Tobacco Use DisorderPhase 2RAPNCT02560324
Effect of Ramelteon on Smoking Abstinence
A Phase 2 study testing Ramelteon in people with Tobacco Use Disorder, run by University of Pennsylvania at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Tobacco Use Disorder
- What is being tested?
- Ramelteon
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 140 participants
- Where
- 1 siteUnited States
- Study dates
- Sep 2015to Aug 2018
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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).
Who cannot join
- 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.
Show all 43Show fewer
- 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):
- Current psychiatric disorders (depression, bipolar, schizophrenia, hypomanic/manic episode) as determined by self-report and/or MINI psychological interview.
- Past history of psychiatric disorders (including suicide attempt) other than depression as determined by self-report and/or MINI psychological interview.
- Suicide risk score on MINI greater than 1.
- Medical:
- Females who are currently pregnant, planning a pregnancy during the study, or currently breastfeeding/lactating. All female subjects shall undergo a urine pregnancy test at the Intake and must agree in writing to use an approved method of contraception. Following enrollment, pregnancy tests will be conducted at the beginning of each baseline week.
- For those with a history of jaundice/liver disease: liver function tests more than 20% outside of the normal range; Gamma-glutamyl Transpepsidase (GGT) values more than 20% outside of the normal range. If Albumin/Globulin ratios are 20% outside of normal range the abnormal value will be evaluated for clinical significance by the Study Physician and eligibility will determined on a case-by-case basis.
- Heart/Cardiovascular disease (e.g., angina, coronary heart disease, stroke, etc.) in the past 6 months.
- Endocrine or metabolic disorders (e.g., Type-I diabetes).
- Blood disorders (e.g., anemia or hemophilia).
- Uncontrolled hypertension (BP systolic greater than 159 and/or diastolic greater than 99)*.
- Clinically significant dyssomnia (except insomnia; e.g. sleep apnea syndrome, narcolepsy).
- Participants presenting with SBP greater than 159 mmHg and/or DBP greater than 99 mmHg at the Intake visit will be instructed to sit quietly for 10 minutes. Then the participant will have a second blood pressure reading taken after a 10 minute period. If, after the second reading the SBP greater than 159 mmHg and the DBP greater than 99 mmHg, the individual will be instructed to sit comfortably for 10 minutes and then have a third blood pressure reading. If, after the third reading the SBP greater than 159 mmHg and the DBP greater than 99 mmHg, the individual will be ineligible to participate.
- Medication:
- Current use or recent discontinuation (within the past month) of any of the following medications:
- Anti-anxiety or panic disorder medications (e.g., clonazepam, alprazolam).
- Anti-psychotic medications (e.g., thorazine, Seroquel).
- Mood-stabilizers (e.g., Lithium, Lamictal/lamotrigine, valproic acid, Neurontin/gabapentin, Topamax/topiramate, Tegretol/carbamazepine).
- Prescription stimulants (e.g., Provigil, Ritalin, Adderall).
- Medications contraindicated with ramelteon (e.g., fluvoxamine, buprenorphine or other medications metabolized by certain cytochrome P450 enzymes)
- Current use or recent discontinuation (within the past 2 weeks) of any of the following medications (subjects must agree to refrain from using any other sleep aids while enrolled in the study):
- Sleep medications (e.g., zolpidem/Ambien, eszopiclone/Lunesta)
- Over-the-counter sleep aids (e.g., melatonin, diphenhydramine/Benadryl)
- Daily use of opiate-containing medications for chronic pain (Duragesic/fentanyl patches, Percocet, Oxycontin). Smokers who report taking opiate-containing medications on an "as-needed" basis will be instructed to refrain from use until their study participation is over and that they will be tested to ensure they have complied with this requirement.
- Known allergy to study medication (e.g., angioedema).
- Subjects will be instructed to refrain from using any study prohibited drugs/medications (both recreational and prescription) throughout their participation in the study. After final eligibility is confirmed, subjects who report taking contraindicated medication(s) over the course of the study period may only remain eligible if the Study Physician and/or Principal Investigator determines that the contraindicated medication(s) do/did not impact the study design, data quality, and/or subject safety/welfare. Subjects are permitted to take necessary prescription medications not included within the exclusion list during the study.
- General Exclusion:
- Current, anticipated, or pending enrollment in another research program over the next 2-3 months that could potentially affect subject safety and/or the study data/design as determined by the Principal Investigator and/or Study Physician.
- Not planning to live in the area for the next two months.
- Currently working night shift or rotating shift or other habitual alteration of the sleep/wake cycle.
- Allergy to latex or adhesive tape.
- Inability to provide informed consent or complete any of the study tasks as determined by the Principal Investigator.
- Not able to effectively communicate in English (reading, writing, speaking).
- Missing 2 or more doses during the medication period determined by self-report.
Trial locations and contacts
1 site in 1 country.
United States1 site
Center for Interdisciplinary Research on Nicotine Addiction, School of Medicine, University of Pennsylvania
Philadelphia, Pennsylvania, 19104
About this study
Official title: Repurposing Melatonin Receptor Agonists as Adjunct Treatments for Smoking Cessation
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.
Read the 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.
- Conditions
- Tobacco Use Disorder
- Being tested
- Ramelteon, Placebo
- Keywords
- Ramelteon, Nicotine, Nicotine dependence, Insomnia, Tobacco Dependence
- Medical subject headings
- Tobacco Use Disorder, Sleep Initiation and Maintenance Disorders
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RamelteonDrug
PlaceboDrug
Also called Sugar Pill
| Study group | Role | What they receive |
|---|---|---|
| Ramelteon | Experimental | 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. Receives: Drug: Ramelteon |
| Placebo | Placebo comparator | 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. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Total Number of Smoke-free Days (Biochemically Verified) During Each 5-day Quit Assessment.
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.
Measured: Week 2 and Week 6
Secondary outcomes (3)
Subjective Sleep Disturbance
Sleep onset latency will be assessed via daily sleep diaries during each quit assessment.
Measured: Week 2 and Week 6
Objective Sleep Disturbance
Sleep efficiency (% of time in bed spent sleeping) will be assessed via the SensewearPro armbands during each quit assessment.
Measured: Week 2 and Week 6
Side Effects of Ramelteon
Side effects will be assessed at each in-person visit using a Side Effects Checklist (SEC) that lists 21 possible side effects of ramelteon. The scale for rating each side effect is None=0, Mild=1, Moderate=2, and Severe=3. The higher the score, the more side effects reported by the participant. The minimum score is 0 and the maximum score is 3 for each possible item on the scale. The Outcome Measure is an average of the 21 listed side effects.
Measured: Baseline (weeks 1 and 5); Quit assessments (weeks 2 and 6)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Sep 2015 (estimated)
- Study startSep 2015
- Primary completionAug 2018
- Study completionAug 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Tobacco Use DisorderStudies of the same condition, open and under way.
- More trials run by University of PennsylvaniaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 140 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Pennsylvania
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute on Drug Abuse (NIDA), National Institutes of Health (NIH)
- Responsible party
- Sponsor
- Investigators
- Rebecca Ashare, Ph.D., Principal investigator, University of Pennsylvania
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02560324
- Sponsor's protocol ID
- 823286
- Other IDs
- R21DA040902
- Acronym
- RAP
- Status last verified
- Nov 2019
- First submitted
- 23 Sep 2015
- Last updated
- 4 Nov 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 4 Nov 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Repurposing Melatonin Receptor Agonists as Adjunct Treatments for Smoking Cessation
- ClinicalTrials.gov ID
- NCT02560324
- Acronym / sponsor ID
- RAP / 823286
- Conditions
- Tobacco Use Disorder
- Keywords
- Ramelteon, Nicotine, Nicotine dependence, Insomnia, Tobacco Dependence
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 140 participants (actual)
- Lead sponsor
- University of PennsylvaniaUniversity, hospital or other
- Collaborators
- National Institute on Drug Abuse (NIDA), National Institutes of Health (NIH)
- Study start
- Sep 2015 (actual)
- Primary completion
- Aug 2018 (actual)
- Study completion
- Aug 2018 (actual)
- First posted
- 25 Sep 2015 (estimated)
- Results
- Posted 4 Nov 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Ramelteon | Experimental | Drug: RamelteonThe 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. |
| Placebo | Placebo comparator | Drug: Placebo5-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. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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).
Key exclusion criteria (43 listed)
- 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.
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Ramelteon | Drug | Ramelteon |
| PlaceboAlso: Sugar Pill | Drug | Placebo |
Primary outcome
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.
3 secondary outcomes
Subjective Sleep Disturbance
Time frame: Week 2 and Week 6
Objective Sleep Disturbance
Time frame: Week 2 and Week 6
Side Effects of Ramelteon
Time frame: Baseline (weeks 1 and 5); Quit assessments (weeks 2 and 6)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Nov 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Lung Health and Breath Biomarkers: Acute Effects of Inhaled Cannabis
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Young Adult Tobacco/Nicotine and Cannabis Co-use
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Rebecca Ashare, Ph.D. principal investigator
University of Pennsylvania
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Ramelteon in people with Tobacco Use Disorder, run by University of Pennsylvania at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 43 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 4 Nov 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 4 Nov 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Total Number of Smoke-free Days (Biochemically Verified) During Each 5-day Quit Assessment. (time frame: Week 2 and Week 6). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Nov 2019.