Belsomra + Methylphenidate for Smoking Cessation

Overseen By Amy C Janes, Ph.D.

Age: 18 - 65

Sex: Any

Trial Phase: Academic

Sponsor: National Institute on Drug Abuse (NIDA)

Must not be taking: CNS depressants, CYP3A inhibitors

Disqualifiers: Psychotic disorders, Neurological disorders, Obesity, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

Duration: 1-2 months

140 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new method to help people quit smoking by using suvorexant (Belsomra), a medication typically prescribed for insomnia, to see if it can alter brain functions linked to addiction. The study aims to determine if this drug can reduce the motivation to smoke and improve sleep in daily smokers. For non-smokers, the trial tests how suvorexant and methylphenidate (commonly used for ADHD) interact and affect brain functions related to reward and thinking. Individuals who have smoked or vaped daily for at least a year, or non-smokers interested in the cognitive effects of these drugs, might be suitable for this trial. As an unphased study, this trial offers a unique opportunity to contribute to groundbreaking research on addiction and cognitive function.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, if you are using medications that depress the central nervous system or are CYP3A inhibitors/inducers, you may be excluded from the study. It's best to discuss your current medications with the study team.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that suvorexant, also known as Belsomra, is generally safe to use. The FDA has approved it for treating insomnia, indicating it has undergone safety testing in people. Studies have found that suvorexant does not cause physical dependence, even with long-term use. However, some individuals might experience drowsiness, so avoiding activities like driving until its effects are known is important.

In this trial, researchers will study how suvorexant works when combined with methylphenidate. Methylphenidate is commonly used for attention issues, and its safety is well-established. Both treatments have been studied before, and no major safety concerns have been reported. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about combining Belsomra (suvorexant) with methylphenidate for smoking cessation because it offers a novel approach compared to current treatments like nicotine replacement therapies, bupropion, and varenicline. Unlike these standard options, suvorexant works by targeting the orexin system, which is involved in regulating wakefulness and has potential links to addictive behaviors. This unique mechanism could address nicotine dependence differently, potentially improving success rates for quitting smoking. Additionally, the combination with methylphenidate, a stimulant affecting dopamine levels, could further enhance the treatment's effectiveness by managing withdrawal symptoms and cravings.

What evidence suggests that this trial's treatments could be effective for smoking cessation?

Research has shown that suvorexant, a type of medication, might help reduce cravings and stress related to substance use. In studies, participants taking suvorexant during opioid withdrawal reported feeling less stressed than those who took a placebo. In this trial, participants in the Nicotine Dependence Arm will receive suvorexant to explore its potential to calm the brain's reward system, which often drives smoking and other habits. By blocking a brain chemical called orexin, the medication may reduce the urge to smoke. This suggests suvorexant might offer a new way to help people quit smoking. ^{3 4 6 7 8}

Who Is on the Research Team?

Amy C Janes, Ph.D.

Principal Investigator

National Institute on Drug Abuse (NIDA)

Are You a Good Fit for This Trial?

This trial is for daily smokers/vapers aged 18-60 who have been using nicotine consistently for at least a year. They must not use other drugs or alcohol, be pregnant, or have certain health conditions like severe heart disorders, respiratory issues, major depression (unless stable on medication), obesity with BMI over 35, or neurological disorders.

Inclusion Criteria

I can become pregnant and will take pregnancy tests on all study days.

I am willing to follow the study's lifestyle requirements and have given my written consent.

I have been smoking or vaping regularly for at least a year.

Exclusion Criteria

Participants cannot self-report complex sleep behaviors

I have never had a major head injury that affected my thinking, caused seizures, or led to other brain problems.

Participants cannot meet DSM-5 criteria for lifetime and/or current psychotic disorders such as bipolar disorder, schizophrenia, schizoaffective disorder or medical conditions that impact reward function

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive suvorexant and/or methylphenidate to assess neurobiological and behavioral impacts

1-2 months

Multiple visits for drug administration and fMRI scans

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Belsomra
• Placebo

Trial Overview The study tests the drug suvorexant's impact on brain function and behavior in people with nicotine addiction. It also examines how suvorexant interacts with methylphenidate in non-smokers. Participants will take a single dose of suvorexant and then daily doses for about a week; control subjects will receive various combinations of the drugs and placebo.

How Is the Trial Designed?

Group I: Nicotine Dependence Arm Experimental Treatment 2 Interventions

140 Volunteers who are between the ages of 18-60 and are daily smokers/vapers. Suvorexant at 10 mg single dose, and Suvorexant at 10 mg daily for approximately 7 days.

Group II: Control Arm Active Control 3 Interventions

80 Volunteers who are between the ages of 18-60 and are non-smokers/vapers. 1. Baseline visit with 1 fMRI scans pre- and post-20mg methylphenidate, 4 acute drug administration (6-14 days in randomized order: 1. Placebo + placebo; 2. 20mg suvorexant + Placebo; 3. Placebo + 40mg methylphenidate; 4. 20 mg suvorexant + 40mg methylphenidate max)

Belsomra is already approved in United States, European Union for the following indications:

Approved in United States as Belsomra for:

• Insomnia characterized by difficulties with sleep onset and/or sleep maintenance

Approved in European Union as Belsomra for:

• Insomnia characterized by difficulties with sleep onset and/or sleep maintenance

Who Is Running the Clinical Trial?

National Institute on Drug Abuse (NIDA)

Lead Sponsor

Trials

2,658

Recruited

3,409,000+

Published Research Related to This Trial

Bupropion sustained release (SR) significantly aids smoking cessation, with higher doses (100, 150, and 300 mg/day) increasing the likelihood of quitting by 1.42, 1.69, and 2.84 times, respectively, compared to placebo, based on a study of 519 chronic smokers.

The study found that side effects like insomnia and dry mouth were linked to bupropion metabolite concentrations, suggesting that managing these side effects through dose adjustments could impact smoking cessation success.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Relationship between drug exposure and the efficacy and safety of bupropion sustained release for smoking cessation. Johnston, JA., Fiedler-Kelly, J., Glover, ED., et al.[2023]

In a 9-week study involving 25 adults with depressive disorders, the addition of bupropion sustained release (SR) to their SSRI treatment resulted in a modest smoking cessation success rate, with 32% of participants abstinent at the end of the study.

Bupropion SR was found to be safe, as there were no new depressive episodes reported, minimal weight gain (approximately 0.5 lb), and some participants even experienced improvements in sexual dysfunction associated with SSRIs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bupropion sustained release as a smoking cessation treatment in remitted depressed patients maintained on treatment with selective serotonin reuptake inhibitor antidepressants. Chengappa, KN., Kambhampati, RK., Perkins, K., et al.[2022]

Varenicline is the most effective first-line pharmacotherapy for smoking cessation, showing a significant effect compared to placebo with an odds ratio of 2.27, followed by bupropion (1.69) and nicotine replacement therapy (1.60).

Despite some safety concerns, regulatory agencies deem bupropion and varenicline to have a favorable benefit/risk profile, but healthcare providers should monitor patients for potential neuropsychiatric symptoms, especially in those with psychiatric comorbidities.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacotherapy for smoking cessation: pharmacological principles and clinical practice. Aubin, HJ., Luquiens, A., Berlin, I.[2022]

Despite the availability of various smoking cessation pharmacotherapies, including nicotine replacement therapy and newer agents, less than 25% of smokers remain abstinent one year after treatment, highlighting the need for more effective options.

Combination therapies, particularly using nicotine replacement therapy alongside varenicline, have shown the highest rates of smoking cessation, while novel therapies like cytisine and N-acetylcysteine are emerging as promising alternatives.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Current and Emerging Pharmacotherapies for Cessation of Tobacco Smoking. Gómez-Coronado, N., Walker, AJ., Berk, M., et al.[2018]

Nicotine replacement therapies, including a new nicotine vapor inhaler and sublingual nicotine tablets, have shown effectiveness in treating nicotine dependence, with the vapor inhaler delivering nicotine to the oral mucosa and the sublingual tablet demonstrating efficacy in a placebo-controlled trial.

Combining pharmacotherapies, such as nicotine replacement with bupropion or mecamylamine, may enhance treatment outcomes by occupying more nicotine receptors, which could help reduce smoking rewards and support cessation efforts.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New medications for nicotine dependence treatment. Hurt, RD.[2019]

Citations

1. sigma.larvol.com sigma.larvol.com/product.php?e1=235628&tab=newstrac

Belsomra (suvorexant) News Individuals taking suvorexant during opioid withdrawal may experience decreased stress relative to placebo. Suvorexant may improve CRSD-related cognitive ...

2. withpower.com withpower.com/trial/phase-nicotine-dependence-11-2022-8b9f1

Belsomra + Methylphenidate for Smoking Cessation Varenicline is the most effective first-line pharmacotherapy for smoking cessation, showing a significant effect compared to placebo with an odds ratio of 2.27, ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10373598/

New medications development for smoking cessation - PMC Cytisine has shown mixed results in human clinical trials assessing its efficacy as a smoking cessation agent [55–57]. This likely reflects the fact that ...

4. tga.gov.au tga.gov.au/sites/default/files/auspar-suvorexant-150411.pdf

Australian Public Assessment Report for Suvorexant Taken together, the available nonclinical data present minimal/no convincing evidence for dependence potential with suvorexant. Confirmation ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT04234997

Suvorexant to Reduce Symptoms of Nicotine Use The purpose of this study is to assess the impact of suvorexant on established measures of smoking relapse risk (craving,withdrawal, stress reactivity, ...

6. mayoclinic.org mayoclinic.org/drugs-supplements/suvorexant-oral-route/description/drg-20113017

Suvorexant (oral route) - Side effects & dosage If too much is taken, it may become habit-forming (causing mental or physical dependence). This medicine should come with a Medication Guide.

7. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2018/204569s005lbl.pdf

This label may not be the latest approved by FDA. For current ... 9.3 Dependence​​ In completed clinical trials with BELSOMRA, there was no evidence for physical dependence with the prolonged use of BELSOMRA. There were no ...

8. nps.org.au nps.org.au/medicine-finder/belsomra-tablets

Belsomra Be careful driving, operating machinery or other activities that require complete alertness until you know how BELSOMRA affects you. As with other medicines ...