# Strengthening Hearts by Addressing DisruptEd Sleep (SHADES) Mechanistic Trial

> **NIH NIH R01** · INDIANA UNIVERSITY INDIANAPOLIS · 2024 · $60,831

## Abstract

7. PROJECT SUMMARY/ABSTRACT
Cardiovascular disease (CVD) affects nearly 1 in 2 U.S. adults, is the #1 killer of men and women, burdens
disadvantaged groups, and has costs greater than any other condition. While these statistics highlight the
importance of CVD prevention, current approaches have only partial effectiveness. This has created a need to
identify new CVD prevention targets, their underlying mechanisms, and effective interventions. Insomnia, its
candidate mechanisms, and insomnia treatment are strong candidates in this regard. Thirty years of evidence
indicates that insomnia is an independent, clinically important, robust, and potentially causal and modifiable
risk factor for CVD. In addition, biologically plausible mechanisms that could explain how insomnia promotes
the development of CVD have been proposed, with the most strongly supported being systemic inflammation,
autonomic dysfunction, and metabolic dysregulation. Our recent RCT of adults with insomnia disorder provides
promising preliminary support for one such candidate mechanism. Adults randomized to cognitive-behavioral
therapy for insomnia (CBT-I), versus education control, had a reduced risk of high C-reactive protein (CRP), an
inflammation marker implicated in the pathophysiology of CVD and predictive of future CVD events, at follow-
up. Because insomnia now receives limited attention in settings where CVD prevention occurs (e.g., primary
care), there is a large cohort of patients with an unaddressed CVD risk factor (insomnia). This status quo and
the strong state of the insomnia-to-CVD science create the current need for a well-powered, mechanistic trial
to elucidate biological mechanisms underlying the insomnia-to-CVD relationship and CBT-I’s mechanisms of
action, both of which are presently unknown. Therefore, we propose a mechanistic trial of 200 primary care
patients (45% minority) with insomnia disorder and CVD risk factors but no clinical CVD. Patients will be
randomized to 6 months of the SHADES (Strengthening Hearts by Addressing DisruptEd Sleep) Intervention or
Active Control. The SHADES Intervention is our modernized collaborative care intervention consisting of well-
established internet, telephonic, and face-to-face CBT-I. Active Control consists of sleep education/hygiene,
symptom monitoring, and primary care for insomnia. Our proposal has four aims – Aim 1: determine the effect
of the SHADES Intervention on our primary CVD mechanism of high-sensitivity CRP; Aim 2: determine the
effect of the SHADES Intervention on our secondary CVD mechanisms of systemic inflammation, autonomic
dysfunction, and metabolic dysregulation; Aim 3: examine if 6-month improvements in upstream sleep
mechanisms mediate the SHADES Intervention effect on 6-month improvements in downstream CVD
mechanisms; ExploratoryAim: explore the effect of the SHADES intervention on proinflammatory gene
expression. The proposed trial would generate the critical support for the mechanistic rationale a...

## Key facts

- **NIH application ID:** 11160058
- **Project number:** 3R01HL165115-02S1
- **Recipient organization:** INDIANA UNIVERSITY INDIANAPOLIS
- **Principal Investigator:** Jesse C Stewart
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $60,831
- **Award type:** 3
- **Project period:** 2023-08-15 → 2025-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11160058

## Citation

> US National Institutes of Health, RePORTER application 11160058, Strengthening Hearts by Addressing DisruptEd Sleep (SHADES) Mechanistic Trial (3R01HL165115-02S1). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/11160058. Licensed CC0.

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