Ultradian Sleep/Wake Protocol for Sleep Patterns

(CARRS-P1 Trial)

Overseen By Ronette Blake, MS

Age: < 18

Sex: Any

Trial Phase: Academic

Sponsor: University of Pittsburgh

Must not be taking: Antidepressants, Sleep medications

Disqualifiers: Drug use, Seizures, Bipolar, others

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

Compensation: Varies

Number of Visits: 8

96 Participants Needed

Trial Summary

What is the purpose of this trial?

Adolescence is a time of heightened reward sensitivity and greater impulsivity. On top of this, many teenagers experience chronic sleep deprivation and misalignment of their circadian rhythms due to biological shifts in their sleep/wake patterns paired with early school start times, which may increase the risk for substance use (SU). However, what impact circadian rhythm and sleep disruption either together or independently have on the neuronal circuitry that controls reward and cognition, or if there are interventions that might help to modify these disruptions is unknown. Project 1 (P1), specifically examines homeostatic and circadian characteristics as mechanisms linking habitual sleep patterns, reward and cognitive control (at subjective, behavioral, and circuit levels), and longitudinal substance use risk.

Will I have to stop taking my current medications?

The trial may require you to stop taking certain medications, especially those that impact sleep/wake function. Some medications might be okay if you can stop them before and/or during the study procedures.

What data supports the effectiveness of the Ultradian sleep/wake protocol treatment for sleep patterns?

Research suggests that ultradian rhythms, which are shorter cycles within the 24-hour day, play a role in sleep patterns and adaptability. Studies have shown that ultradian rhythms can influence sleep stages and transitions, which may help in managing sleep-wake cycles. ^{1 2 3 4 5}

Is the Ultradian Sleep/Wake Protocol safe for humans?

The available research does not provide specific safety data for the Ultradian Sleep/Wake Protocol, but studies involving similar sleep patterns in controlled settings have not reported significant safety concerns. ^{1 6 7 8 9}

How does the Ultradian Sleep/Wake Protocol treatment differ from other treatments for sleep pattern issues?

The Ultradian Sleep/Wake Protocol is unique because it focuses on the natural ultradian rhythm, which is the cycle of NREM and REM sleep stages, rather than just the circadian rhythm (24-hour cycle). This approach may help regulate sleep patterns by aligning with the body's inherent sleep stage transitions, offering a novel way to address sleep issues. ^{1 2 8 10 11}

Research Team

Peter L. Franzen, PhD

Principal Investigator

University of Pittsburgh

Eligibility Criteria

This trial is for healthy teenagers aged 13-15 who attend a traditional high school and are not home-schooled. They must not have sleep apnea, be within a certain weight range, and cannot have serious medical conditions or a history of substance use. Those on certain medications or with MRI contraindications like metal implants can't participate.

Inclusion Criteria

I am between 13 and 15 years old.

I am in good physical and mental health.

Provision of written informed consent and assent

Exclusion Criteria

History of alcohol, cannabis, or illicit drug use in the past month, or greater than monthly use in the past year

I have a sleep disorder that is not insomnia or Delayed Sleep Phase Disorder.

I am not between the ages of 13 and 15.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2 weeks

Home monitoring with actigraphy and sleep diary

Baseline Assessment

Participants complete fMRI measures of reward and cognitive control

1-2 weeks

1 visit (in-person)

Laboratory Study

Participants undergo a 60-hour laboratory study including polysomnography and ultradian sleep/wake protocol

60 hours

1 visit (in-person)

Follow-up

Longitudinal online surveys to assess substance use

Up to 4.5 years

Online surveys every 6 months

Treatment Details

Interventions

• Ultradian sleep/wake protocol

Trial Overview The study investigates how disrupted sleep patterns and circadian rhythms affect reward systems and cognitive control in adolescents, potentially influencing substance use risk. It involves an ultradian sleep/wake protocol to assess these effects at subjective, behavioral, and neural circuit levels.

Participant Groups

Group I: Ultradian Sleep/Wake protocol Experimental Treatment 1 Intervention

This study uses an ultradian sleep/wake protocol to examine circadian and homeostatic sleep systems and their contributions to reward and cognitive control function. All participants will undergo the ultradian sleep/wake protocol following a night of sleep in the lab (measured with polysomnography) for 36 hours. The ultradian sleep/wake protocol will last for 36 h, during which every 120-minutes, there will be an 80-minute period of waking, followed by a 40-minute sleep opportunity. A repeat night of sleep will occur at the end of the 36-hour ultradian sleep/wake protocol.

Who Is Running the Clinical Trial?

University of Pittsburgh

Lead Sponsor

Trials

1,820

Recruited

16,360,000+

National Institute on Drug Abuse (NIDA)

Collaborator

Trials

2,658

Recruited

3,409,000+

Findings from Research

In a study involving 9 young adults, a 15-minute waking and 5-minute sleeping schedule over 12 hours revealed a rhythmic pattern in stage 1 sleep, suggesting a potential ultradian rhythm in sleepiness with a frequency of about 14.4 cycles per day.

Both REM deprivation and total sleep deprivation disrupted the normal periodicity of stage 1 sleep and altered stage 2 sleep distribution, indicating that sleep deprivation can significantly affect sleep architecture and the body's natural sleep-wake cycles.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ultrashort sleep-walking schedule. I. Evidence of ultradian rhythmicity in "sleepability'. Lavie, P., Scherson, A.[2019]

The study provides insights into the mechanisms behind the ultradian rhythm of REM sleep, showing that specific probabilities of sleep stage transitions can reproduce the typical 90-minute intervals of REM onset.

Increased transitions from light to deep NREM sleep were found to prolong the intervals between REM sleep, indicating that the dynamics of sleep stages play a crucial role in regulating REM sleep patterns.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Markov modeling of sleep stage transitions and ultradian REM sleep rhythm. Kishi, A., Yamaguchi, I., Togo, F., et al.[2019]

Circadian rhythm sleep-wake disorders (CRSWD) significantly impair health and functioning, and accurate diagnosis can be achieved through a 14-day assessment using sleep diaries, logs, and actigraphy.

The most effective treatments for CRSWD include melatonin administration and light therapy, along with recommended behavioral interventions, which can be tailored based on the patient's circadian phase.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment guidelines for Circadian Rhythm Sleep-Wake Disorders of the Polish Sleep Research Society and the Section of Biological Psychiatry of the Polish Psychiatric Association. Part I. Physiology, assessment and therapeutic methods. Wichniak, A., Jankowski, KS., Skalski, M., et al.[2022]

In narcolepsy, while the homeostatic process of sleep is maintained, the circadian regulation of sleep/wake cycles is disrupted, leading to significant alterations in sleep patterns.

Patients with narcolepsy exhibit a strong ultradian rhythm, characterized by a 4-hour cycle of Slow Wave Activity and a longer 2-hour NREM/REM cycle, which contributes to the symptoms of the disorder.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Circadian and ultradian cycles in narcolepsy]. Espa, F., Besset, A.[2006]

Circadian rhythm sleep disorders arise from a mismatch between the body's natural rhythms and conventional sleep-wake schedules, which can disrupt optimal sleep and alertness.

Evaluating these disorders requires careful monitoring of sleep patterns over several days to weeks, highlighting the importance of understanding individual sleep-wake cycles for effective treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Circadian rhythm sleep disorders. Kanathur, N., Harrington, J., Lee-Chiong, T.[2010]

Circadian rhythm sleep-wake disorders (CRSWD) are frequently misdiagnosed as insomnia or hypersomnia, highlighting the importance of thorough patient interviews and the use of sleep diaries and actigraphy for accurate diagnosis.

The recommended treatment for CRSWD includes chronotherapy methods such as melatonin, light therapy, and behavioral interventions, rather than relying on hypnotics or psychostimulants, which may only mask symptoms without addressing the underlying disorder.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment guidelines for Circadian Rhythm Sleep - Wake Disorders of the Polish Sleep Research Society and the Section of Biological Psychiatry of the Polish Psychiatric Association. Part II. Diagnosis and treatment. Wichniak, A., Jankowski, KS., Skalski, M., et al.[2018]

Recent guidelines and studies highlight effective treatments for various circadian rhythm sleep-wake disorders, including delayed sleep-wake phase disorder and shift work, emphasizing the importance of personalized approaches.

Innovative methods for estimating circadian phase, such as home saliva collection for melatonin onset and new light treatment technologies, show promise in improving treatment outcomes for these disorders.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Circadian-Based Therapies for Circadian Rhythm Sleep-Wake Disorders. Burgess, HJ., Emens, JS.[2020]

The study confirmed that the REM-NREM sleep rhythm has a stable period over long-term observations, even under various conditions such as undisturbed sleep and altered sleep-wake cycles, involving 6 test subjects and 1 patient.

The ultradian REM sleep rhythm operates independently of the 24-hour day cycle, suggesting it is controlled internally and can drift daily, indicating a distinct mechanism from circadian rhythms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Studies on the stability of human ultradian rhythms (author's transl)]. Schulz, H., Dirlich, G., Zulley, J.[2006]

Circadian rhythm sleep-wake disorders (CRSWD) affect a significant number of people in the U.S., with estimates ranging from 800,000 to 3 million individuals, highlighting a critical need for improved diagnosis and treatment.

The workshop identified key areas for high-priority research in CRSWD, emphasizing the importance of understanding the mechanisms behind these disorders to enhance patient care and outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Workshop report. Circadian rhythm sleep-wake disorders: gaps and opportunities. Duffy, JF., Abbott, SM., Burgess, HJ., et al.[2022]

In a study involving 10 healthy young men, the administration of risperidone altered the ultradian rhythm of REM sleep by prolonging the intervals between REM periods, which affected the transition probabilities between different NREM sleep stages.

The findings suggest that the transitions from light NREM sleep (N2) to deep NREM sleep (N3) are crucial in regulating the timing of REM sleep, indicating a potential mechanism behind the ultradian REM sleep rhythm.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

NREM sleep stage transitions control ultradian REM sleep rhythm. Kishi, A., Yasuda, H., Matsumoto, T., et al.[2021]

The regulation of sleep involves three processes: homeostatic, circadian, and ultradian, with the homeostatic process reflecting recovery during wakefulness and sleep.

Narcoleptic patients show a heightened sensitivity to homeostatic sleep regulation but have a weaker circadian process, leading to more frequent daytime sleep episodes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Regulation of sleep]. Besset, A.[2006]

References

1. Ireland pubmed.ncbi.nlm.nih.gov

Ultrashort sleep-walking schedule. I. Evidence of ultradian rhythmicity in "sleepability'. [2019]

2. England pubmed.ncbi.nlm.nih.gov

Markov modeling of sleep stage transitions and ultradian REM sleep rhythm. [2019]

3. Poland pubmed.ncbi.nlm.nih.gov

Treatment guidelines for Circadian Rhythm Sleep-Wake Disorders of the Polish Sleep Research Society and the Section of Biological Psychiatry of the Polish Psychiatric Association. Part I. Physiology, assessment and therapeutic methods. [2022]

4. France pubmed.ncbi.nlm.nih.gov

[Circadian and ultradian cycles in narcolepsy]. [2006]

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

Circadian rhythm sleep disorders. [2010]

6. Poland pubmed.ncbi.nlm.nih.gov

Treatment guidelines for Circadian Rhythm Sleep - Wake Disorders of the Polish Sleep Research Society and the Section of Biological Psychiatry of the Polish Psychiatric Association. Part II. Diagnosis and treatment. [2018]

7. Switzerland pubmed.ncbi.nlm.nih.gov

Circadian-Based Therapies for Circadian Rhythm Sleep-Wake Disorders. [2020]

8. Germany pubmed.ncbi.nlm.nih.gov

[Studies on the stability of human ultradian rhythms (author's transl)]. [2006]

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

Workshop report. Circadian rhythm sleep-wake disorders: gaps and opportunities. [2022]

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

NREM sleep stage transitions control ultradian REM sleep rhythm. [2021]

11. France pubmed.ncbi.nlm.nih.gov

[Regulation of sleep]. [2006]