Neural Mechanisms Connecting Deficient Sleep and Smoking Relapse

The study aims to investigate whether behavioral interventions promote cessation in adult smokers by ameliorating negative emotions and improving self-control and identify the neural markers of these effects.

Study Overview

• Status: Recruiting
• Conditions: Insomnia; Tobacco Cessation; Tobacco Use
• Intervention / Treatment: Behavioral: Experimental health intervention; Drug: Varenicline

Detailed Description

The primary objectives of this study are to compare the effectiveness of two types of behavioral interventions, when combined with varenicline medication, in promoting tobacco cessation among treatment-seeking adults and to elucidate the underlying mechanisms. The secondary objective of this study is to examine sex differences.

Investigators will recruit from two primary sources: 1) community-based recruitment strategies including web and social media ads, lay community members to recruit, and local communication channels; 2) investigators will invite referred patients to the outpatient Tobacco Treatment Service (TTS) at Yale-New Haven Hospital.

All participants will be assigned to one of two behavioral interventions. Both groups will receive treatment with varenicline and attend weekly individual counseling sessions (standard care or cognitive behavioral therapy for insomnia) and wear research-grade sleep actiwatches for passive sleep monitoring.

Participants will have a total of five expected research visits with a scheduled target quit date for Week 4. Participants will undergo MRI at baseline and at Week 4, and attend follow-ups at week 8, 12, and 26.

• Study Type: Interventional
• Enrollment (Estimated): 114
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Lisa Fucito, PhD; Phone Number: 203-200-1470; Email: lisa.fucito@yale.edu
• Study Contact Backup: Name: Yu Chen, PhD; Phone Number: 347-819-2969; Email: yu.chen.yc838@yale.edu

Study Locations

• United States
  • Connecticut
    • New Haven, Connecticut, United States, 06520
      • Recruiting
      • Yale University
      • Contact: Yu Chen, PhD; Phone Number: 475-261-6153; Email: sleepstudy@yale.edu
    • New Haven, Connecticut, United States, 06519
      • Recruiting
      • Connecticut Mental Health Center
      • Contact: Yu Chen, PhD; Phone Number: 475-261-6153; Email: sleepstudy@yale.edu

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• English literate
• report heavy tobacco use (including nicotine e-cigarettes) for >6 months
• meet biochemical cut off for recent cigarette smoking or e-cigarette use
• optimal body mass index

Exclusion Criteria:

• currently enrolled in other treatments
• neuropsychiatric exclusions that could interfere with study participation, increase risk of adverse events, and/or induce deficient sleep
• medical contraindications for fMRI, varenicline, and/or behavioral treatment
• factors that cause deficient sleep and for which behavioral treatment has less benefit
• women who are pregnant or nursing

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Experimental health intervention; Experimental health intervention and varenicline starting 4 weeks before and continuing for 4 weeks after a target quit date for a total of 8 weeks	Behavioral: Experimental health intervention; Behavioral health intervention; Drug: Varenicline; Days 1-3: 0.5mg once daily, Days 4-7: 0.5mg twice daily; Days 8-56: 1.0mg twice daily.
Active Comparator: Control health intervention; Control health intervention and varenicline starting 4 weeks before and continuing for 4 weeks after a target quit date for a total of 8 weeks	Drug: Varenicline; Days 1-3: 0.5mg once daily, Days 4-7: 0.5mg twice daily; Days 8-56: 1.0mg twice daily.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean number cigarettes smoked per day	Mean number cigarettes smoked per day assessed by Time Line Follow Back method	Baseline, week 4, 8, 12, and 26
Smoking status	Assess expired breath carbon monoxide (CO) at baseline. CO is a standard biomarker of combustible tobacco use, is sensitive to detecting cigarette substitution, and has a typical half-life of 4 hours, and is a standard biomarker for confirming recent smoking abstinence (CO <5ppm has optimal sensitivity and specificity for biochemically verifying smoking status, including at lower smoking levels).	Baseline
Quit status	To inquire whether participants have refrained from tobacco use at each visit following their quit date. The quit status will also be verified by assessing expired breath carbon monoxide (CO). CO is a standard biomarker of combustible tobacco use, is sensitive to detecting cigarette substitution, and has a typical half-life of 4 hours, and is a standard biomarker for confirming recent smoking abstinence (CO <5ppm has optimal sensitivity and specificity for biochemically verifying smoking status, including at lower smoking levels)	Week 4, 8, 12, and 26
Days to smoking relapse	Days of resuming smoking since Week 4 schedule quit date as assessed by the Time Line Follow-back	Week 4, 8, 12, and 26

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in PROMIS Sleep Disturbance	The PROMIS Sleep Disturbance is an 8 item self-report of perceptions of sleep quality, sleep depth, and restoration associated with sleep. Each item on the measure is rated on a 5-point scale. PROMIS measures are scored on the T-score metric in which 50 is the mean of a relevant reference population and 10 is the standard deviation (SD) of that population. High scores mean greater severity of sleep disturbance.	Baseline, week 4, 8, 12, and 26
Change in PROMIS Sleep-Related Impairment	The PROMIS Sleep-Related Impairment is an 8 item self-report of perceptions of alertness, sleepiness, and tiredness during usual waking hours, and the perceived functional impairments during wakefulness. Each item on the measure is rated on a 4-point scale. The score range is 4 to 32. High scores mean greater severity of sleep related impairment.	Baseline, week 4, 8, 12, and 26
Change in Insomnia Severity Index	The Insomnia Severity Index is a 7-item brief screening tool for insomnia. Each item on the measure is rated on a 5-point scale (0-4), with a total score range 0-28. High scores mean greater severity of insomnia.	Baseline, week 4, 8, 12, and 26

Collaborators and Investigators

• Sponsor: Yale University
• Collaborators: National Institute on Drug Abuse (NIDA)
• Investigators: Principal Investigator: Lisa Fucito, PhD, Yale University; Principal Investigator: Chiang-Shan Li, Yale University

Study record dates

Study Major Dates

• Study Start (Actual): April 21, 2025
• Primary Completion (Estimated): June 1, 2029
• Study Completion (Estimated): June 1, 2029

Study Registration Dates

• First Submitted: September 20, 2024
• First Submitted That Met QC Criteria: September 20, 2024
• First Posted (Actual): September 24, 2024

Study Record Updates

• Last Update Posted (Actual): June 13, 2025
• Last Update Submitted That Met QC Criteria: June 11, 2025
• Last Verified: June 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Disease Attributes; Recurrence; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Neurotransmitter Agents; Cholinergic Agents; Nicotinic Agonists; Cholinergic Agonists; Varenicline
• Other Study ID Numbers: 2000037737; R01DA061285 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

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