Clinical trial NCT05336084: Circadian Rhythms and Homeostatic Sleep Drive and Their Effect on Reward and Cognitive Control Systems in Adolescents
Official title: Center for Adolescent Reward, Rhythms and Sleep Project 1
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Sleep
Keywords: adolescence
sleep
substance use
reward sensitivity and motivation
circadian phase and alignment
homeostatic sleep drive
ultradian sleep/wake schedule
Lead sponsor: University of Pittsburgh
Sponsor class: OTHER
Collaborators: name: National Institute on Drug Abuse (NIDA)
First posted: 2022-04-20
Enrollment: 96
Sex: ALL
Minimum age (years): 13
Maximum age (years): 15
Standard ages: CHILD
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: BASIC_SCIENCE

Brief summary: 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.

Detailed description: P1 will study 96 adolescents ages 13-15, stratified by habitual sleep timing (early, intermediate, late), in a 60-h laboratory study. Participants will monitor sleep patterns at home for 2 weeks with actigraphy and sleep diary, and will also complete fMRI measures of reward and cognitive control. This will be followed by a 60-hour laboratory visit. The laboratory session includes two nights of polysomnography (PSG) sleep studies, separated by 36 h of an ultradian sleep/wake protocol-every 120-minutes, there will be an 80-minute period of waking, followed by a 40-minute sleep opportunity. Participants will be in dim light conditions and temporal isolation for the first 24 h of the ultradian sleep/wake protocol. Physiological circadian measures include salivary melatonin; core body temperature (CBT); and molecular rhythms from hair follicle cells (examined in Project 3). Physiological sleep homeostatic measures include waking EEG theta power, slow-wave sleep rebound following the 36-h ultradian sleep/wake protocol, and repeated sleep latency on the sleep opportunities. Behavioral tests (Reward Anti-Saccade task to index cognitive control with/without reward modulation; Psychomotor Vigilance Test) and self-reports of mood/sleepiness will be collected every 2 h. Longitudinal on-line surveys will assess substance use every 6 months for the life of the grant.

Eligibility criteria: Inclusion Criteria:

* Age 13-15 years
* Currently enrolled in a traditional high-school (not cyber- or home-schooled) \[school closures during the COVID-19 pandemic are an exception to this\]
* Physically and psychiatrically healthy
* Provision of written informed consent and assent

Exclusion Criteria:

* outside age range above
* have a history of alcohol, cannabis, or illicit drug use in the past month, or greater than monthly use in the past year
* have serious medical or neurological disorders, including history of seizures
* have serious psychiatric disorders (e.g. bipolar disorder and schizophrenia)
* taking antidepressants (SSRIs/SSNIs are OK) or medications known to impact sleep/wake function - some medications may be okay if willing and able to discontinue prior to and/or for laboratory procedures
* have sleep disorders other than insomnia or Delayed Sleep Phase Disorder
* have MRI contraindications (i.e., metal in the body; claustrophobia)
* first degree relative with bipolar disorder
* frequent headaches or migraines
* inability to swallow pills/capsules.
* pregnancy
* participants with observed Obstructive Sleep Apnea via Apnealink, as indicated by an Apnea Hypopnea Index (AHI) of greater than 5
* Less than 80 lbs. or a BMI of greater than 35

Primary outcomes:
measure: Change in EEG delta power across overnight polysomnography on the night preceding vs. following the 36-hour ultradian sleep/wake protocol.
timeFrame: The first night of sleep preceding the 36-hour ultradian sleep/wake protocol vs the night of sleep following the ultradian sleep/wake protocol
measure: Change in slope of waking EEG theta power
timeFrame: Every 2 hours during the 36-hour ultradian sleep/wake protocol
measure: Melatonin onset
timeFrame: The first 24-hours of the ultradian sleep/wake protocol
Secondary outcomes:
measure: Circadian pattern of Core Body Temperature (CBT)
timeFrame: Measured continuously across the 36-hour ultradian sleep/wake protocol.
measure: Melatonin amplitude
timeFrame: Collected every 30-60 minutes across the first 24-hours of the ultradian sleep/wake protocol
measure: Sleep latency
timeFrame: During the 40-minute sleep opportunities collected every two hours across the 36-hour ultradian sleep/wake protocol.
measure: Influence of sleep and circadian measures on neural correlates of impulse control
timeFrame: Measures from the 36-hour ultradian sleep/wake protocol in relation to an fMRI scan measured 1 to 2 weeks earlier.
measure: Influence of sleep and circadian measures on neural correlates of reward anticipation and reward outcome.
timeFrame: 1 to 2 weeks before to immediately after the 36-hour ultradian sleep/wake protocol.
measure: Performance on the Psychomotor Vigilance Task
timeFrame: 1 to 2 weeks before to immediately after the 36-hour ultradian sleep/wake protocol.
measure: Performance on the Reward Anti-Saccade task
timeFrame: Measures collected every two hours during the 36-hour ultradian sleep/wake protocol.
measure: Substance use
timeFrame: Every 6 months for the duration of the study, up to 4.5 years
Other outcomes:
Locations:
city: Pittsburgh
country: United States
facility: Western Psychiatric Hospital
state: Pennsylvania
Study officials:
affiliation: University of Pittsburgh
name: Peter L. Franzen, PhD
role: PRINCIPAL_INVESTIGATOR
References: