Tasimelteon for REM Sleep Behavior Disorder

(RBD Trial)

Overseen By Milena Pavlova, M.D.

Age: 18+

Sex: Any

Trial Phase: Phase < 1

Sponsor: Brigham and Women's Hospital

Disqualifiers: Contraindication to tasimelteon, others

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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 4 weeks

20 Participants Needed

Trial Summary

What is the purpose of this trial?

To assess the effects of a daily single oral dose of 20 mg tasimelteon compared to baseline on events of dream enactment on patients with REM Behavior Disorder, as measured by a daily log. To assess the effects of 20 mg tasimelteon compared to baseline on insomnia= symptoms, as measured by validated questionnaires (Insomnia Severity Index \[ISI\], Pittsburgh Sleep Quality Inventory \[PSQI\], Epworth Sleepiness Scale \[ESS\], Clinical Global Impression of Change Scale (CGI-C), Patient Global Impression of Change Scale (PGI-C)) as well as rest/activity pattern from actigraphy. * To assess the effects of 20 mg tasimelteon on patients who have a reduced or aberrant melatonin secretion compared to normal secretion by measuring salivary DLMO at baseline and correlating with the degree of change in RBD symptoms by end of the study. * To assess for any role a patient's unique genome may play in their response to tasimelteon; obtained via whole genome sequencing. * To assess the safety and tolerability of a daily single oral dose of 20 mg tasimelteon.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What data supports the effectiveness of the drug Tasimelteon for REM Sleep Behavior Disorder?

Tasimelteon is effective in treating non-24-hour sleep-wake disorder, especially in totally blind individuals, by helping them align their sleep patterns with the 24-hour day. It works by acting on melatonin receptors to adjust the body's internal clock, which might suggest potential benefits for other sleep-related disorders. ^{1 2 3 4 5}

How is the drug Tasimelteon unique for treating REM Sleep Behavior Disorder?

Tasimelteon is unique because it is a dual melatonin receptor agonist, specifically targeting the MT2 receptor, which is believed to help regulate circadian rhythms. It is the first drug approved for Non-24-Hour Sleep-Wake Disorder, showing its potential in managing sleep-related conditions by helping align the body's internal clock with the 24-hour day. ^{1 2 3 5 6}

Research Team

Milena Pavlova, MD

Principal Investigator

Brigham and Women's Hospital

Eligibility Criteria

This trial is for individuals who have been diagnosed with REM Sleep Behavior Disorder, confirmed by a sleep study. Participants must be able to engage in the trial activities and not have any medical or psychiatric conditions that could limit their participation or increase their risk.

Inclusion Criteria

I have been diagnosed with REM sleep behavior disorder through a sleep study.

I am able to take part in the clinical trial.

Exclusion Criteria

I cannot take tasimelteon due to health reasons.

I do not have any health or mental conditions that would make it unsafe for me to join.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Baseline

Participants maintain a daily sleep diary to establish baseline sleep patterns and dream enactment events

4 weeks

Daily self-reporting

Treatment

Participants receive a nightly dose of 20 mg tasimelteon and continue daily sleep diary entries

4 weeks

Daily self-reporting

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Tasimelteon

Trial Overview The trial is testing the effects of a daily dose of tasimelteon (20 mg) on dream enactment behaviors in RBD patients. It also examines its impact on insomnia symptoms using questionnaires and activity patterns via actigraphy, as well as how melatonin secretion levels and genetics might influence treatment response.

Participant Groups

Group I: Treatment Phase Experimental Treatment 1 Intervention

Tasimelteon will be administered in 20 mg capsules on a nightly basis for 4 weeks during the treatment phase.

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

Approved in United States as Hetlioz for:

• Non-24-Hour Sleep-Wake Disorder
• Nighttime sleep disturbances in Smith-Magenis Syndrome

Approved in European Union as Hetlioz for:

• Non-24-hour sleep-wake rhythm disorder in totally blind adults

Who Is Running the Clinical Trial?

Brigham and Women's Hospital

Lead Sponsor

Trials

1,694

Recruited

14,790,000+

Vanda Pharmaceuticals

Industry Sponsor

Trials

68

Recruited

19,900+

Findings from Research

Tasimelteon (Hetlioz®) is the first FDA-approved treatment for non-24-hour sleep-wake disorder, particularly effective in blind individuals, as it helps reduce nighttime wakefulness and daytime sleepiness by promoting synchronization to the 24-hour cycle.

The drug is well tolerated with common side effects including headaches and unusual dreams, and ongoing safety studies are being conducted to further assess its effects in blind patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tasimelteon for the treatment of non-24-hour sleep-wake disorder. Neubauer, DN.[2017]

In two phase III trials involving totally blind individuals with Non-24-Hour Sleep-Wake Disorder, tasimelteon (20 mg once nightly) significantly improved the ability to entrain the circadian pacemaker compared to placebo.

Tasimelteon was generally well tolerated and also led to improvements in sleep/wake parameters and overall functioning, making it a valuable treatment option for Non-24 in this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tasimelteon: A Review in Non-24-Hour Sleep-Wake Disorder in Totally Blind Individuals. Keating, GM.[2018]

Tasimelteon, the first approved treatment for Non-24-Hour Sleep-Wake Disorder, is a potent Dual Melatonin Receptor Agonist with significantly higher affinity for the MT2 receptor, which is important for regulating circadian rhythms.

In extensive testing, tasimelteon showed minimal interaction with over 160 other receptors and enzymes, suggesting a favorable safety profile and specificity for its intended action.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tasimelteon: a selective and unique receptor binding profile. Lavedan, C., Forsberg, M., Gentile, AJ.[2015]

Tasimelteon has been shown to significantly improve sleep initiation and maintenance in patients with Non-24-hour sleep-wake disorder, based on results from multiple clinical trials involving up to 412 participants.

The drug effectively shifts circadian rhythms, with significant improvements in sleep efficiency and entrainment observed, particularly at a dosage of 20 mg, although its high cost may limit accessibility for some patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tasimelteon: a melatonin receptor agonist for non-24-hour sleep-wake disorder. Johnsa, JD., Neville, MW.[2018]

Tasimelteon (Hetlioz™) is a melatonin-receptor agonist approved by the FDA in January 2014 specifically for treating non-24-hour sleep-wake disorder, indicating its targeted therapeutic use.

The article reviews tasimelteon's mechanism of action, pharmacokinetics, and its clinical efficacy, safety, and tolerability, highlighting its potential benefits for individuals with this specific sleep disorder.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tasimelteon (Hetlioz™): A New Melatonin Receptor Agonist for the Treatment of Non-24-Hour Sleep-Wake Disorder. Bonacci, JM., Venci, JV., Gandhi, MA.[2015]

Tasimelteon, a melatonin receptor agonist, is the first approved treatment for Non-24-hour Sleep-Wake Disorder, showing a strong affinity for the MT2 receptor, which helps regulate sleep cycles.

In a study involving 184 blind individuals over more than a year, tasimelteon was found to be safe and well-tolerated, with adverse effects similar to those seen in placebo groups, indicating its potential for long-term use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety profile of tasimelteon, a melatonin MT1 and MT2 receptor agonist: pooled safety analyses from six clinical studies. Leger, D., Quera-Salva, MA., Vecchierini, MF., et al.[2015]

References

1. Spain pubmed.ncbi.nlm.nih.gov

Tasimelteon for the treatment of non-24-hour sleep-wake disorder. [2017]

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

Tasimelteon: A Review in Non-24-Hour Sleep-Wake Disorder in Totally Blind Individuals. [2018]

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

Tasimelteon: a selective and unique receptor binding profile. [2015]

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

Tasimelteon: a melatonin receptor agonist for non-24-hour sleep-wake disorder. [2018]

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

Tasimelteon (Hetlioz™): A New Melatonin Receptor Agonist for the Treatment of Non-24-Hour Sleep-Wake Disorder. [2015]

6. England pubmed.ncbi.nlm.nih.gov

Safety profile of tasimelteon, a melatonin MT1 and MT2 receptor agonist: pooled safety analyses from six clinical studies. [2015]