Ultradian Sleep/Wake Protocol for Sleep Patterns
(CARRS-P1 Trial)
Recruiting in Palo Alto (17 mi)
PL
Overseen byPeter L. Franzen, PhD
Age: < 18
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Academic
Recruiting
Sponsor: University of Pittsburgh
Must not be taking: Antidepressants, Sleep medications
Disqualifiers: Drug use, Seizures, Bipolar, others
No Placebo Group
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?
Is the Ultradian Sleep/Wake Protocol safe for humans?
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.1281011
Research Team
PL
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
See 1 more
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.
See 10 more
Trial 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 (Behavioral Intervention)
Trial OverviewThe 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
1Treatment groups
Experimental Treatment
Group I: Ultradian Sleep/Wake protocolExperimental Treatment1 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.
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Western Psychiatric HospitalPittsburgh, PA
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Who Is Running the Clinical Trial?
University of Pittsburgh
Lead Sponsor
Trials
1820
Patients Recruited
16,360,000+
National Institute on Drug Abuse (NIDA)
Collaborator
Trials
2658
Patients Recruited
3,409,000+
References
Ultrashort sleep-walking schedule. I. Evidence of ultradian rhythmicity in "sleepability'. [2019]After a 7-8 h sleep at home, 9 young adults were placed on an ultrashort 15 min waking-5 min sleeping schedule for 12 consecutive hours, followed by a monitored recovery night in the laboratory. Six of 4 of the 9 subjects were also investigated in the same way after one night of selective REM deprivation and after one night of total sleep deprivation, respectively. In the first experiment, the amount of stage 1 in each of the sleep attempts varied rhythmically with a frequency of about 14.4 c/day. The average variance at the peak spectral frequency significantly exceeded the mean variance at the rest of the spectral frequencies and the mean variance at the adjacent frequencies. Stage 2 occurred more often around 15-16 h, with no evidence of ultradian rhythmicity. Both REM deprivation and total sleep deprivation disrupted the 100 min periodicity in stage 1 and modified the distribution of stage 2 toward a bimodal rather than a unimodal distribution. The result of the first experiment were interpreted in the light of Kleitman's BRAC model. The ultradian rhythmicity in sleepiness is suggested to play a role in the adaptability and flexibility of the circadian sleep-waking cycle.
Markov modeling of sleep stage transitions and ultradian REM sleep rhythm. [2019]One of the highly characteristic features of sleep is the cyclic occurrence of non-rapid eye movement (NREM) and REM sleep, which is referred to as the ultradian rhythm of sleep. Even though REM sleep was discovered over half a century ago, surprisingly, the mechanism of the ultradian REM sleep rhythm has not yet been fully elucidated. In the present study, we aim to provide a mechanistic insight into the generation of the ultradian REM sleep rhythm. Approach and Main results: By simulating hypnograms with the dynamic features of sleep stage transitions, i.e. stage transition probabilities and stage-specific survival time functions, we show that the second-order Markov transition probabilities and the stage-specific survival time functions can reproduce the central position (∼90 min) of the REM-onset intervals (ROIs), but with a larger variance in distribution. In addition, we demonstrate the direct effect of the increased probability of the transitions from light to deep sleep within NREM sleep on the prolongation of the ROIs in a dose-response manner.
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]Majority of the physiological processes in the human organism are rhythmic. The most common are the diurnal changes that repeat roughly every 24 hours, called circadian rhythms. Circadian rhythms disorders have negative influence on human functioning. The aim of this article is to present the current understanding of the circadian rhythms physiological role, with particular emphasis on the circadian rhythm sleep-wake disorders (CRSWD), principles of their diagnosis and chronobiological therapy. The guidelines are based on the review of recommendations from the scientific societies involved in sleep medicine and the clinical experiences of the authors. Researchers participating in the preparation of guidelines were invited by the Polish Sleep Research Society and the Section of Biological Psychiatry of the Polish Psychiatric Association, based on their significant contributions in circadian rhythm research and/or clinical experience in the treatment of such disorders. Finally, the guidelines were adjusted to the questions and comments given by the members of both Societies. CRSWD have a significant negative impact on human health and functioning. Standard methods used to assess CRSWD are sleep diaries and sleep logs, while the actigraphy, when available, should be also used. The most effective methods of CRSWD treatment are melatonin administration and light therapy. Behavioral interventions are also recommended. Afourteen-day period of sleep-wake rhythm assessment in CRSWD enables accurate diagnosis, adequate selection of chronobiological interventions, and planning adequate diurnal timing of their application. This type of assessment is quite easy, low-cost, and provides valuable indications how to adjust the therapeutic approach to the circadian phase of the particular patient.
[Circadian and ultradian cycles in narcolepsy]. [2006]In narcolepsy, homeostatic process is preserved while sleep/wake circadian process is impaired. Other circadian components (body temperature, endocrine secretions, subjective sleepiness) are preserved. This circadian system weakness permits the occurrence of a very strong ultradian component, modulating sleep/wake rhythm. So, a 4 hour ultradian rhythmicity of Slow Wave Activity, and a 2 hour NREM/REM cycle longer than in normal subjects, has been evidenced in narcoleptic patients. These circadian and ultradian alterations can explain a major part of the narcoleptic symptoms.
Circadian rhythm sleep disorders. [2010]Because there is insufficient cellular energy for organisms to perform their functions at the same constant rate and at the same time, all biologic processes show rhythmicity, each with its own unique frequency, amplitude, and phase. Optimal sleep and wakefulness requires proper timing and alignment of desired sleep-wake schedules and circadian rhythm-related periods of alertness. Persistent or recurrent mismatch between endogenous circadian rhythms and the conventional sleep-wake schedules of the environmental day can give rise to several circadian rhythm sleep disorders. Evaluation of suspected circadian rhythm sleep disorders requires proper monitoring of sleep diaries, often over several days to weeks. This article discusses the disorders of the circadian sleep-wake cycle and the therapeutic measures to correct the same.
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]Circadian rhythm sleep-wake disorders (CRSWD) are a group of disorders, in which the timing of sleep and wakefulness significantly differs from a patient's expectations or socially acceptable times. The aimof the article is to present the current principles for the diagnosis and treatment of CRSWD in adults and children.
Circadian-Based Therapies for Circadian Rhythm Sleep-Wake Disorders. [2020]This review summarizes recent developments relevant to the treatment of circadian rhythm sleep-wake disorders. The clinical practice guidelines for the treatment of intrinsic circadian rhythm sleep-wake disorders is described, followed by recent treatment studies for delayed sleep-wake phase disorder, non-24 hour sleep-wake disorder, irregular sleep-wake disorder and shift work. New methods to estimate circadian phase, including home saliva collection to estimate the dim light melatonin onset, circadian questionnaires and general rules to guide light and exogenous melatonin treatments are described. New developments in light treatment are detailed, including light flashes during sleep and wearable light devices. Substances such as caffeine and alcohol, and devices such as electronic tablets are also considered for their potential to shift circadian timing. Finally, an update on melatonin supplements in the US is discussed, along with the controversy surrounding the use of melatonin supplements in patients with prediabetes or diabetes.
[Studies on the stability of human ultradian rhythms (author's transl)]. [2006]It was investigated whether the REM-NREM (rapid eye movement-non-REM) sleep rhythm has a stable period during long-term observations. Sequences of 17 to 31 consecutive sleep records were analyzed for 6 test subjects and 1 patient. Period stability was confirmed for three experimental conditions: a) undisturbed night sleep, b) inversion of the sleep-waking cycle, c) absence of external timing mechanisms. The period of the ultradian REM sleep rhythm is no integral submultiple of 24 h, so that the remainder causes a daily drift in the REM sleep rhythm. It is assumed that the ultradian process is controlled endogenously. In contrast to the circadian rhythm the ultradian rhythm appears to be free-running under normal conditions. The stability of the ultradian period has been shown in long-term observations.
Workshop report. Circadian rhythm sleep-wake disorders: gaps and opportunities. [2022]This White Paper presents the results from a workshop cosponsored by the Sleep Research Society (SRS) and the Society for Research on Biological Rhythms (SRBR) whose goals were to bring together sleep clinicians and sleep and circadian rhythm researchers to identify existing gaps in diagnosis and treatment and areas of high-priority research in circadian rhythm sleep-wake disorders (CRSWD). CRSWD are a distinct class of sleep disorders caused by alterations of the circadian time-keeping system, its entrainment mechanisms, or a misalignment of the endogenous circadian rhythm and the external environment. In these disorders, the timing of the primary sleep episode is either earlier or later than desired, irregular from day-to-day, and/or sleep occurs at the wrong circadian time. While there are incomplete and insufficient prevalence data, CRSWD likely affect at least 800,000 and perhaps as many as 3 million individuals in the United States, and if Shift Work Disorder and Jet Lag are included, then many millions more are impacted. The SRS Advocacy Taskforce has identified CRSWD as a class of sleep disorders for which additional high-quality research could have a significant impact to improve patient care. Participants were selected for their expertise and were assigned to one of three working groups: Phase Disorders, Entrainment Disorders, and Other. Each working group presented a summary of the current state of the science for their specific CRSWD area, followed by discussion from all participants. The outcome of those presentations and discussions are presented here.
NREM sleep stage transitions control ultradian REM sleep rhythm. [2021]The cyclic sequence of NREM and REM sleep, the so-called ultradian rhythm, is a highly characteristic feature of sleep. However, the mechanisms responsible for the ultradian REM sleep rhythm, particularly in humans, have not to date been fully elucidated. We hypothesize that a stage transition mechanism is involved in the determination of the ultradian REM sleep rhythm.
[Regulation of sleep]. [2006]Sleep regulation calls for 3 processes: the first one is the homeostatic process increasing during wakefulness and decreasing during sleep, the second one is the circadian process depending on the circadian oscillator which controls temperature and alertness rhythms, and the third one is the ultradian process: it determines the NREM/REM periodicity. In the 2 process model of sleep regulation, the power density of the delta band (0.75-4.5 Hz) called slow wave activity (SWA) and obtained by spectral analysis, is supposed to reflect the variations of a homeostatic recovery process (process S) that increases in a saturating exponential way during wakefulness. Its decrease is expressed by the exponential decline of SWA during sleep. Process S interacts with the circadian process (process S) that determines the sleep timing. The 2 process model has been further modified to account for the semicircadian sleep propensity, although no satisfactory fit has been obtained with laboratory data. No impairment of NREM sleep homeostatic sleep regulation can be evidenced in narcoleptic patients who seem more sensitive to homeostatic regulation of sleep than normal subjects. On the other hand the circadian process appears to be weaker in narcoleptic patients than in normal subjects; this permits the occurrence of a strong ultradian component explaining diurnal sleep episodes.