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Sleep reactivity as a novel mechanism in Shift Work Disorder

Award Number: R01HL160870
ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 09/15/2022
PERIOD OF PERFORMANCE END DATE: 05/31/2026
AWARD TERMINATION DATE: 03/12/2026

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Sleep reactivity as a novel mechanism in Shift Work Disorder - Project Summary/Abstract All essential 24-hr operations (e.g., first responders, hospital services) rely on nightshift workers who forgo nocturnal sleep for work. Shift workers comprise 20% of the workforce, with 15 million regularly working nights. Most do not adapt to the inverted sleep-wake schedule, resulting in shift work disorder (SWD) characterized by excessive sleepiness and/or insomnia with sleep loss. Furthermore, because nightshifts are critical to safety- sensitive operations, the risk for catastrophic accidents makes SWD a threat to public health and safety. There remain critical gaps in the clinical translation of shift work research into validated treatments for SWD. One gap is a lack of mechanistic research in large clinical samples of SWD that probe pertinent treatment targets. As such, treatments have predominantly focused on symptom management (e.g., stimulants to maintain alertness and hypnotic medications for sleep). Symptom management alone leaves the underlying mechanisms unabated which can continue to cause a myriad of acute and long-term problems and morbidities. To address this gap, the overall objective of this proposal is to elucidate critical and novel mechanisms driving SWD. Our long-term goal is to develop a treatment that identifies and targets the appropriate underlying mechanisms in SWD. Our pilot data indicates that in addition to circadian misalignment (i.e., a mismatch between the body- clock and the sleep-work schedule), one novel and critical mechanism in SWD is sleep reactivity. Sleep reactivity is a trait where sleep is easily disrupted by environmental stimuli and stressors. Our pilot data in a cross-sectional sample suggests that sleep reactivity predicts persistent SWD symptoms even after reducing circadian misalignment. We also show that sleep reactivity can be reduced with Cognitive Behavioral Therapy (CBT). However, sleep reactivity has not been experimentally disassociated from circadian misalignment as an independent causal mechanism of SWD. This research is critical because it would demonstrate that SWD treatment should target sleep reactivity independently from circadian misalignment. To do this, we propose a two-step mechanistic randomized controlled trial in SWD stratified by high and low sleep reactivity (N=150): the first step probes circadian misalignment using timed bright light exposure, and the second step reduces sleep reactivity with Cognitive Behavioral Therapy. Our central hypothesis is that symptoms of SWD will reduce proportionately with circadian realignment in SWD with low sleep reactivity; however, both insomnia (Aim 1) and sleepiness (Aim 2) symptoms will persist in SWD with high sleep reactivity even after experimental reduction of circadian misalignment. In those with persistent symptoms despite reduced circadian misalignment, further reducing sleep reactivity with CBT would result in reductions in symptoms (Aims 3 & 4). Upon completion, results from this study will have established sleep reactivity as a novel causal mechanism of SWD to be inform future precision medicine approaches for this highly prevalent and undertreated disorder.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2026 ( Subtotal = $0 )
2026	2025	HENRY FORD HEALTH SYSTEM	1 FORD PL # 5B	DETROIT	MI	48202	WAYNE	USA	National Center on Sleep Disorders Research	000	4	3/12/2026	TERMINATION	$0
														Subtotal = $0

Issue Date FY: 2025 ( Subtotal = $683,293 )
2025	2025	HENRY FORD HEALTH SYSTEM	1 FORD PL	DETROIT	MI	48202	WAYNE	USA	National Center on Sleep Disorders Research	000	4	8/29/2025	NON-COMPETING CONTINUATION	$683,293
														Subtotal = $683,293

Issue Date FY: 2024 ( Subtotal = $672,607 )
2024	2024	HENRY FORD HEALTH SYSTEM	1 FORD PL	DETROIT	MI	48202	WAYNE	USA	National Center on Sleep Disorders Research	001	3	8/27/2024	NON-COMPETING CONTINUATION	$672,607
2024	2023	HENRY FORD HEALTH SYSTEM	1 FORD PL	DETROIT	MI	48202	WAYNE	USA	National Center on Sleep Disorders Research	000	2	6/21/2024	NON-COMPETING CONTINUATION	$0
														Subtotal = $672,607

Issue Date FY: 2023 ( Subtotal = $721,118 )
2023	2023	HENRY FORD HEALTH SYSTEM	1 FORD PL	DETROIT	MI	48202	WAYNE	USA	National Center on Sleep Disorders Research	001	2	8/19/2023	NON-COMPETING CONTINUATION	$721,118
2023	2022	HENRY FORD HEALTH SYSTEM	1 FORD PL	DETROIT	MI	48202	WAYNE	USA	National Center on Sleep Disorders Research	000	1	8/12/2023	NEW	$0
														Subtotal = $721,118

Issue Date FY: 2022 ( Subtotal = $759,979 )
2022	2022	HENRY FORD HEALTH SYSTEM	1 FORD PL	DETROIT	MI	48202	WAYNE	USA	National Center on Sleep Disorders Research	001	1	9/26/2022	NEW	$0
2022	2022	HENRY FORD HEALTH SYSTEM	1 FORD PL	DETROIT	MI	48202	WAYNE	USA	National Center on Sleep Disorders Research	000	1	9/14/2022	NEW	$759,979
														Subtotal = $759,979

Grand Total All Awards = $2,836,997

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Sleep reactivity as a novel mechanism in Shift Work Disorder

Award Number: R01HL160870

ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 09/15/2022

PERIOD OF PERFORMANCE END DATE: 05/31/2026

AWARD TERMINATION DATE: 03/12/2026

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