SHADES Mechanistic Trial

NCT ID: NCT06041581

Last Updated: 2025-07-14

Basic Information

• Recruitment Status: ENROLLING_BY_INVITATION
• Clinical Phase: NA
• Total Enrollment: 200 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-04-25
• Study Completion Date: 2027-07-31

Brief Summary

Cardiovascular disease (CVD) is common, deadly, and costly, and adults with insomnia represent a large group of people at elevated risk of developing CVD in the future. This clinical trial will determine if our updated insomnia treatment, called the SHADES intervention, improves CVD factors thought to explain how insomnia promotes CVD and if these improvements are due to positive changes in sleep factors. A total of 200 primary care patients with insomnia and CVD risk factors will be randomized to 6 months of the SHADES intervention (internet, telephonic, and/or face-to-face cognitive-behavioral therapy for insomnia) or the active control condition (sleep education/hygiene, symptom monitoring, and primary care for insomnia). Before and after treatment, participants will complete measurements of the CVD factors (systemic inflammation, autonomic dysfunction, metabolic dysregulation, proinflammatory gene expression) and the sleep factors (insomnia symptoms, sleep onset latency, wake after sleep onset, sleep efficiency). Researchers will test whether the SHADES intervention produces greater improvements in the CVD factors than the active control condition.

Detailed Description

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. 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 the mechanisms of action of cognitive-behavioral therapy for insomnia (CBT-I), both of which are presently unknown. Therefore, we are conducting a mechanistic trial of 200 primary care patients (45% minority) with insomnia and CVD risk factors but no clinical CVD. Participants will be randomized to 6 months of the SHADES (Strengthening Hearts by Addressing DisruptEd Sleep) intervention or the active control condition. The SHADES intervention is our modernized collaborative care intervention consisting of well-established internet, telephonic, and/or face-to-face CBT-I. The active control condition 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; Exploratory Aim: explore the effect of the SHADES intervention on proinflammatory gene expression. This trial could generate the critical support for the mechanistic rationale and conceptual framework needed to justify the next-step phase III, multi-site clinical trial to determine the SHADES Intervention effect on CVD clinical outcomes, endpoints of great public health relevance, morbidity, and cost.

Conditions

Insomnia; Insomnia Chronic; Insomnia, Primary; Sleep Disturbance; Sleep Disorder; Cardiovascular Diseases; Heart Diseases; Coronary Artery Disease; Stroke; Autonomic Dysfunction; Systemic Inflammatory Response; Metabolic Disease

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: SINGLE

Study Groups

SHADES Intervention

The SHADES intervention is a 6-month, modernized, collaborative care intervention in which a multidisciplinary team delivers established insomnia treatments consistent with patient preference. It uses a stepped, flexible, treat-to-target approach that harnesses technology to maximize access to and convenience of effective treatments and to minimize personnel, training, and space requirements. Our Intervention Team consists of an insomnia clinical specialist, a clinical behavioral sleep medicine and CBT-I delivery expert, a sleep research/medicine expert, and the patients' primary care providers. Treatments to be delivered are CBT-I in different modalities - internet, phone, and face-to-face - all of which are empirically supported.

Group Type: EXPERIMENTAL

Sleep Healthy Using The Internet (SHUTi)

Intervention Type: BEHAVIORAL

Sleep Healthy Using The Internet (SHUTi) is an empirically supported internet intervention. It uses a fully automated, interactive, multimedia format to deliver six 45-minute sessions, the structure and content of which mirror face-to-face CBT-I. Session content includes sleep restriction, stimulus control, sleep hygiene, cognitive restructuring, and relapse prevention. Each session has the same structure: objectives, sleep diary and homework review, new intervention material, homework assignment, and summary. SHUTi is enhanced through interactive features, including personalized goal setting, graphical feedback based on inputted symptoms, animations and illustrations to enhance comprehension, quizzes to test user knowledge, patient vignettes, and video-based expert explanation. Patients also receive tailored sleep recommendations and feedback based on the sleep diary data they enter into the program. We provide basic tablet skills training and tablets with data plans when needed.

Telephonic CBT-I

Intervention Type: BEHAVIORAL

Telephonic CBT-I will be delivered by our insomnia clinical specialist following the highly cited treatment manual by Perlis et al. (2005). Sessions will occur weekly for 30-50 minutes. Telephonic CBT-I will be delivered from a central location - the Insomnia Clinical Specialist's office. Telephonic CBT-I has been shown to be acceptable, feasible, and effective, with effect sizes similar to face-to-face CBT-I.

Face-to-Face CBT-I

Intervention Type: BEHAVIORAL

Face-to-face CBT-I will be delivered by our insomnia clinical specialist following the highly cited treatment manual by Perlis et al. (2005). Sessions will occur weekly for 30-50 minutes. Face-to-face CBT-I will be delivered at the Insomnia Clinical Specialist's office. CBT-I is the clear first-line treatment for insomnia.

Active Control

Active Control (AC) consists of sleep education and hygiene (study staff), symptom monitoring (study staff), and usual primary care for insomnia (clinical staff).

Group Type: ACTIVE_COMPARATOR

Active Control: Sleep Education/Hygiene, Symptom Monitoring, and Usual Primary Care

Intervention Type: OTHER

A designated trial research assistant will have two calls with each AC patient - one 45-minute call on insomnia education and one 45-minute call on sleep hygiene practices. The same research assistant will also call AC patients monthly to assess insomnia symptoms and will notify clinical staff to encourage additional care when indicated. AC patients will receive usual primary care for insomnia. The targeted clinics utilize a team care approach for behavioral health issues, as PCPs are supported by behavioral health clinicians and psychiatrists available for brief counseling and medication management. However, there is no routine screening for insomnia, and behavioral treatment for insomnia is typically limited to sleep hygiene practices.

Interventions

Sleep Healthy Using The Internet (SHUTi)

Sleep Healthy Using The Internet (SHUTi) is an empirically supported internet intervention. It uses a fully automated, interactive, multimedia format to deliver six 45-minute sessions, the structure and content of which mirror face-to-face CBT-I. Session content includes sleep restriction, stimulus control, sleep hygiene, cognitive restructuring, and relapse prevention. Each session has the same structure: objectives, sleep diary and homework review, new intervention material, homework assignment, and summary. SHUTi is enhanced through interactive features, including personalized goal setting, graphical feedback based on inputted symptoms, animations and illustrations to enhance comprehension, quizzes to test user knowledge, patient vignettes, and video-based expert explanation. Patients also receive tailored sleep recommendations and feedback based on the sleep diary data they enter into the program. We provide basic tablet skills training and tablets with data plans when needed.

Intervention Type: BEHAVIORAL

Telephonic CBT-I

Telephonic CBT-I will be delivered by our insomnia clinical specialist following the highly cited treatment manual by Perlis et al. (2005). Sessions will occur weekly for 30-50 minutes. Telephonic CBT-I will be delivered from a central location - the Insomnia Clinical Specialist's office. Telephonic CBT-I has been shown to be acceptable, feasible, and effective, with effect sizes similar to face-to-face CBT-I.

Intervention Type: BEHAVIORAL

Face-to-Face CBT-I

Face-to-face CBT-I will be delivered by our insomnia clinical specialist following the highly cited treatment manual by Perlis et al. (2005). Sessions will occur weekly for 30-50 minutes. Face-to-face CBT-I will be delivered at the Insomnia Clinical Specialist's office. CBT-I is the clear first-line treatment for insomnia.

Intervention Type: BEHAVIORAL

Active Control: Sleep Education/Hygiene, Symptom Monitoring, and Usual Primary Care

A designated trial research assistant will have two calls with each AC patient - one 45-minute call on insomnia education and one 45-minute call on sleep hygiene practices. The same research assistant will also call AC patients monthly to assess insomnia symptoms and will notify clinical staff to encourage additional care when indicated. AC patients will receive usual primary care for insomnia. The targeted clinics utilize a team care approach for behavioral health issues, as PCPs are supported by behavioral health clinicians and psychiatrists available for brief counseling and medication management. However, there is no routine screening for insomnia, and behavioral treatment for insomnia is typically limited to sleep hygiene practices.

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

1. Current primary care patient in Eskenazi Health

2. Age ≥40 years

3. Current insomnia disorder: During screening, ResNet assistants will administer the Insomnia Severity Index (ISI), a validated screener in primary care. Patients who have ISI scores ≥10 (97% sensitivity, 64% specificity) and remain eligible after ResNet screening will be called by our Insomnia Clinical Specialist, who will administer the Structured Clinical Interview for DSM-5 Sleep Disorders to confirm insomnia disorder.

4. Elevated CVD risk: Elevated CVD risk will be defined as ≥2 (if 40-59 years) or ≥1 (if 60+ years) of the following risk factors in the Eskenazi Health EHR in the past 5 years: hypertension, hypercholesterolemia, diabetes, or smoking.

Exclusion Criteria

1. History of clinical CVD: a self-reported CVD diagnosis during screening or any of the following in the patient's electronic health record before enrollment: myocardial infarction, unstable angina, coronary artery disease, cerebrovascular disease, heart failure, percutaneous coronary intervention, or coronary artery bypass graft

2. Sleep disorder diagnosis other than insomnia (e.g., sleep apnea)

3. Continuous positive airway pressure (CPAP) use or a STOP-BANG Questionnaire score ≥5, which is indicative of high probability of sleep apnea

4. A schedule requiring a usual bedtime earlier than 8:00pm or later than 2:00am or arising time earlier than 4:00am or later than 10:00am

5. Major inflammatory conditions (HIV/AIDS, chronic kidney disease, systemic inflammatory disease, or active cancer)

6. Current pregnancy

7. Severe cognitive impairment (≥3 errors on a validated 6-item cognitive screen)

8. History of bipolar disorder or psychosis

9. Acute risk of suicide

• Minimum Eligible Age: 40 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Heart, Lung, and Blood Institute (NHLBI)

NIH

Sponsor Role: collaborator

Eskenazi Health

OTHER

Sponsor Role: collaborator

Regenstrief Institute, Inc.

OTHER

Sponsor Role: collaborator

University of Virginia

OTHER

Sponsor Role: collaborator

University of California, Los Angeles

OTHER

Sponsor Role: collaborator

Indiana University

OTHER

Sponsor Role: lead

Responsible Party

Jesse Stewart

Professor of Psychology

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Jesse C Stewart, Ph.D.

Role: PRINCIPAL_INVESTIGATOR

Indiana University

Locations

Department of Psychology, School of Science, IUPUI

Indianapolis, Indiana, United States

Countries

United States

Other Identifiers

R01HL165115

Identifier Type: NIH

Identifier Source: secondary_id

View Link

17650

Identifier Type: -

Identifier Source: org_study_id