Clinical trial NCT06041581: SHADES Mechanistic Trial
Official title: Strengthening Hearts by Addressing DisruptEd Sleep (SHADES) Mechanistic Trial
Study type: INTERVENTIONAL
Overall status: ENROLLING_BY_INVITATION
Phase: NA
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
Keywords: Primary Care
Internet Interventions
Cognitive-Behavioral Therapy for Insomnia
Insomnia
Cardiovascular Diseases
Lead sponsor: Indiana University
Sponsor class: OTHER
Collaborators: name: National Heart, Lung, and Blood Institute (NHLBI)
name: Eskenazi Health
name: Regenstrief Institute, Inc.
name: University of Virginia
name: University of California, Los Angeles
First posted: 2023-09-18
Enrollment: 200
Sex: ALL
Minimum age (years): 40
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.

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 are:

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

Primary outcomes:
measure: High-Sensitivity C-Reactive Protein (hsCRP)
timeFrame: Baseline, 6 months
Secondary outcomes:
measure: Interleukin-6 (IL-6)
timeFrame: Baseline, 6 months
measure: Pre-Ejection Period (PEP)
timeFrame: Baseline, 6 months
measure: High-Frequency Heart Rate Variability (HF HRV)
timeFrame: Baseline, 6 months
measure: Hemoglobin A1c (HbA1c)
timeFrame: Baseline, 6 months
measure: Homeostasis Model Assessment of Insulin Resistance (HOMA-IR)
timeFrame: Baseline, 6 months
Other outcomes:
Locations:
city: Indianapolis
country: United States
facility: Department of Psychology, School of Science, IUPUI
state: Indiana
Study officials:
affiliation: Indiana University
name: Jesse C Stewart, Ph.D.
role: PRINCIPAL_INVESTIGATOR
References: