Sleep Quality and Mechanisms of Cardiovascular Risks in Adults With Hypertension

The investigators propose to utilize a behavioral intervention to manipulate sleep quality in 150 adults with hypertension and comorbid insomnia, who will receive a 6-week Cognitive Behavioral therapy for Insomnia (CBT-I) intervention, which has been shown to markedly improve sleep quality and promote consolidated sleep in approximately 60% of those treated. A lowering of nighttime blood pressure is one of several proposed mechanisms to be examined.

• Cognitive Behavioral Therapy for Insomnia (CBT-I) (Behavioral): 6-week CBT-I therapy to help improve sleep quality

Primary outcomes

• Change in Blood Pressure During the Nighttime Sleep Period [Baseline, 6 months post-intervention]: Average nighttime blood pressure measured before CBT-I (Cognitive Behavioral Therapy for Insomnia) (baseline) and after CBT-I (6 months post-intervention).
• Change in Sleep During the Nighttime Sleep Period as Measured by Sleep Diary [Baseline, 6 months post-intervention]: Sleep efficiency (percent-time asleep during the sleep period) measured before CBT-I (Cognitive Behavioral Therapy for Insomnia) (baseline) and after CBT-I (6 months post-intervention).
• Change in Sleep During the Nighttime Sleep Period as Measured by Actigraphy [Baseline, 6 months post-intervention]: Sleep efficiency (percent-time asleep during the sleep period) measured by actigraphy before CBT-I (Cognitive Behavioral Therapy for Insomnia) (baseline) and after CBT-I (6 months post-intervention).
• Changes in Insomnia Severity as Measured by the Insomnia Severity Index (ISI) [Baseline, 6 months post-intervention]: The ISI is a seven-item questionnaire where respondents rate each element using Likert-type scales. Responses can range from 0 to 4 and are summed for a total score range of 0 to 28, where higher scores indicate more acute symptoms of insomnia.

Secondary outcomes

• Change in Awake Blood Pressure [Baseline, 6 months post-intervention]: Average awake blood pressure (mm Hg) measured by 24 hour ambulatory blood pressure monitoring before CBT-I (Cognitive Behavioral Therapy for Insomnia) (baseline) and after CBT-I (6 months post-intervention).
• Change in Nighttime Blood Pressure Dip Percentage [Baseline, 6 months post-intervention]: Average percent change in blood pressure before CBT-I (Cognitive Behavioral Therapy for Insomnia) (baseline) and after CBT-I (6 months post-intervention).
• Change in Vascular Endothelial Function [Baseline, 6 months post-intervention]: Percent dilation of the brachial artery to reactive hyperemia measured by flow mediated dilation before CBT-I (Cognitive Behavioral Therapy for Insomnia) (baseline) and after CBT-I (6 months post-intervention).
• Change in Arterial Stiffness [Baseline, 6 months post-intervention]: Pulse wave velocity (m/s) of the descending aorta measured using the Complior system before CBT-I (Cognitive Behavioral Therapy for Insomnia) (baseline) and after CBT-I (6 months post-intervention).
• Change in Lipid Profile - HDL (High-Density Lipoprotein), LDL (Low-Density Lipoprotein), and Triglycerides [Baseline, 6 months post-intervention]: Lipids (HDL, LDL, and Triglycerides) from fasting venous blood draw measured before CBT-I (Cognitive Behavioral Therapy for Insomnia) (baseline) and after CBT-I (6 months post-intervention).
• Change in Nighttime Sympathetic Nervous System Activity [Pre-CBT-I Baseline (6 weeks) to post-CBT-I (12 weeks)]: Measured by 24 hour urine collection (awake and sleep period collection separated) assayed for catecholamines (epinephrine, norepinephrine) before and after CBT-I. Adjusted via creatinine normalization by dividing by the urine creatinine concentration.
• Change in Sleep Fragmentation During the Nighttime Sleep Period [Baseline, 6 weeks post-intervention]: Sleep Fragmentation Index (SFI) measured by actigraphy before CBT-I (Cognitive Behavioral Therapy for Insomnia) (baseline) and after CBT-I (6 weeks post-intervention). The SFI measures how often sleep is interrupted by brief awakenings or shifts between sleep stages, calculated by dividing the number of these transitions by total sleep time
• Change in Subjective Sleep Quality [Pre-CBT-I baseline (6 week) to post-CBT-I (12 weeks)]: Subjective Sleep Quality measured by Pittsburgh Sleep Quality Index (PSQI) before and after CBT-I. The PSQI is a widely used, self-report questionnaire that assesses sleep quality and disturbances over a one-month period, identifying factors like sleep latency (time to fall asleep), duration, disturbances, medication use, and daytime dysfunction, yielding a global score (0-21) where higher scores indicate poorer sleep.
• Change in Clinic Blood Pressure [Baseline to 6 months post-intervention]: Average office seated blood pressure taken by automated clinic blood pressure monitor after 5 minutes rest and based on the average of 3 readings taken at one minute intervals (mm Hg)

Other outcomes

• Change in Cardiac Function [6 week, 6 months post intervention]: Cardiac left ventricular strain (%) before and after CBT-I
• Change in Cardiac Structure [6 week, 6 months post intervention]: Cardiac left ventricular mass (g m\^-2.7) before and after CBT-I

Sex: All, ages: 30 Years to 60 Years

Inclusion Criteria:

* Systolic BP ≥ 130 mm Hg based upon two standardized BP screening assessments
* A current diagnosis of insomnia disorder as defined in the International Classification of Sleep Disorders (ICSD-3); or undiagnosed, but suspected, insomnia disorder that is confirmed at their screening lab visit

Exclusion Criteria:

* Uncontrolled hypertension (screening office BP > 160/100 mm Hg)
* Antihypertensive medication use
* Cardiovascular medications
* Previously diagnosed moderate or severe obstructive sleep apnea
* Severe obesity defined by BMI>40 kg/m2
* Pacemakers
* Atrial fibrillation
* Acute coronary syndrome or coronary revascularization procedure within 6 months of enrollment
* Congestive heart failure
* Identifiable cause of hypertension (e.g., primary hyperaldosteronism, renal artery stenosis, untreated hyper- or hypothyroidism, chronic kidney disease, Cushing's disease, pheochromocytoma, coarctation of the aorta)
* Severe uncorrected valvular heart disease
* Current pregnancy
* Active diagnosis of psychosis, bipolar disorder
* Diabetes
* Severely impaired hearing or speech
* Participation in another interventional study to address insomnia
* Rotating shift workers
* Prominent suicidal or homicidal ideation (as assessed through a clinical interview)
* Psychiatric Hospitalization within the past 12 months
* Alcohol or drug abuse within 12 months
* Exposure-based PTSD treatment
* Dementia
* Unstable comorbid sleep disorder requiring assessment and/or treatment outside of the study protocol
* Medical or psychiatric conditions judged to be the primary cause of insomnia
* Inability to comply with the assessment procedures or inability to provide informed consent.

Participant flow

Outcome results

• Change in Blood Pressure During the Nighttime Sleep Period (Primary), Mean, mmHg: Cognitive Behavioral Therapy for Insomnia -2.48 (-4.20 to -0.70) (p 0.002)
• Change in Sleep During the Nighttime Sleep Period as Measured by Sleep Diary (Primary), Mean, percentage of time asleep: Cognitive Behavioral Therapy for Insomnia 6.9 (6.2 to 7.6) (p <0.001)
• Change in Sleep During the Nighttime Sleep Period as Measured by Actigraphy (Primary), Mean, percentage of time asleep: Cognitive Behavioral Therapy for Insomnia 1.4 (-0.6 to 3.5) (p 0.173)
• Changes in Insomnia Severity as Measured by the Insomnia Severity Index (ISI) (Primary), Mean, score on a scale: Cognitive Behavioral Therapy for Insomnia -7.9 (-8.8 to -7.0) (p <0.001)
• Change in Awake Blood Pressure (Secondary), Mean, mmHg: Cognitive Behavioral Therapy for Insomnia -1.38 (-2.60 to -0.20) (p 0.024)
• Change in Nighttime Blood Pressure Dip Percentage (Secondary), Mean, percentage points: Cognitive Behavioral Therapy for Insomnia 0.90 (0.10 to 1.70) (p 0.208)
• Change in Vascular Endothelial Function (Secondary), Mean, percentage of dilation: Cognitive Behavioral Therapy for Insomnia 1.41 (0.57 to 2.26) (p 0.001)
• Change in Arterial Stiffness (Secondary), Mean, m/s: Cognitive Behavioral Therapy for Insomnia 0.09 (-0.28 to 0.10) (p -0.365)
• Change in Lipid Profile - HDL (High-Density Lipoprotein), LDL (Low-Density Lipoprotein), and Triglycerides (Secondary), Mean, mg/dL: Cognitive Behavioral Therapy for Insomnia -1.82 (-3.40 to -0.24) (p 0.024)
• Change in Nighttime Sympathetic Nervous System Activity (Secondary), Mean, micrograms/mg creatinine: Cognitive Behavioral Therapy for Insomnia 0.01 (-0.04 to 0.06) (p 0.644)
• Change in Sleep Fragmentation During the Nighttime Sleep Period (Secondary), Mean, transitions/hour: Cognitive Behavioral Therapy for Insomnia -1.60 (-5.50 to 2.30) (p 0.044)
• Change in Subjective Sleep Quality (Secondary), Mean, score on a scale: Cognitive Behavioral Therapy for Insomnia -3.53 (-4.08 to -2.99)
• Change in Clinic Blood Pressure (Secondary), Mean, mmHg: Cognitive Behavioral Therapy for Insomnia -1.75 (-3.60 to 0.10) (p 0.024)
• Change in Cardiac Function (Other pre specified)
• Change in Cardiac Structure (Other pre specified)

Adverse events

Time frame: Up to 6 months post-intervention

• Results publication: Sherwood A, Ulmer C, Wu JQ, Blumenthal JA, Herold E, Smith PJ, Koch GG, Johnson K, Viera A, Edinger J, Hinderliter A. Cognitive behavior therapy for insomnia for untreated hypertension with comorbid insomnia disorder: The SLEEPRIGHT clinical trial. J Clin Hypertens (Greenwich). 2024 Apr;26(4):441-447. doi: 10.1111/jch.14763. Epub 2024 Mar 11. PMID 38468418

• Study Protocol and Statistical Analysis Plan (PDF, 2023-11-29)
• Informed Consent Form (PDF, 2021-03-23)

• Andrew Sherwood, PhD, Principal investigator, Duke University