Modafinil + Solriamfetol for Excessive Daytime Sleepiness from Long COVID

Overseen By Barrie L Harper, BSMT (ASCP) PMP

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Duke University

Must not be taking: Stimulants, Hypnotics, MAOIs, Dopaminergics

Disqualifiers: Hypertension, Hepatic impairment, Heart problems, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 10 weeks

474 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests two drugs, Modafinil and Solriamfetol, to determine their effectiveness in alleviating excessive daytime sleepiness caused by Long COVID. Researchers aim to assess whether these medications can improve sleep-related issues such as hypersomnia (difficulty staying awake during the day) and other sleep disturbances. The trial includes different groups: some will receive the actual medication, while others will receive a placebo (a harmless pill with no effect). Suitable participants may have ongoing sleep problems from Long COVID but must not be using other stimulant medications or have certain heart or liver issues. As a Phase 2 trial, the research focuses on evaluating the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to significant findings.

Will I have to stop taking my current medications?

The trial may require you to stop taking certain medications. If you are currently using stimulant or wake-promoting medications, or prescribed hypnotics for sleep, a washout period (time without taking these medications) is permitted. Additionally, if you are taking medications that interact with Modafinil or Solriamfetol, you may need to modify or stop those medications.

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

Research has shown that both modafinil and solriamfetol are safe for treating excessive daytime sleepiness, particularly in conditions like narcolepsy and sleep apnea. The FDA has already approved modafinil for managing sleep disorders, and it has shown promise in alleviating fatigue and cognitive issues in individuals with long COVID.

Studies have found that solriamfetol is well-tolerated and can reduce daytime sleepiness and improve cognitive function. Both short- and long-term use of solriamfetol has been found to be safe, offering benefits for quality of life and work performance.

In summary, safety data supports the use of both modafinil and solriamfetol in similar conditions. They are generally well-tolerated and have a strong safety record. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about using Modafinil and Solriamfetol for treating excessive daytime sleepiness from long COVID because these medications target the condition by promoting wakefulness in a unique way. Both drugs work by influencing neurotransmitters in the brain, specifically dopamine and norepinephrine, which are known to play a significant role in regulating sleep and wake cycles. Unlike traditional treatments for sleepiness, which often focus on lifestyle changes or treating underlying sleep disorders, Modafinil and Solriamfetol offer a pharmacological approach that directly enhances alertness. This could potentially provide quicker and more effective relief for patients suffering from this challenging symptom of long COVID.

What evidence suggests that this trial's treatments could be effective for excessive daytime sleepiness from Long COVID?

Research shows that modafinil and solriamfetol are promising treatments for excessive daytime sleepiness, especially in conditions like narcolepsy and obstructive sleep apnea. The FDA has already approved modafinil for various sleep disorders, and it has proven effective in reducing daytime sleepiness. Studies have also found it useful for managing sleep problems after COVID-19. Solriamfetol significantly improves wakefulness, particularly in people with sleep disorders like narcolepsy. Both drugs alter brain chemicals to promote wakefulness and reduce sleepiness. In this trial, participants will receive either modafinil or solriamfetol, depending on their eligibility, to assess their effectiveness in managing sleep issues related to long COVID. ^{1 3 4 6 7}

Who Is on the Research Team?

Christina Barkauskas, MD

Principal Investigator

Duke Clinical Research Institute

Susan Redline, MD MPH

Principal Investigator

Brigham and Women's Hospital

Are You a Good Fit for This Trial?

This trial is for individuals experiencing excessive daytime sleepiness associated with COVID-19, known as Long COVID Syndrome or Post-COVID Syndrome. Participants should meet the general criteria outlined in the RECOVER-SLEEP platform protocol.

Inclusion Criteria

I meet the general requirements listed in the RECOVER-SLEEP study.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Baseline Assessment

Participants complete baseline assessments before randomization

1 week

Treatment

Participants receive either modafinil, solriamfetol, or placebo for 10 weeks

10 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Modafinil
• Solriamfetol

Trial Overview The trial is testing Modafinil and Solriamfetol against their respective placebos to see if they can improve sleep-related issues caused by PASC. It's a multi-center study where participants are randomly assigned to different treatment arms.

How Is the Trial Designed?

Group I: Wake-promoting drug: Modafinil or solriamfetol Active Control 2 Interventions

Participants in Appendix A will be randomized to study drug or control. Participants who meet the eligibility criteria for modafinil will receive either active modafinil or the modafinil-matched control. If modafinil is contraindicated for any reason, participants will be assessed for their ability to take solriamfetol. If participants are eligible for solriamfetol, they will receive either active solriamfetol or the solriamfetol-matched control. If solriamfetol is contraindicated, participants will be excluded from Appendix A. Modafinil and solriamfetol will be analyzed as a single wake-promoting drug condition versus control. The intervention duration will be 10 weeks.

Group II: Modafinil-matched placebo or solriamfetol-matched placebo Placebo Group 2 Interventions

Participants in Appendix A will be randomized to study drug or control. Participants who meet the eligibility criteria for modafinil will receive either active modafinil or the modafinil-matched control. If modafinil is contraindicated for any reason, participants will be assessed for their ability to take solriamfetol. If participants are eligible for solriamfetol, they will receive either active solriamfetol or the solriamfetol-matched control. If solriamfetol is contraindicated, participants will be excluded from Appendix A. Modafinil and solriamfetol will be analyzed as a single wake-promoting drug condition versus control. The intervention duration will be 10 weeks.

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

Approved in United States as Provigil for:

• Narcolepsy
• Shift Work Sleep Disorder
• Obstructive Sleep Apnea

Approved in European Union as Modafinil for:

• Excessive daytime sleepiness associated with narcolepsy
• Shift work sleep disorder
• Obstructive sleep apnea

Approved in Canada as Alertec for:

• Narcolepsy
• Shift Work Sleep Disorder
• Obstructive Sleep Apnea

Who Is Running the Clinical Trial?

Duke University

Lead Sponsor

Trials

2,495

Recruited

5,912,000+

Published Research Related to This Trial

In a study of 70 patients with excessive daytime sleepiness (EDS) due to narcolepsy, solriamfetol was commonly initiated at a dose of 75 mg/day, leading to significant improvements in EDS as measured by the Epworth Sleepiness Scale (ESS), with scores decreasing from 17.6 to 13.6 after treatment.

The majority of patients reported positive outcomes, with over 90% perceiving improvements in their EDS, and common side effects such as headache and decreased appetite were consistent with previous clinical trials, indicating a favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Solriamfetol real world experience study (SURWEY): Initiation, titration, safety, effectiveness, and experience during follow-up for patients with narcolepsy from Germany. Winter, Y., Mayer, G., Kotterba, S., et al.[2023]

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 significantly improved wakefulness in adults with excessive daytime sleepiness (EDS) associated with obstructive sleep apnea (OSA), showing effectiveness regardless of whether participants adhered to their primary OSA therapy.

The study, which included 459 participants over 12 weeks, found that solriamfetol did not affect the use of primary OSA therapy, indicating it can be safely used alongside existing treatments without altering their effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Randomized Controlled Trial of Solriamfetol for Excessive Daytime Sleepiness in OSA: An Analysis of Subgroups Adherent or Nonadherent to OSA Treatment. Schweitzer, PK., Mayer, G., Rosenberg, R., et al.[2021]

Modafinil, a central nervous system stimulant, shows potential for improving wakefulness in patients with traumatic brain injury (TBI), but evidence is mixed regarding its effectiveness for fatigue and excessive daytime sleepiness (EDS).

Among the studies reviewed, one randomized controlled trial found no significant improvement in wakefulness with modafinil, while another suggested it could correct EDS; further research is needed to clarify its benefits in TBI patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Modafinil for the Improvement of Patient Outcomes Following Traumatic Brain Injury. Borghol, A., Aucoin, M., Onor, I., et al.[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 significantly improves wakefulness in patients with excessive daytime sleepiness (EDS) due to narcolepsy or obstructive sleep apnea (OSA), showing a mean increase of nearly 10 minutes in the maintenance of wakefulness test compared to placebo.

The safety profile of solriamfetol is favorable, with common side effects including headache and nausea, but it remains well tolerated, making it a recommended treatment option for EDS in these patient populations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of solriamfetol for excessive daytime sleepiness in narcolepsy and obstructive sleep apnea: a systematic review and meta-analysis of clinical trials. Subedi, R., Singh, R., Thakur, RK., et al.[2021]

A study involving 1,096 patients examined the safety profile of modafinil in real-world clinical use, revealing that while most adverse drug reactions (ADRs) were previously documented, some serious events like psychosis were associated with higher doses.

The study highlighted a significant gap in contraceptive management, as many women of child-bearing potential were not on recommended contraceptive programs, leading to three pregnancies during modafinil treatment, emphasizing the need for effective contraceptive counseling for women taking this medication.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety profile of modafinil across a range of prescribing indications, including off-label use, in a primary care setting in England: results of a modified prescription-event monitoring study. Davies, M., Wilton, L., Shakir, S.[2021]

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]

Citations

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Modafinil: A Review and Its Potential Use in the Treatment ... Modafinil demonstrated a clear beneficial effect on excessive daytime sleepiness in patients with PD (mean difference in scores on the Epworth ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10899667/

Post-COVID central hypersomnia, a treatable trait in long COVID After the infection, he experienced excessive daytime sleepiness and a significant increase in his sleep requirements, up to 12–14 h per day.

3. onlinelibrary.wiley.com onlinelibrary.wiley.com/doi/abs/10.1002/npr2.12447

Evaluation of the effect of Modafinil in ... In a double-blinded trial in Tehran, modafinil showed potential for enhancing consciousness in COVID-19 patients with encephalopathy but ...

4. uchealth.com uchealth.com/en/media-room/articles/advancing-treatments-for-long-covid-sleep-disorders

Advancing Treatments for Long COVID Sleep Disorders These medications are wakefulness-promoting agents that help combat excessive daytime sleepiness by altering neurotransmitters in the brain ...

5. researchgate.net researchgate.net/publication/361591766_Modafinil_A_Review_and_Its_Potential_Use_in_the_Treatment_of_Long_COVID_Fatigue_and_Neurocognitive_Deficits

Modafinil: A Review and Its Potential Use in the Treatment ... Modafinil is an FDA-approved drug for the management of sleep disorders, such as narcolepsy, sleep apnea, and excessive daytime sleepiness.

6. psychiatryonline.org psychiatryonline.org/doi/pdf/10.1176/appi.ajp-rj.2022.170402

Modafinil: A Review and Its Potential Use in the Treatment ... This article describes findings from a literature review that focused on modafinil's mechanisms of action and its possible role in treating the fatigue and.

7. withpower.com withpower.com/trial/phase-2-post-acute-covid-19-pacs-or-long-covid-syndrome-6-2024-3df2c

Modafinil + Solriamfetol for Excessive Daytime Sleepiness ... Modafinil and Solriamfetol have been studied for safety in treating excessive daytime sleepiness in conditions like narcolepsy and obstructive sleep apnea.