Examining the Effects of Cytisinicline on Neural Substrates of Cigarette Cue-reactivity

NCT06617312 | Recruiting Phase 2 FDA Drug

• 2 other identifiers: 24-001071T34FT8089
• Study Type: interventional
• Target: 64
• Locations: 1 country
• Sites: 1

Brief Summary

This study will randomize 64 non-treatment seeking individuals who smoke cigarettes daily in a double-blind, placebo-controlled laboratory study testing the effects of cytisinicline on the neural substrates of cigarette cue reactivity.

Conditions

Tobacco Use Disorder; Smoking Cessation

Keywords

smoking cesstion; tobacco use disorder; cigarette smoking; fMRI; cytisinicline

Outcome Measures

Primary Outcomes (1)

• Blood-oxygen-level-dependent (BOLD) activation to cigarette cues during fMRI task

  Participants will complete a cigarette cue-exposure task during fMRI. In this paradigm, participants are exposed to videotaped cues of smoking and control, non-cigarette related, content. Blood-oxygen-level-dependent (BOLD) activation to cigarette (vs. non-cigarette control ) cues will be calculated.

  From enrollment to end of treatment at 2-to-3 weeks

Secondary Outcomes (2)

• In-scanner cigarette cue-induced subjective craving

  From enrollment to end of treatment at 2-to-3 weeks

• Subjective cigarette craving during outpatient period

  From enrollment to end of treatment at 2-to-3 weeks

Study Arms (2)

Cytisinicline

EXPERIMENTAL

3mg cytisinicline oral capsule 3 times daily for 2-to-3 weeks

Drug: Cytisinicline

Placebo

PLACEBO COMPARATOR

matched to experimental drug

Drug: Placebo Oral Capsule

Interventions

Cytisinicline DRUG

Targets α4β2 nicotinic acetylcholine receptors

Cytisinicline

Placebo Oral Capsule DRUG

Matched to active drug, cytisinicline

Placebo

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• be between the ages of 18 and 65 and provide informed consent;
• smoke 5 or more combustible cigarettes per day;
• not seeking treatment for smoking;

You may not qualify if:

• current use of other smoking cessation aid (bupropion, varenicline, nortriptyline, NRT);
• more than 3 months of smoking abstinence in past year;
• use of non-cigarette tobacco product (pipe tobacco, cigars, smokeless tobacco, hookah) or electronic cigarettes more than 5 times in the 28-days prior to enrollment;
• current use of psychoactive drug (excluding cannabis), as determined by urine toxicology;
• current (past 12-month) DSM-5 diagnosis of substance use disorder for any substances other than tobacco and mild cannabis or mild-to-moderate alcohol use disorders;
• lifetime history of psychotic disorders, bipolar disorders, or major depression with suicidal ideation;
• current suicidal ideation or lifetime history of suicide attempt;
• serious medical illness within past 3 months, including recent history of acute myocardial infarction, unstable angina, stroke, cerebrovascular incident, or hospitalization for congestive heart failure;
• medical condition that may interfere with safe study participation;
• renal impairment defined as a creatinine clearance (CrCl) greater than 60 mL/min (estimated with the Cockroft-Gault equation);
• exceed Grade 2 laboratory abnormalities, based on FDA Guidance Document "Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials";
• uncontrolled hypertension (blood pressure ≥160/100 mmHg);
• abnormal electrocardiogram;
• non-removable ferromagnetic object in body;
• claustrophobia;

Sponsors & Collaborators

• University of California, Los Angeles: lead

Study Sites (1)

University of California Los Angeles

Los Angeles, California, 90049, United States

RECRUITING

MeSH Terms

Conditions

Smoking Cessation; Tobacco Use Disorder; Cigarette Smoking

Interventions

cytisine

Condition Hierarchy (Ancestors)

Health Behavior; Behavior; Substance-Related Disorders; Chemically-Induced Disorders; Mental Disorders; Tobacco Smoking; Smoking; Tobacco Use

Central Study Contacts

Dylan E Kirsch, PhD

CONTACT

(310) 206-6756; dylankirsch@psych.ucla.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Model Details: We will randomize 64 non-treatment seeking adults who smoke cigarettes (N=32 cytisinicline, N=32 placebo; 50% females) in a double-blind, placebo-controlled laboratory study testing the effects of cytisinicline on the neural substrates of cigarette cue reactivity. All participants will be daily combustible cigarette smokers. Interested individuals will call the lab and complete a telephone screening interview. Individuals who are deemed eligible will receive a full explanation of study procedures and provide written, informed consent. Participants will then complete a behavioral screen and physical exam. Eligible participants will then be randomized to a medication, cytisinicline (3 mg, 3 times daily) or placebo (0mg, 3 times daily). Participants will complete brief daily diary self-reports of cigarette use and craving during the outpatient medication period. Following 2- to 3-weeks of cytisinicline, or placebo, treatment participants will complete a cigarette cue-exposure fMRI task.

Study Record Dates

• First Submitted: September 24, 2024
• First Posted: September 27, 2024
• Study Start: December 5, 2024
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2026
• Last Updated: December 3, 2025

Record last verified: 2025-11

Locations

US (1)