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

Phase 2

Recruiting

• Conditions: Smoking Cessation; Tobacco Use Disorder
• Interventions: Drug: Cytisinicline; Drug: Placebo Oral Capsule

• Registration Number: NCT06617312
• Lead Sponsor: University of California, Los Angeles

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.

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 Timeline

• Study First Submitted: 2024-09-24
• Study First Submitted QC: 2024-09-24
• Study First Posted: 2024-09-27
• Status Verified: 2024-11
• Last Update Submitted: 2024-11-22
• Last Update Posted: 2024-11-26
• Study Start: 2025-01
• Primary Completion: 2026-12
• Study Completion: 2026-12

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 64

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 in 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 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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Cytisinicline	Cytisinicline	3mg cytisinicline oral capsule 3 times daily for 2-to-3 weeks
Placebo	Placebo Oral Capsule	matched to experimental drug

Primary Outcome Measures

Name	Time	Method
Blood-oxygen-level-dependent (BOLD) activation to cigarette cues during fMRI task	From enrollment to end of treatment at 2-to-3 weeks	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.

Secondary Outcome Measures

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

Trial Locations

Locations (1)

University of California Los Angeles; 🇺🇸 Los Angeles, California, United States