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Hypnotic Resistance: Definitions, Prevalence, and Risk Factors

Award Number: R21HL181601
ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 08/15/2026
PERIOD OF PERFORMANCE END DATE: 07/31/2028

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Hypnotic Resistance: Definitions, Prevalence, and Risk Factors - ABSTRACT Insomnia is a highly prevalent sleep disorder associated with substantial morbidity and economic burden. While cognitive behavioral therapy for insomnia (CBT-I) is recommended as first-line treatment, hypnotic medications are commonly used due to limited availability of CBT-I. However, a significant proportion of individuals do not respond adequately to hypnotics, leading to treatment-resistant insomnia (TRI). This project aims to address critical knowledge gaps related to TRI prevalence, risk factors, and genetic underpinnings. Aim 1 focuses on defining and quantifying TRI prevalence in a real-world clinical sample. Using electronic health record (EHR) data from the Mayo Clinic Biobank (MCB) and Mayo Clinic Tapestry Project we will refine TRI definitions and estimate prevalence rates. Chart review will validate these definitions, enhancing diagnostic accuracy. Aim 2 seeks to identify clinical and demographic risk factors associated with TRI and construct a predictive clinical risk model. Leveraging structured EHR data, phenotype-based phenome-wide association studies (PheWAS) will uncover correlations between TRI and comorbidities. Machine learning algorithms will then develop and internally validate a predictive model for TRI. Aim 3 investigates the genetic architecture of TRI and its causal associations. Genome-wide association studies (GWAS) within each biobank, followed by meta-analysis, will identify TRI-associated genetic variants. Sex- stratified analyses and polygenic score (PGS) modeling will explore sex-specific effects and predictive power of genetic risk scores. Overall, this project will provide comprehensive insights into TRI, facilitating the development of individualized treatment strategies and guiding future large-scale studies.


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 = $242,100 )
2026	2026	MAYO CLINIC	200 1ST ST SW	ROCHESTER	MN	55905	OLMSTED	USA	National Center on Sleep Disorders Research	000	1	8/10/2026	NEW	$242,100
														Subtotal = $242,100

Grand Total All Awards = $242,100

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Hypnotic Resistance: Definitions, Prevalence, and Risk Factors

Award Number: R21HL181601

ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 08/15/2026

PERIOD OF PERFORMANCE END DATE: 07/31/2028

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