Repurposing Melatonin Receptor Agonists as Adjunct Treatments for Smoking Cessation
Overview
- Phase
- Phase 2
- Status
- Completed
- Sponsor
- University of Pennsylvania
- Enrollment
- 140
- Locations
- 1
- Primary Endpoint
- Total Number of Smoke-free Days (Biochemically Verified) During Each 5-day Quit Assessment.
Overview
Brief Summary
This is a randomized, double-blind, placebo-controlled crossover study to test whether a medication called ramelteon (Brand Name: Remeron) will help smokers quit and whether it reduces sleep problems that smokers experience during a quit attempt.
Detailed Description
Ramelteon, an FDA-approved treatment for insomnia, is used to treat sleep problems (e.g., specifically sleep onset latency) by enhancing melatonin receptor function. The investigators propose a randomized double-blind placebo-controlled crossover study.
Fifty chronic smokers will complete a validated procedure for screening new medications. All subjects will receive 8mg ramelteon and placebo. The order in which ramelteon and placebo is received will be randomized across participants. This is a 6-week study consisting of two 2-week medication phases separated by a 2-week washout. Each phase includes 1 week of ad libitum smoking (baseline) and 1 week of medication (ramelteon vs. placebo) plus transdermal nicotine patches while trying to abstain from smoking (quit assessment). Subjects will complete the same procedures during each study phase. Following completion of the study, participants will be offered standard smoking cessation treatment.
For the duration of the study, subjects will be asked to keep sleep diaries and to wear an armband while sleeping, which provides objective indices of sleep duration and quality (SensewearPro® armband).
The primary outcome will be the total number of days abstinent (out of 5) during each quit assessment period. Intermediate outcomes include sleep onset latency (self-report) and sleep efficiency (SensewearPro®).
This study will provide information about the role of the melatonin system during brief abstinence and whether enhancing melatonin reduces abstinence-induced sleep problems that promote smoking relapse. Information obtained in this study may further establish the role of sleep disturbance in promoting smoking relapse.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Crossover
- Primary Purpose
- Treatment
- Masking
- Triple (Participant, Care Provider, Investigator)
Eligibility Criteria
- Ages
- 18 Years to 65 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Smokers who are between 18 and 65 years of age who self-report smoking at least 10 cigarettes per day for at least the last 6 months.
- •Interest in quitting smoking in the next 2 to 4 months.
- •Healthy as determined by the Study Physician, based on a medical evaluation including medical history and physical examination, and psychiatric evaluation.
- •Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the combined consent and HIPAA form.
- •Women of childbearing potential must consent to use a medically accepted method of birth control while participating in the study (e.g., condoms and spermicide, oral contraceptive, Depo-provera injection, contraceptive patch, tubal ligation).
Exclusion Criteria
- •Smoking Behavior:
- •Current enrollment in a smoking cessation program, or use of other smoking cessation medications in the last month or plans to do either in the next 2 months.
- •Daily use of chewing tobacco, snuff and/or snus, or electronic cigarettes.
- •Provide a carbon monoxide (CO) breath sample reading less than 10 parts per million (ppm) at Intake.
- •Alcohol/Drugs:
- •Self-report current alcohol consumption that exceeds 25 standard drinks/week over the past 6 months. Subjects will be told to limit or avoid the use of alcohol while in the study to avoid any adverse reactions to the study medication.
- •Self-reports substance use disorders (abuse or dependence involving alcohol, opiates, cocaine or other stimulants, or benzodiazepines; not nicotine) in the last 6 months.
- •Providing a breath alcohol concentration (BrAC) reading of greater than or equal to 0.01 during any session.
- •A positive urine drug screen for cocaine, amphetamines, methamphetamines, benzodiazepines, PCP, methadone, barbiturates, marijuana, ecstasy (MDMA), oxycodone, tricyclic antidepressants, and opiates (low level cut-off 300 ng/mL) during any session.
- •Psychiatric Exclusion (as determined by self-report on phone screen and/or through MINI during Intake):
Arms & Interventions
Ramelteon
The study will be performed using 8mg of ramelteon, which is currently marketed for the treatment of sleep problems. The proposed study follows the typical dosing regimen for ramelteon (8mg once a day) for 5 days during each quit assessment period.
Ramelteon will be purchased and packaged into blister packs by the Investigational Drug Service (IDS) at the University of Pennsylvania. In accordance with FDA recommendations, subjects will be instructed to take study medication within 30 min prior to going to bed and avoid taking study medication with or immediately after a high fat meal.
Intervention: Ramelteon (Drug)
Placebo
5-day placebo-controlled medication period.
Placebo ingredients will be purchased, encapsulated, and packaged into blister packs by the IDS at UPenn. Both active medication and placebo will look identical.
The study medication assignments for each participant in this project is randomized and counterbalanced. This means that approximately 50% of participants will take ramelteon during the first medication period, followed by the placebo in the second medication period. Alternatively, approximately 50% of participants will take the placebo during the first medication period, followed by ramelteon during the second medication period.
Intervention: Placebo (Drug)
Outcomes
Primary Outcomes
Total Number of Smoke-free Days (Biochemically Verified) During Each 5-day Quit Assessment.
Time Frame: Week 2 and Week 6
The quit assessment will begin the Monday morning of each quit week and will end that Friday. The total number of days of abstinence will be assessed.
Secondary Outcomes
- Subjective Sleep Disturbance(Week 2 and Week 6)
- Objective Sleep Disturbance(Week 2 and Week 6)
- Side Effects of Ramelteon(Baseline (weeks 1 and 5); Quit assessments (weeks 2 and 6))