Solriamfetol + CBT-I for Insomnia

Overseen By Michael Perlis, PHD

Age: 18 - 65

Sex: Any

Trial Phase: Phase 4

Sponsor: University of Pennsylvania

Must not be taking: Sleep aids, CNS active

Disqualifiers: Night shift, Renal issues, CAD, others

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 12 weeks

60 Participants Needed

Trial Summary

What is the purpose of this trial?

Medication is FDA approved. The objective of this project is to test the efficacy of solriamfetol for treating insomnia (alone and in combination with Cognitive Behavioral Therapy for Insomnia \[CBT-I\]). Ultimately, this study will test whether wake extension (regardless of how it is achieved) will consolidate sleep and improve sleep continuity.

Do I need to stop taking my current medications for the trial?

You will need to stop taking any medications that are used specifically to help you fall or stay asleep, such as trazodone, melatonin, or Tylenol PM. The trial does not specify other medication restrictions, but you should discuss your current medications with the trial team.

What data supports the effectiveness of the treatment Solriamfetol + CBT-I for Insomnia?

Research shows that Cognitive Behavioral Therapy for Insomnia (CBT-I) is effective in improving sleep and related outcomes in various populations, including cancer survivors and heart failure patients. It is considered the gold standard for treating insomnia, suggesting it could be beneficial when combined with other treatments like Solriamfetol. ^{1 2 3 4 5}

Is Solriamfetol safe for humans?

Solriamfetol has been studied for excessive daytime sleepiness in conditions like narcolepsy and obstructive sleep apnea. It is generally well tolerated, with common side effects including headache, nausea, decreased appetite, insomnia, and anxiety. Unlike some stimulants, it does not have cardiac effects or withdrawal issues. ^{6 7 8 9 10}

How is the drug Solriamfetol unique for treating insomnia?

Solriamfetol is unique because it is a selective dopamine and norepinephrine reuptake inhibitor, originally used to treat excessive daytime sleepiness in conditions like narcolepsy and obstructive sleep apnea. Unlike traditional insomnia treatments, it targets the brain's wakefulness-promoting pathways, potentially offering a novel approach when combined with cognitive behavioral therapy for insomnia (CBT-I). ^{6 9 11 12 13}

Eligibility Criteria

This trial is for adults with Insomnia Disorder as per DSM-5, experiencing specific sleep disturbances more than three nights a week for over six months. They must have daytime impairment and prefer to sleep between 10 PM and 8 AM. Excluded are pregnant or breastfeeding individuals, those with unstable health conditions, no internet access, night shift workers, renal issues, severe heart disease or hypertension, other sleep disorders, using certain medications or substances.

Inclusion Criteria

I often feel very tired or sleepy during the day.

Participants will meet the diagnostic criteria for Insomnia Disorder according to Diagnostic and Statistical Manual of Mental Disorders (DSM-5)

Must garner physician's assent from their primary care clinician

Exclusion Criteria

No access to computers, I-Pads, or the internet

I experience symptoms of sleep disorders other than insomnia.

Night shift work

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive solriamfetol and/or CBT-I for insomnia treatment

12 weeks

Regular visits as per study protocol

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Cognitive Behavioral Therapy for Insomnia (CBT-I)
• Monitoring
• Placebo
• Solriamfetol

Trial Overview The study tests the effectiveness of solriamfetol (a medication) alone and combined with Cognitive Behavioral Therapy for Insomnia (CBT-I). It aims to see if extending wakefulness can improve sleep quality. Participants will be monitored and may receive either the drug at a specified dose, CBT-I therapy sessions, placebo pills that contain no active drug or just monitoring without intervention.

Participant Groups

Group I: Solriamfetol+ CBT-I Experimental Treatment 2 Interventions

Group II: Solriamfetol Only Experimental Treatment 2 Interventions

Group III: Placebo + CBT-I Active Control 2 Interventions

Group IV: Placebo Only Placebo Group 2 Interventions

Solriamfetol is already approved in United States for the following indications:

Approved in United States as Sunosi for:

• Excessive daytime sleepiness in patients with narcolepsy
• Excessive daytime sleepiness in patients with obstructive sleep apnea

Who Is Running the Clinical Trial?

University of Pennsylvania

Lead Sponsor

Trials

2,118

Recruited

45,270,000+

Axsome Therapeutics, Inc.

Industry Sponsor

Trials

34

Recruited

11,600+

Findings from Research

Cognitive Behavioral Therapy for Insomnia (CBT-I) has been shown to significantly improve sleep quality and psychological outcomes in cancer patients and survivors, based on a review of 12 studies.

CBT-I not only enhances sleep but may also positively affect mood, fatigue, and overall quality of life, and it can be delivered through various methods to reach more patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sleeping well with cancer: a systematic review of cognitive behavioral therapy for insomnia in cancer patients. Garland, SN., Johnson, JA., Savard, J., et al.[2022]

Cognitive-behavioral therapy for insomnia (CBT-I) has been proven effective in improving both short- and long-term outcomes for patients with uncomplicated and comorbid insomnia, indicating its strong efficacy as a treatment.

Future research on CBT-I should focus on enhancing treatment efficacy for clinically relevant outcomes, improving its effectiveness in community settings, and expanding training for practitioners to better disseminate the therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The future of cognitive behavioral therapy for insomnia: what important research remains to be done? Vitiello, MV., McCurry, SM., Rybarczyk, BD.[2018]

Cognitive behavioral therapy for insomnia (CBT-I) significantly improves sleep-related cognitions and insomnia severity in chronic heart failure patients, as shown in a study of 51 participants, with effects sustained for six months.

Changes in dysfunctional sleep-related beliefs were found to mediate the improvements in sleep quality and reductions in fatigue, depression, and anxiety, highlighting the importance of addressing these cognitions in treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of Cognitive Behavioral Therapy for Insomnia on Sleep-Related Cognitions Among Patients With Stable Heart Failure. Redeker, NS., Jeon, S., Andrews, L., et al.[2020]

A 6-week randomized controlled trial will assess the effectiveness of voice-activated cognitive behavioral therapy for insomnia (CBT-I) in breast cancer survivors, who often experience insomnia at rates of 30-50%.

The study aims to compare the efficacy of this innovative delivery method against a sleep education control, with the primary outcome being the Insomnia Severity Index score, which will help determine if this approach can effectively reduce insomnia symptoms in this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Testing delivery of components of cognitive behavioral therapy for insomnia to breast cancer survivors by smart speaker: a study protocol. Starling, CM., Greenberg, D., Zhou, E., et al.[2022]

A pilot study involving 30 Spanish-speaking breast cancer survivors showed that a 6-week eHealth Cognitive-Behavioral Therapy for Insomnia (CBT-I) intervention was highly acceptable and feasible, with excellent recruitment (95%) and retention (97%).

Post-treatment results indicated that CBT-I significantly improved insomnia symptoms, sleep disturbance, and sleep efficiency, with medium to large effect sizes, demonstrating its preliminary efficacy for this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pilot randomized controlled trial of eHealth cognitive-behavioral therapy for insomnia among Spanish-speaking breast cancer survivors. Oswald, LB., Morales-Cruz, J., Eisel, SL., et al.[2023]

In a study involving 50 patients with obstructive sleep apnea (OSA), most physicians initiated solriamfetol at doses of 37.5 or 75 mg/day, with many patients adjusting to stable doses of 75 or 150 mg/day within a median of 14 days.

The primary reason for initiating solriamfetol was the need for better efficacy in managing excessive daytime sleepiness, and most patients (96%) remained stable on the medication at the time of data collection.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Solriamfetol Titration and AdministRaTion (START) in Patients with Obstructive Sleep Apnea: A Retrospective Chart Review and Hypothetical Patient Scenario. Singh, H., Hyman, D., Parks, GS., et al.[2022]

Solriamfetol has been shown to significantly improve wakefulness in patients with narcolepsy and obstructive sleep apnea, with improvements of 7.65 to 10.14 minutes in narcolepsy and 4.5 to 12.8 minutes in OSA compared to placebo, based on data from 6 clinical trials involving both phase II and phase III studies.

The medication has a favorable safety profile, with fewer adverse effects and a lower risk of drug interactions compared to other treatments for excessive daytime sleepiness, making it a viable option for patients with narcolepsy and OSA.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Solriamfetol for the Management of Excessive Daytime Sleepiness. Cuomo, MC., Sheehan, AH., Jordan, JK.[2022]

Solriamfetol treatment for excessive daytime sleepiness in narcolepsy and obstructive sleep apnea showed long-term efficacy, with significant improvements in sleepiness scores and global impressions over a maintenance phase of up to 50 weeks.

The safety profile of solriamfetol was consistent with previous studies, with common side effects including headache and nausea, and no new safety concerns identified, although 9.5% of participants withdrew due to treatment-emergent adverse events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term study of the safety and maintenance of efficacy of solriamfetol (JZP-110) in the treatment of excessive sleepiness in participants with narcolepsy or obstructive sleep apnea. Malhotra, A., Shapiro, C., Pepin, JL., et al.[2021]

Solriamfetol is a new drug being considered by the FDA to treat excessive sleepiness in patients with obstructive sleep apnea (OSA) and narcolepsy, showing promise as an effective adjunctive therapy based on results from three Phase 3 trials.

Unlike traditional stimulants, solriamfetol is well tolerated and does not cause adverse cardiac effects, rebound hypersomnia, or withdrawal symptoms, making it a safer alternative for managing sleepiness in OSA patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Solriamfetol for the treatment of daytime sleepiness in obstructive sleep apnea. Abad, VC., Guilleminault, C.[2020]

Solriamfetol is a new medication that effectively promotes wakefulness in adults with narcolepsy by selectively inhibiting the reuptake of dopamine and norepinephrine, as shown in clinical trials.

The drug was well tolerated by patients, with common side effects including headache, nausea, decreased appetite, insomnia, and anxiety, indicating a manageable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Solriamfetol for the treatment of excessive daytime sleepiness associated with narcolepsy. Yang, J., Gao, J.[2020]

Solriamfetol (Sunosi™) is a newly approved oral medication in the USA that acts as a selective dopamine and norepinephrine reuptake inhibitor, specifically targeting excessive daytime sleepiness linked to narcolepsy and obstructive sleep apnoea.

The drug works by influencing the regulation of sleep-wake cycles through the dopaminergic and norepinephrine systems, addressing the underlying dysregulation that causes excessive sleepiness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Solriamfetol: First Global Approval. Markham, A.[2020]

Solriamfetol significantly improves excessive sleepiness in adults with narcolepsy and obstructive sleep apnea, as evidenced by increased mean sleep latency and reduced Epworth Sleepiness Scale scores in a meta-analysis of 1177 patients from five randomized controlled trials.

While solriamfetol is effective, it is associated with a higher risk of adverse events compared to placebo, although the risk of serious adverse events is not significantly different between the two groups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of solriamfetol for excessive sleepiness in narcolepsy and obstructive sleep apnea: findings from randomized controlled trials. Wang, J., Yang, S., Li, X., et al.[2021]

In a posthoc analysis of two 12-week phase 3 studies involving 690 participants with narcolepsy or obstructive sleep apnea, solriamfetol significantly reduced excessive daytime sleepiness, with 30.5%-73.0% of participants achieving normal Epworth Sleepiness Scale scores (≤ 10) compared to placebo.

The safety profile of solriamfetol was similar for both narcolepsy and obstructive sleep apnea patients, with common side effects including headache and nausea, indicating it is a well-tolerated treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinically relevant effects of solriamfetol on excessive daytime sleepiness: a posthoc analysis of the magnitude of change in clinical trials in adults with narcolepsy or obstructive sleep apnea. Rosenberg, R., Baladi, M., Bron, M.[2022]

References

1. New Zealand pubmed.ncbi.nlm.nih.gov

Sleeping well with cancer: a systematic review of cognitive behavioral therapy for insomnia in cancer patients. [2022]

2. United States pubmed.ncbi.nlm.nih.gov

The future of cognitive behavioral therapy for insomnia: what important research remains to be done? [2018]

3. England pubmed.ncbi.nlm.nih.gov

Effects of Cognitive Behavioral Therapy for Insomnia on Sleep-Related Cognitions Among Patients With Stable Heart Failure. [2020]

4. England pubmed.ncbi.nlm.nih.gov

Testing delivery of components of cognitive behavioral therapy for insomnia to breast cancer survivors by smart speaker: a study protocol. [2022]

5. United States pubmed.ncbi.nlm.nih.gov

Pilot randomized controlled trial of eHealth cognitive-behavioral therapy for insomnia among Spanish-speaking breast cancer survivors. [2023]

6. United States pubmed.ncbi.nlm.nih.gov

Solriamfetol Titration and AdministRaTion (START) in Patients with Obstructive Sleep Apnea: A Retrospective Chart Review and Hypothetical Patient Scenario. [2022]

7. United States pubmed.ncbi.nlm.nih.gov

Solriamfetol for the Management of Excessive Daytime Sleepiness. [2022]

8. United States pubmed.ncbi.nlm.nih.gov

Long-term study of the safety and maintenance of efficacy of solriamfetol (JZP-110) in the treatment of excessive sleepiness in participants with narcolepsy or obstructive sleep apnea. [2021]

9. England pubmed.ncbi.nlm.nih.gov

Solriamfetol for the treatment of daytime sleepiness in obstructive sleep apnea. [2020]

10. England pubmed.ncbi.nlm.nih.gov

Solriamfetol for the treatment of excessive daytime sleepiness associated with narcolepsy. [2020]

11. New Zealand pubmed.ncbi.nlm.nih.gov

Solriamfetol: First Global Approval. [2020]

12. Netherlands pubmed.ncbi.nlm.nih.gov

Efficacy and safety of solriamfetol for excessive sleepiness in narcolepsy and obstructive sleep apnea: findings from randomized controlled trials. [2021]

13. United States pubmed.ncbi.nlm.nih.gov

Clinically relevant effects of solriamfetol on excessive daytime sleepiness: a posthoc analysis of the magnitude of change in clinical trials in adults with narcolepsy or obstructive sleep apnea. [2022]