Sleep, Hypertension, and Nocturia: a Multicomponent Approach for Comorbid Illnesses (SHyN)

In this study the investigators target three common and comorbid illnesses among older adults namely nocturia or waking at night to void, poor sleep and hypertension. The aim of this proposal is to test behavioral sleep intervention to improve sleep and nocturia vs switching the time of antihypertensive administration to improve nighttime and in turn daytime blood pressure control.

Study Overview

• Status: Completed
• Conditions: Hypertension; Sleep Disturbance; Nocturia
• Intervention / Treatment: Other: AM antihypertensive dosing; Behavioral: BBTI; Other: PM antihypertensive dosing or Chronotherapy

Detailed Description

The investigators posit that a vicious cycle operates between nocturia, poor sleep, and nighttime HTN. HTN act through the pressure-natriuresis mechanism that links sodium (Na) and BP homeostasis: periodic increases in BP drive compensatory renal excretion of Na (natriuresis) and water (diuresis) to reduce blood volume and BP. Normally, BP and natriuresis declines during sleep, decreasing nighttime urine volume (NUV). Elevated nighttime BP increases nocturnal natriuresis causing an increase in nighttime urine volume and hence, NP: the major etiologic factor for nocturia in the elderly. In a recently completed study (AG050892, PI:Tyagi), it was found that poor sleep blunts the normal nighttime rise in antidiuretic hormone-a potent Na conserving hormone, which leads to nocturnal natriuresis and, as a result, NP. Hence, our model incorporates the effects of poor sleep and nighttime HTN on natriuresis, NP, and nocturia. The investigators postulate that treatments targeted towards these etiologies will help break this vicious cycle.

Traditionally, antihypertensive medications are dosed in the morning targeting daytime BP. However, some research suggests that nighttime BP best predicts risk for major cardiovascular events. Several clinical trials of bedtime dosing of BP medication-chronotherapy- show better nighttime BP control. However, no clinical studies have considered or tested chronotherapy as a treatment for nocturia. With respect to poor sleep, the investigators have shown that brief behavioral treatment of insomnia (BBTI) significantly improves not only sleep but also self-reported nocturia among the elderly. Therefore, the investigators envision a multicomponent approach with chronotherapy (bedtime dosing of certain antihypertensives) and behavioral sleep intervention (BBTI) to concurrently address the prevalent and chronic, mutually exacerbating conditions: nocturia, poor sleep, and HTN. The current proposal aims to collect pilot data for a definitive randomized clinical trial.

In the proposed pilot study 30 community-dwelling older adults (aged >65) who take at ≥1 daily non-diuretic antihypertensive medication, have a mean SBP >135 mm Hg, and awaken ≥2 times nightly to void will be randomly assigned to one of the 3 groups of 10 participants each to 1) morning (am) HTN medication dosing, 2) BBTI with am HTN medication dosing, 3) nighttime non-diuretic HTN medication dosing (chronotherapy) for 6 weeks. At baseline and 6 weeks, participants will undergo 48-hour ambulatory BP monitoring, in-home sleep study, complete a 3-day bladder diary. This protocol will allow the investigators to accomplish following Aims:

Aim1: To assess the feasibility and effect of chronotherapy and BBTI in older adults with multiple comorbidities: HTN and nocturia Hypothesis 1: Chronotherapy and BBTI will be (a) feasible treatment options among comorbid older adults, and (b) nocturia and nighttime urine volume, and (c) nighttime SBP will have a greater decrease in BBTI and chronotherapy groups than usual care.

Aim 2: Assess safety and treatment compliance with chronotherapy. Hypothesis 2: The investigators will assess treatment compliance and also collect data on nocturnal lightheadedness and falls to begin to address the safety of HTN chronotherapy.

• Study Type: Interventional
• Enrollment (Actual): 30
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Shachi Tyagi, MD; Phone Number: 4126471274; Email: sht55@pitt.edu
• Study Contact Backup: Name: Kandy Newell, RN; Phone Number: 4126471270; Email: kln40@pitt.edu

Study Locations

• United States
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15213
      • University of Pittsburgh

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 65 years and older (Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

The study shall include: ambulatory and functionally-independent community-dwelling men and women aged 65+ years, with

1. nocturia ≥2/night, and
2. history of high blood pressure and receives one or more non-diuretic, once daily antihypertensive- angiotensin converting enzyme inhibitor (ACE-I), angiotensin receptor blocker (ARB), calcium channel blocker (CCB), beta blocker

Exclusion Criteria:

1. Unstable or acute medical or central nervous system conditions
2. Untreated, current, severe psychiatric condition
3. Untreated, current, severe overactive bladder syndrome
4. Post void residual > 30ml
5. MOCA <26
6. Currently diagnosed and/or treated Obstructive Sleep Apnea, Restless Legs Syndrome, parasomnia
7. CHF, by exam or NT-proB natriuretic peptide (NT-proBNP)> 30 pmol/L56
8. Chronic kidney disease, stage III-V (eGFR<60)
9. >14 alcohol drinks per week
10. >3 caffeinated drinks (~300mg) per day

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: AM antihypertensive dosing arm; participants will be asked to continue taking their antihypertensive medication within an hour of awakening	Other: AM antihypertensive dosing; participants will be asked to continue taking their antihypertensive medication within an hour of awakening
Experimental: BBTI arm; participants will receive the behavioral treatment for insomnia BBTI by the study RN. Participants will also be asked to take their antihypertensive medication within an hour of awakening	Behavioral: BBTI; Participants randomized to BBTI will receive 45- to 60-minute individual intervention session followed by a 30-minute follow-up session 2 weeks later, and 20-minute telephone calls after 1 and 3 weeks. BBTI will focus on four behaviors that promote sleep and discussion of homeostatic and circadian mechanisms of human sleep regulation. These four interventions are simple to conceptualize and implement, and constitute the core of efficacious multi-modal behavioral treatments for insomnia.
Experimental: PM antihypertensive dosing or Chronotherapy arm; participants will be asked to switch their conventional once daily non-diuretic antihypertensive to bedtime	Other: PM antihypertensive dosing or Chronotherapy; participants will be asked to switch their conventional once daily non-diuretic antihypertensive to bedtime

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean sleep time systolic blood pressure dip	The mean sleep time systolic blood pressure dip will be quantified by calculating the difference between daytime mean systolic pressure and nighttime mean systolic pressure expressed as a percentage of the day value for each participant across the 48-hour recording period comparing baseline and post-intervention	Baseline and at 6 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Nocturia	nocturia frequency per 3-day bladder diary completed by participants comparing baseline and post-intervention	Baseline and at 6 weeks
Pittsburgh Sleep Quality Index (PSQI) score	PSQI is a self-rated questionnaire for evaluating subjective sleep quality. PSQI global scores range from 0-21, with higher scores indicating worse sleep quality.	Baseline and at 6 weeks
Sleep efficiency	Sleep efficiency will be calculated as (total sleep time/time in bed)*100 with time in bed and total sleep times obtained from Zmachine worn by participants pre- and post-intervention	Baseline and at 6 weeks

Collaborators and Investigators

• Sponsor: University of Pittsburgh
• Collaborators: National Institute on Aging (NIA)
• Investigators: Principal Investigator: Shachi Tyagi, University of Pittsburgh

Study record dates

Study Major Dates

• Study Start (Actual): June 1, 2022
• Primary Completion (Actual): November 30, 2023
• Study Completion (Actual): January 30, 2024

Study Registration Dates

• First Submitted: June 10, 2022
• First Submitted That Met QC Criteria: June 10, 2022
• First Posted (Actual): June 15, 2022

Study Record Updates

• Last Update Posted (Actual): March 5, 2024
• Last Update Submitted That Met QC Criteria: March 1, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Cardiovascular Diseases; Vascular Diseases; Nervous System Diseases; Sleep Wake Disorders; Lower Urinary Tract Symptoms; Urological Manifestations; Hypertension; Dyssomnias; Parasomnias; Nocturia; Antihypertensive Agents
• Other Study ID Numbers: STUDY21050132; 1R33AG057806 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No