Clinical trial NCT06874855: Lemborexant in Delayed Sleep Phase Syndrome
Official title: Lemborexant in Delayed Sleep Phase Syndrome
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE4
Conditions: Delayed Sleep Phase Syndrome
Keywords: Delayed Sleep Phase Syndrome
Syndrome
Lemborexant
Lead sponsor: University of California, San Francisco
Sponsor class: OTHER
Collaborators: name: Eisai Co., Ltd.
name: Stanford University
First posted: 2025-03-13
Enrollment: 15
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: To evaluate whether Lemborexant is more effective than placebo in shortening sleep onset latency in patients with delayed sleep phase syndrome (both type 1 and type 2)
Primary purpose: TREATMENT

Brief summary: The purpose of the study is to evaluate whether Lemborexant is more effective than placebo in shortening sleep onset latency in patients with delayed sleep phase syndrome (both type 1 and type 2). This will be tracked using sleep logs as well as actigraphy.

In this 2-year study, the investigators will examine if Lemborexant administered 5-10 mg nightly taken at desired bedtime (at least 2 hours prior to self-reported sleep onset habitual time) can improve the symptoms of Delayed Sleep Phase Syndrome.

Detailed description: Delayed sleep phase syndrome (DSPS) is a disorder in which a person's sleep is delayed by two hours or more beyond what is considered an acceptable or conventional bedtime. The delayed sleep then causes difficulty in being able to wake up at the desired time. In DSPS, bedtime is shifted later than the general population such that individuals have difficulty getting enough sleep to meet their sleep need before they have to get up for their daytime obligations (work, school, childcare, etc.). As a result, patients experience daytime impairment including daytime sleepiness and cognitive impairment. DSPS, if maintained in adulthood is associated with numerous deleterious health effects, although causality is not well established. The prevalence of this condition is approximately 7-16% among adolescents and young adults.

Eligibility criteria: Inclusion Criteria:

- Participants will be required to be 18 years of age or older and have delayed sleep phase syndrome (DSPS). Questionnaires will be used to identify potential confounders and to confirm a potential diagnosis of DSPS based on ICSD3 criteria: a) Sleep is delayed by two hours or more beyond what is considered an acceptable or conventional bedtime for the subject (their desired bedtime). b) Subjects not able to fall asleep if trying to sleep before the later bedtime; c) This is interfering with their wishes/having a social impact. Concomitant medications will be allowed, though dosages will be required to remain fixed throughout participation in the study. The participant also needs to be willing and able to comply with all aspects of the protocol.

Exclusion Criteria:

* Clinically significant depression (PHQ-9 score of 10 or more), anxiety disorder (GAD- 7 score of 10 or more), substance use disorder, any other sleep disorder, or any medical disorder/therapy that could interfere with the trial
* Use of medications with significant effects on sleep-wake function (insomnia therapies, stimulants)- unless they are discontinued at least 5 half-lives prior to study participation. Non-sedative antidepressants or SSRI will be allowed if at a stable dose in the absence of concomitant severe depression or severe anxiety.
* Use of CYP3A inhibitors and CYP3A inducers, at least 1 week (or five half-lives, whichever is longer) prior to the first day of the baseline phase.
* Pregnancy (verified by urine pregnancy test on visits 1, 2, and 3) or plan to become pregnant in the next 3 months or currently breastfeeding.
* Shift workers or subjects working unusual hours.
* Transmeridian travel across more than 3 time zones 4 weeks prior to the screening phase.
* Transmeridian travel across more than 2 time zones during this trial (including the screening phase).
* Having a positive drug test or being unwilling to refrain from using illegal drugs or marijuana during this trial.
* Any clinically abnormal symptom or organ impairment found by medical history at Screening or Baseline and physical examinations, vital signs, or laboratory test results that require medical treatment.
* Impaired liver function (values for enzymes aspartate transaminase (AST) and alanine transaminase (ALT) \> 1.5 times the Upper Limit of Normal).
* Known to be human immunodeficiency virus positive.

Primary outcomes:
measure: Change in actigraphy sleep latency onset
timeFrame: From 2 weeks prior to randomization to 4 weeks post randomization
Secondary outcomes:
measure: Change in Epworth Sleepiness Scale (ESS)
timeFrame: From randomization to 4 weeks post randomization
measure: Change in Karolinska Sleepiness Scale (KSS)
timeFrame: From randomization to 4 weeks post randomization
measure: Change in sleep diary derived sleep onset latency
timeFrame: From 2 weeks prior to randomization to 4 weeks post randomization
measure: Sleep Regularity Index
timeFrame: From 2 weeks prior to randomization to 4 weeks post randomization
measure: Change in actigraphy derived total sleep time
timeFrame: From 2 weeks prior to randomization to 4 weeks post randomization
measure: Change in sleep diary derived total sleep time.
timeFrame: From 2 weeks prior to randomization to 4 weeks post randomization
measure: Change in mean actigraphy derived wake time
timeFrame: From 2 weeks prior to randomization to 4 weeks post randomization
measure: Change in mean sleep diary derived wake time
timeFrame: From 2 weeks prior to randomization to 4 weeks post randomization
Other outcomes:
Locations:
city: San Francisco
country: United States
facility: University of California San Francisco
state: California
Study officials:
affiliation: University of California, San Francisco
name: Andrew D Krystal, MD, MS
role: PRINCIPAL_INVESTIGATOR
References:
citation: Duffy JF, Dijk DJ, Hall EF, Czeisler CA. Relationship of endogenous circadian melatonin and temperature rhythms to self-reported preference for morning or evening activity in young and older people. J Investig Med. 1999 Mar;47(3):141-50.
citation: Micic G, Richardson C, Cain N, Reynolds C, Bartel K, Maddock B, Gradisar M. Readiness to change and commitment as predictors of therapy compliance in adolescents with Delayed Sleep-Wake Phase Disorder. Sleep Med. 2019 Mar;55:48-55. doi: 10.1016/j.sleep.2018.12.002. Epub 2018 Dec 14.
citation: Zeitzer JM, Joyce DS, McBean A, Quevedo YL, Hernandez B, Holty JE. Effect of Suvorexant vs Placebo on Total Daytime Sleep Hours in Shift Workers: A Randomized Clinical Trial. JAMA Netw Open. 2020 Jun 1;3(6):e206614. doi: 10.1001/jamanetworkopen.2020.6614.
citation: Zeitzer JM, Buckmaster CL, Lyons DM, Mignot E. Increasing length of wakefulness and modulation of hypocretin-1 in the wake-consolidated squirrel monkey. Am J Physiol Regul Integr Comp Physiol. 2007 Oct;293(4):R1736-42. doi: 10.1152/ajpregu.00460.2007. Epub 2007 Aug 8.
citation: Zhang S, Zeitzer JM, Yoshida Y, Wisor JP, Nishino S, Edgar DM, Mignot E. Lesions of the suprachiasmatic nucleus eliminate the daily rhythm of hypocretin-1 release. Sleep. 2004 Jun 15;27(4):619-27. doi: 10.1093/sleep/27.4.619.