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

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

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.

Study Overview

• Status: Recruiting
• Conditions: Smoking Cessation; Tobacco Use Disorder
• Intervention / Treatment: Drug: Cytisinicline; Drug: Placebo Oral Capsule

Detailed Description

The objective of this study is to examine the effects of cytisinicline on neural substrates of cigarette cue-reactivity. We will randomize 64 adults who smoke cigarettes daily (N=32 cytisinicline, N=32 placebo; 50% female) into a double-blind, placebo-controlled laboratory study of cytisinicline. Specifically, participants will complete a 2- to 3-week outpatient protocol that includes taking cytisinicline (3 mg, 3 times daily) or matched placebo (0 mg, 3 times daily) and completing a brief daily diary assessment of cigarette use and craving. Following 2- to 3-weeks of cytisinicline (or placebo) treatment, participants will complete a cigarette cue-exposure task during fMRI. Total study participation will be approximately 4 weeks.

• Study Type: Interventional
• Enrollment (Estimated): 64
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Dylan E Kirsch, PhD; Phone Number: (310) 206-6756; Email: dylankirsch@psych.ucla.edu

Study Locations

• United States
  • California
    • Los Angeles, California, United States, 90049
      • Recruiting
      • University of California Los Angeles
      • Contact: Dylan E Kirsch, PhD; Phone Number: 310-206-6756; Email: dylankirsch@psych.ucla.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

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

Exclusion Criteria:

1. current use of other smoking cessation aid (bupropion, varenicline, nortriptyline, NRT);
2. more than 3 months of smoking abstinence in past year;
3. 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;
4. current use of psychoactive drug (excluding cannabis), as determined by urine toxicology;
5. 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;
6. lifetime history of psychotic disorders, bipolar disorders, or major depression with suicidal ideation;
7. current suicidal ideation or lifetime history of suicide attempt;
8. 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;
9. medical condition that may interfere with safe study participation;
10. renal impairment defined as a creatinine clearance (CrCl) greater than 60 mL/min (estimated with the Cockroft-Gault equation);
11. 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";
12. uncontrolled hypertension (blood pressure ≥160/100 mmHg);
13. abnormal electrocardiogram;
14. non-removable ferromagnetic object in body;
15. claustrophobia;
16. serious head injury or period of unconsciousness (more than 30 minutes);
17. more than 250lbs;

18. Be pregnant, nursing, or planning to become pregnant while taking part in the study; and must agree to one of the following methods of birth control (if female), unless she or partner are surgically sterile:

    • Oral contraceptives
    • Contraceptive sponge
    • Patch
    • Double barrier
    • Intrauterine contraceptive device
    • Etonogestrel implant
    • Medroxyprogesterone acetate contraceptive injection
    • Hormonal vaginal contraceptive ring
    • Complete abstinence from sexual intercourse;
19. have experienced adverse effects to varenicline;
20. have an intense fear of needles or have had an adverse reaction to needle puncture.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cytisinicline; 3mg cytisinicline oral capsule 3 times daily for 2-to-3 weeks	Drug: Cytisinicline; Targets α4β2 nicotinic acetylcholine receptors
Placebo Comparator: Placebo; matched to experimental drug	Drug: Placebo Oral Capsule; Matched to active drug, cytisinicline

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
In-scanner cigarette cue-induced subjective craving	In-scanner cigarette cue-induced subjective craving ratings will be obtained following each cue exposure during the fMRI task.	From enrollment to end of treatment at 2-to-3 weeks
Subjective cigarette craving during outpatient period	Subjective cigarette craving, as assessed via daily diary self-report assessments, during the outpatient medication period	From enrollment to end of treatment at 2-to-3 weeks

Collaborators and Investigators

• Sponsor: University of California, Los Angeles

Study record dates

Study Major Dates

• Study Start (Actual): December 5, 2024
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2026

Study Registration Dates

• First Submitted: September 24, 2024
• First Submitted That Met QC Criteria: September 24, 2024
• First Posted (Actual): September 27, 2024

Study Record Updates

• Last Update Posted (Estimated): December 3, 2025
• Last Update Submitted That Met QC Criteria: November 25, 2025
• Last Verified: November 1, 2025

More Information

Terms related to this study

• Keywords: fMRI; tobacco use disorder; cigarette smoking; smoking cesstion; cytisinicline
• Additional Relevant MeSH Terms: Mental Disorders; Substance-Related Disorders; Chemically-Induced Disorders; Behavior; Smoking; Health Behavior; Tobacco Smoking; Tobacco Use; Tobacco Use Disorder; Smoking Cessation; Cigarette Smoking; cytisine
• Other Study ID Numbers: 24-001071; T34FT8089 (Other Identifier: Tobacco Related Disease Research Program)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No