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

Trial Summary

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 the combination of Modafinil and Solriamfetol safe for treating excessive daytime sleepiness?

Modafinil and Solriamfetol have been studied for safety in treating excessive daytime sleepiness in conditions like narcolepsy and obstructive sleep apnea. Modafinil has been used since 1998, but its use is now limited to narcolepsy due to safety reviews. Solriamfetol is generally well tolerated, with common side effects including headache, nausea, decreased appetite, insomnia, and anxiety. ^{1 2 3 4 5}

How is the drug combination of Modafinil and Solriamfetol unique for treating excessive daytime sleepiness from Long COVID?

This drug combination is unique because it combines Modafinil, a central nervous system stimulant, with Solriamfetol, a dopamine-norepinephrine reuptake inhibitor, both of which are used to improve wakefulness in conditions like narcolepsy and obstructive sleep apnea. This combination may offer a novel approach to managing excessive daytime sleepiness in Long COVID, a condition with no standard treatment. ^{1 4 6 7 8}

What is the purpose of this trial?

The platform protocol is designed to be flexible so that it is suitable for a range of study settings and intervention types. Therefore, the platform protocol provides a general protocol structure that can be shared by multiple interventions and allows comparative analysis across the interventions. For example, objectives, measures, and endpoints are generalized in the platform protocol, but intervention-specific features are detailed in separate appendices. This platform protocol is a prospective, multi-center, multi-arm, randomized controlled platform trial evaluating potential interventions for PASC-mediated sleep disturbances. The hypothesis is that symptoms of sleep and circadian disorders that emerge in patients with PASC can be improved by phenotype-targeted interventions. Specific sleep and circadian disorders addressed in this protocol include sleep-related daytime impairment (referred to as hypersomnia) and complex PASC-related sleep disturbance (reflecting symptoms of insomnia and sleep-wake rhythm disturbance).

Research Team

Christina Barkauskas, MD

Principal Investigator

Duke Clinical Research Institute

Susan Redline, MD MPH

Principal Investigator

Brigham and Women's Hospital

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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 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]

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 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]

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]

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]

References

1. United States 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. [2021]

2. New Zealand 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. [2021]

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

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

4. Netherlands 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. [2021]

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

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

6. 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]

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

Modafinil for the Improvement of Patient Outcomes Following Traumatic Brain Injury. [2020]

8. Netherlands 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. [2023]