multicenter, randomized, placebo-controlled Pilot study conducted in daily nicotine e- cigarette users to evaluate the benefit and safety of cytisine as a vaping cessation aid. The primary objective is to assess if subjects randomized to 12 weeks of 3 mg cytisine three times a day (TID), vs placebo TID, have a higher prevalence of biochemically- verified nicotine vaping cessation from Week 9 to Week 12. Secondary objectives include assessment of cytisine vs placebo regarding: 1. Earlier vaping cessation initiated at Week 3- 6 or Week 6-9; 2. Vaping reduction, measured by weekly quantitative cotinine levels; 3. Testing moderation effects in efficacy outcomes across subgroups defined by demographic and baseline characteristics. The safety objective will compare the safety profile of cytisine vs placebo when administered for 12 weeks. This study will enroll 150 adult subjects (â¥18 years) at 8 US sites, who are daily nicotine e-cigarette users and not current cigarette smokers (confirmed by saliva cotinine and expired carbon monoxide [CO] levels), intending to quit vaping, and willing to set a quit date 7-14 days from the start of study treatment. Subjects will be randomly assigned (2:1) to one of two arms: (cytisine 3 mg TID N=100, or identical placebo TID N=50) for 12 weeks study treatment. All subjects will receive concurrent behavioral support for nicotine/vaping cessation during the study. Study treatment will be double-blind. Vaping status (abstinence) will be assessed by self-report after the planned quit target of 7-14 days post-randomization and assessed weekly from Week 2 through Week 12, including weekly biochemical verification via measurement of salivary cotinine levels. Expired CO levels will be monitored for smoking relapse. Subjects will be assessed for safety during Week 1 of treatment, and weekly thereafter, during the treatment period. Success will be measured as â¥20-30% cessation in the intervention group, and statistically significant (pâ¤0.1 or 0.05) cytisine benefit in other endpoints.
Public Health Relevance Statement: NARRATIVE Nicotine is highly addictive, and new electronic nicotine-delivery devices (e-cigarettes) have become popular but have uncertain long-term health impacts including potential cardiovascular and pulmonary disease risks and pulmonary inflammation. Effective pharmacotherapies for nicotine vaping cessation are a priority for public health. Cytisine is a natural compound that has been successfully used in Central and Eastern Europe as a smoking cessation aid for several decades, and in this project Achieve Life Sciences has proposed a pilot clinical study to test the benefit of a newly revised cytisine treatment regimen as a nicotine e-cigarette (vaping) cessation aid.
Project Terms: Adult; 21+ years old; Adult Human; adulthood; Biological Sciences; Biologic Sciences; Bioscience; Life Sciences; Brain; Brain Nervous System; Encephalon; Budgets; Carbon Monoxide; Cardiovascular Diseases; cardiovascular disorder; Clinical Protocols; Clinical Research; Clinical Study; Clinical Trials; Consent Forms; Consent Documents; Informed Consent Documents; Informed Consent Forms; Cotinine; Scotine; Counseling; Data Collection; Statistical Data Interpretation; Statistical Data Analyses; Statistical Data Analysis; statistical analysis; Double-Blind Method; Double-Blind Study; Double-Blinded; Double-Masked Method; Double-Masked Study; Pharmacotherapy; Drug Therapy; drug treatment; Pharmaceutical Preparations; Drugs; Medication; Pharmaceutic Preparations; drug/agent; Europe; Eastern Europe; Health; Immune system; allergic/immunologic body system; allergic/immunologic organ system; Laboratories; Lung diseases; Pulmonary Diseases; Pulmonary Disorder; Respiratory Disease; Respiratory System Disease; Respiratory System Disorder; disease of the lung; disorder of the lung; lung disorder; Nicotine; Nicotine Dependence; nicotine addiction; nicotine dependent; Nicotine Withdrawal; Pamphlets; Booklets; Brochures; Pilot Projects; pilot study; Placebos; Sham Treatment; sham therapy; Probability; Professional Organizations; professional association; professional membership; professional society; Program Development; Public Health; Questionnaires; Relapse; Research Design; Study Type; study design; Research Personnel; Investigators; Researchers; Safety; Saliva; Ships; Smoking; Testing; Time; Treatment Protocols; Treatment Regimen; Treatment Schedule; Vendor; cytisine; citizine; cystisin; cytiton; Accountability; Measures; smoking cessation; cease smoking; quit smoking; stop smoking; Schedule; Withdrawal Symptom; Label; Procedures; Site; Clinical; Phase; Biochemical; Medical; Safety Management; Individual; Databases; Data Bases; data base; Licensing; Logistics; Measurement; uptake; Agonist; Contracting Opportunities; Contracts; Cigarette Smoker; programs; Severities; Salivary; Protocol; Protocols documentation; Treatment Period; treatment days; treatment duration; System; Visit; data management; success; Agreement; Self-Report; Patient Self-Report; disease risk; disorder risk; Devices; Intervention Strategies; interventional strategy; Intervention; Molecular Interaction; Binding; Patient Compliance; patient adherence; patient cooperation; therapy compliance; therapy cooperation; treatment compliance; compliance behavior; Dose; High Prevalence; randomisation; randomization; randomly assigned; Randomized; Subgroup; Case Report Form; Enrollment; enroll; Smoking History; pack years; Monitor; Characteristics; Development; developmental; Behavioral; next generation; efficacy evaluation; efficacy analysis; efficacy assessment; efficacy examination; evaluate efficacy; examine efficacy; clinical research site; clinical site; Outcome; 18 year old; 18 years of age; age 18 years; eighteen year old; eighteen years of age; Abstinence; treatment effect; demographics; commercialization; FDA approved; group intervention; Biological Markers; bio-markers; biologic marker; biomarker; smoking relapse; public health priorities; arm; Institutional Review Boards; IRB; IRBs; Adolescent and Young Adult; Electronic cigarette; e-cig; e-cigarette; ecig; ecigarette; Pulmonary Inflammation; Pneumonitis; vaping; Electronic Nicotine Delivery Systems; Electronic Nicotine Delivery Product; electronic nicotine delivery device; electronic nicotine distribution system; clinical development; nicotine use; nicotine consumption; electronic cigarette user; e-cig user; e-cigarette user; ecig user; ecigarette user; vaper; nicotine exposure; exposure to nicotine; electronic cigarette use; e-cig use; e-cigarette use; ecig use; ecigarette use; nicotine cessation; Lung infections; pulmonary infections; Infrastructure; side effect; e-cigarette cessation; e-cig cessation; ecig cessation; quitting e-cigarettes; quitting e-cigs; quitting ecigarettes; quitting ecigs; vaping nicotine; efficacy outcomes; nicotine reward
