Nicotine DependencePhase 1NCT03999099
Targeting Orexin to Treat Nicotine Dependence
A Phase 1 study testing Suvorexant 20 mg and Suvorexant 10 mg in people with Nicotine Dependence, run by Mclean Hospital at 1 site in United States.
Trial summary
Tobacco smoking continues to be the primary cause of preventable mortality in the United States. Despite the availability of smoking cessation aids, the majority of those trying to quit smoking end up relapsing. Read more about this study
- Who is it for?
- Ages 18 to 50 years
- Conditions the study is for
- Nicotine Dependence
- What is being tested?
- Suvorexant 20 mg and Suvorexant 10 mg
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 4 participants
- Where
- 1 siteUnited States
- Study dates
- 26 Sep 2019to 31 Jul 2023
- Phase
- Phase 1
- Are there results?
- None posted in the registry
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 50 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- Participants will be male and female volunteers between the ages of 18-50
- Participants must report daily smoking of at least 5 cigarettes per day over the last 6 months.
- Participants must be nicotine dependent, having an FTND score greater than or equal to 4.
- Participants must have an expired carbon monoxide level of 10 ppm or more on the screening day.
- Participants must have an expired carbon monoxide level of no more than 10 ppm on the study visits.
- Female participants must have a negative pregnancy test on all study days.
Who cannot join
- Participants cannot meet DSM-5 criteria for lifetime and/or current psychotic disorders such as bipolar disorder, schizophrenia, schizoaffective disorder
- Participants cannot meet DSM-5 criteria for current substance abuse disorders other than nicotine and marihuana and cannot meet criteria for current moderate or severe alcohol use disorder (as assessed by the SCID-5)
- Participants cannot have positive drug and alcohol screen on each study visit other than for nicotine or marijuana.
- Participants reporting marihuana use greater than 1-2 times per week will be excluded.
- Participants must report no marihuana use within 24 hours of the study visit.
- Participants cannot be taking any prescription medication that could impact brain function including medications that depress CNS function
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- Participants cannot have a history of major head trauma resulting in cognitive impairment, seizure, or other neurological disorders.
- Participants cannot be pregnant or breastfeeding.
- Participants must be able to read screening materials including consent form and give informed consent
- Individuals with severe hepatic impairment will be excluded.
- Participants cannot be obese as determined by a Body Mass Index (BMI) of 30 or greater.
- Participants cannot be using a CYP3A inhibitor/inducer (metabolism by CYP3A is the major elimination pathway for suvorexant)
- Participants cannot have a current cardiac disorder such as palpitations, tachycardia and/or use of the cardiac medication Digoxin
- Participants cannot have narcolepsy
- Participants cannot self-report complex sleep behaviors such as sleep driving, preparing and eating food or making phone calls
- Participants cannot have compromised respiratory function such severe obstructive sleep apnea or severe chronic obstructive pulmonary disease
- Participants cannot have current major depressive disorder (within the past 6 months) and/or indorse suicidal ideation on the Beck Depression Inventory.
Trial locations and contacts
1 site in 1 country.
About this study
Tobacco smoking continues to be the primary cause of preventable mortality in the United States. Despite the availability of smoking cessation aids, the majority of those trying to quit smoking end up relapsing. Thus, there is a strong need to evaluate alternative treatment targets such as orexin antagonists, which have shown promise in preclinical models at reducing the motivational aspects of drug use.The current work will evaluate the influence of orexin antagonism on several factors impacting the motivation to smoke.
Read the detailed description
Tobacco use leads to ~440,000 deaths and a loss of $193 billion every year in the US. This public health and economic crisis continues as no interventions effectively prevent smoking relapse. Between 40-70% of smokers are unable to maintain abstinence and 75% of those who do attain abstinence will relapse within one-year. These relapse rates remain high even when using currently available cessation aids, which primarily target the cholinergic system, suggesting the need for medications with novel targets such as orexin. The current proposal will improve scientific knowledge and/or clinical practice by translating preclinical research on orexin into the clinical domain by indicating: 1) whether orexin antagonism attenuates motivational factors associated with smoking relapse, 2) whether suvorexant shows promise as a smoking cessation aid, or 3) whether suvorexant contributes too many unwanted side effects despite mitigating the motivation to smoke, thus confirming the role of orexin in nicotine dependence and indicating the need to develop more specific orexin antagonists.
- Conditions
- Nicotine Dependence
- Being tested
- Suvorexant 20 mg, Suvorexant 10 mg, Placebo oral tablet
- Medical subject headings
- Tobacco Use Disorder
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Suvorexant 20 mgDrug
Suvorexant at a high dose (20 mg)
Suvorexant 10 mgDrug
Suvorexant at a low dose (10 mg)
Placebo oral tabletDrug
Placebo
| Study group | Role | What they receive |
|---|---|---|
| Placebo | Placebo comparator | Not described Receives: Drug: Placebo oral tablet |
| Suvorexant 10mg | Experimental | Suvorexant 10mg oral dose Receives: Drug: Suvorexant 10 mg |
| Suvorexant 20mg | Experimental | Suvorexant 20mg oral dose Receives: Drug: Suvorexant 20 mg |
What is being measured
The primary outcome is the main question the study is designed to answer.
Nicotine Craving
Total average value on the Questionnaire of Smoking Urges (QSU): and average values for Factors 1 and 2
Measured: approximately 4 hours post drug administration and following exposure to visual smoking cues
Nicotine withdrawal
Wisconsin Smoking Withdrawal Scale: Total average value
Measured: approximately 4 hours post drug administration
Secondary outcomes (1)
Somnolence
Stanford Sleepiness Scale (SSS)
Measured: approximately 4 hours post drug administration
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Jun 2019
- Study start26 Sep 2019
- Primary completion31 Jul 2023
- Study completion31 Jul 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for Nicotine DependenceStudies of the same condition, open and under way.
- 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 1
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Model description
- A single group will undergo three study visits where, on different days, they will receive placebo, 10 mg, or 20 mg lorcaserin.
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 4 participants (actual)
Sponsor and investigators
- Lead sponsor
- Mclean Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Scott Lukas, Mclean Hospital
- Investigators
- Amy Janes, PhD, Principal investigator, Mclean Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03999099
- Sponsor's protocol ID
- Orexin and Nicotine
- Status last verified
- Sep 2026
- First submitted
- 16 Jun 2019
- Last updated
- 21 Sep 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Brandon TH, Tiffany ST, Obremski KM, Baker TB. Postcessation cigarette use: the process of relapse. Addict Behav. 1990;15(2):105-14. doi: 10.1016/0306-4603(90)90013-n.
PubMed 2343783Centers for Disease Control and Prevention (CDC). Smoking-attributable mortality, years of potential life lost, and productivity losses--United States, 2000-2004. MMWR Morb Mortal Wkly Rep. 2008 Nov 14;57(45):1226-8.
PubMed 19008791Hajek P, Stead LF, West R, Jarvis M, Lancaster T. Relapse prevention interventions for smoking cessation. Cochrane Database Syst Rev. 2009 Jan 21;(1):CD003999. doi: 10.1002/14651858.CD003999.pub3.
PubMed 19160228Hall SM, Humfleet GL, Reus VI, Munoz RF, Hartz DT, Maude-Griffin R. Psychological intervention and antidepressant treatment in smoking cessation. Arch Gen Psychiatry. 2002 Oct;59(10):930-6. doi: 10.1001/archpsyc.59.10.930.
PubMed 12365880Rohsenow DJ, Tidey JW, Martin RA, Colby SM, Swift RM, Leggio L, Monti PM. Varenicline versus nicotine patch with brief advice for smokers with substance use disorders with or without depression: effects on smoking, substance use and depressive symptoms. Addiction. 2017 Oct;112(10):1808-1820. doi: 10.1111/add.13861. Epub 2017 Jul 4.
PubMed 28498504
Study at a glance
From the registry record, last updated by the sponsor on 21 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Targeting Orexin to Treat Nicotine Dependence
- ClinicalTrials.gov ID
- NCT03999099
- Acronym / sponsor ID
- Orexin and Nicotine
- Conditions
- Nicotine Dependence
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 4 participants (actual)
- Lead sponsor
- Mclean HospitalUniversity, hospital or other
- Study start
- 26 Sep 2019 (actual)
- Primary completion
- 31 Jul 2023 (actual)
- Study completion
- 31 Jul 2023 (actual)
- First posted
- 26 Jun 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Tobacco smoking continues to be the primary cause of preventable mortality in the United States. Despite the availability of smoking cessation aids, the majority of those trying to quit smoking end up relapsing. Thus, there is a strong need to evaluate alternative treatment targets such as orexin antagonists, which have shown promise in preclinical models at reducing the motivational aspects of drug use.The current work will evaluate the influence of orexin antagonism on several factors impacting the motivation to smoke.
Detailed description
Tobacco use leads to ~440,000 deaths and a loss of $193 billion every year in the US. This public health and economic crisis continues as no interventions effectively prevent smoking relapse. Between 40-70% of smokers are unable to maintain abstinence and 75% of those who do attain abstinence will relapse within one-year. These relapse rates remain high even when using currently available cessation aids, which primarily target the cholinergic system, suggesting the need for medications with novel targets such as orexin. The current proposal will improve scientific knowledge and/or clinical practice by translating preclinical research on orexin into the clinical domain by indicating: 1) whether orexin antagonism attenuates motivational factors associated with smoking relapse, 2) whether suvorexant shows promise as a smoking cessation aid, or 3) whether suvorexant contributes too many unwanted side effects despite mitigating the motivation to smoke, thus confirming the role of orexin in nicotine dependence and indicating the need to develop more specific orexin antagonists.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 3
- Model description
- A single group will undergo three study visits where, on different days, they will receive placebo, 10 mg, or 20 mg lorcaserin.
| Arm | Type | Receives |
|---|---|---|
| Placebo | Placebo comparator | Drug: Placebo oral tablet |
| Suvorexant 10mg | Experimental | Drug: Suvorexant 10 mgSuvorexant 10mg oral dose |
| Suvorexant 20mg | Experimental | Drug: Suvorexant 20 mgSuvorexant 20mg oral dose |
Who may qualify
- Ages
- 18 to 50 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (6 listed)
- Participants will be male and female volunteers between the ages of 18-50
- Participants must report daily smoking of at least 5 cigarettes per day over the last 6 months.
- Participants must be nicotine dependent, having an FTND score greater than or equal to 4.
- Participants must have an expired carbon monoxide level of 10 ppm or more on the screening day.
- Participants must have an expired carbon monoxide level of no more than 10 ppm on the study visits.
Key exclusion criteria (17 listed)
- Participants cannot meet DSM-5 criteria for lifetime and/or current psychotic disorders such as bipolar disorder, schizophrenia, schizoaffective disorder
- Participants cannot meet DSM-5 criteria for current substance abuse disorders other than nicotine and marihuana and cannot meet criteria for current moderate or severe alcohol use disorder (as assessed by the SCID-5)
- Participants cannot have positive drug and alcohol screen on each study visit other than for nicotine or marijuana.
- Participants reporting marihuana use greater than 1-2 times per week will be excluded.
- Participants must report no marihuana use within 24 hours of the study visit.
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 |
|---|---|---|
| Suvorexant 20 mgSuvorexant at a high dose (20 mg) | Drug | Suvorexant 20mg |
| Suvorexant 10 mgSuvorexant at a low dose (10 mg) | Drug | Suvorexant 10mg |
| Placebo oral tabletPlacebo | Drug | Placebo |
Primary outcome
Nicotine Craving
Time frame: approximately 4 hours post drug administration and following exposure to visual smoking cues
Total average value on the Questionnaire of Smoking Urges (QSU): and average values for Factors 1 and 2
Nicotine withdrawal
Time frame: approximately 4 hours post drug administration
Wisconsin Smoking Withdrawal Scale: Total average value
1 secondary outcome
Somnolence
Time frame: approximately 4 hours post drug administration
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Sep 2026.
- Background: PubMed 2343783Brandon TH, Tiffany ST, Obremski KM, Baker TB. Postcessation cigarette use: the process of relapse. Addict Behav. 1990;15(2):105-14. doi: 10.1016/0306-4603(90)90013-n.
- Background: PubMed 19008791Centers for Disease Control and Prevention (CDC). Smoking-attributable mortality, years of potential life lost, and productivity losses--United States, 2000-2004. MMWR Morb Mortal Wkly Rep. 2008 Nov 14;57(45):1226-8.
- Background: PubMed 19160228Hajek P, Stead LF, West R, Jarvis M, Lancaster T. Relapse prevention interventions for smoking cessation. Cochrane Database Syst Rev. 2009 Jan 21;(1):CD003999. doi: 10.1002/14651858.CD003999.pub3.
- Background: PubMed 12365880Hall SM, Humfleet GL, Reus VI, Munoz RF, Hartz DT, Maude-Griffin R. Psychological intervention and antidepressant treatment in smoking cessation. Arch Gen Psychiatry. 2002 Oct;59(10):930-6. doi: 10.1001/archpsyc.59.10.930.
- Background: PubMed 28498504Rohsenow DJ, Tidey JW, Martin RA, Colby SM, Swift RM, Leggio L, Monti PM. Varenicline versus nicotine patch with brief advice for smokers with substance use disorders with or without depression: effects on smoking, substance use and depressive symptoms. Addiction. 2017 Oct;112(10):1808-1820. doi: 10.1111/add.13861. Epub 2017 Jul 4.
- Individual participant dataSharing planned: No
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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.
Amy Janes, PhD principal investigator
Mclean Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Suvorexant 20 mg and Suvorexant 10 mg in people with Nicotine Dependence, run by Mclean Hospital 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 6 inclusion and 17 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 21 Sep 2026. 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Nicotine Craving (time frame: approximately 4 hours post drug administration and following exposure to visual smoking cues). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03999099, which also lists 5 linked publications.
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 21 Sep 2026; AzTrials last refreshed its copy on 31 Oct 2026.