Clinical trial NCT05419830: Sleep, Hypertension, and Nocturia: a Multicomponent Approach for Comorbid Illnesses
Official title: Sleep, Hypertension, and Nocturia: a Multicomponent Approach for Comorbid Illnesses
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Nocturia
Hypertension
Sleep Disturbance
Lead sponsor: University of Pittsburgh
Sponsor class: OTHER
Collaborators: name: National Institute on Aging (NIA)
First posted: 2022-06-15
Enrollment: 30
Sex: ALL
Minimum age (years): 65
Standard ages: OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: 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.
Primary purpose: OTHER

Brief summary: 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.

Detailed description: The investigators posit that a vicious cycle operates between nocturia, poor sleep, and nighttime hypertension (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 systolic blood pressure (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.

Eligibility criteria: 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. Montreal cognitive assessment (MOCA) \<26
6. Currently diagnosed and/or treated Obstructive Sleep Apnea, Restless Legs Syndrome, parasomnia
7. Congestive heart failure, by exam
8. Chronic kidney disease, stage III-V (eGFR\<60)
9. \>14 alcohol drinks per week
10. \>3 caffeinated drinks (\~300mg) per day

Primary outcomes:
measure: Change in Mean Sleep Time Systolic Blood Pressure Dip Pre- vs Post-intervention
timeFrame: Baseline and at 6 weeks
Secondary outcomes:
measure: Change in Nocturia Frequency Pre- vs Post-intervention
timeFrame: Baseline and at 6 weeks
measure: Change in Nocturnal Polyuira Index (NPi) Pre vs Post-intervention
timeFrame: Baseline and at 6 weeks
measure: Change in Global Pittsburgh Sleep Quality Index (PSQI) Score Pre- vs Post-intervention
timeFrame: Baseline and at 6 weeks
measure: Change in Sleep Efficiency Pre- vs Post-intervention
timeFrame: Baseline and at 6 weeks
Other outcomes:
Locations:
city: Pittsburgh
country: United States
facility: University of Pittsburgh
state: Pennsylvania
Study officials:
affiliation: University of Pittsburgh
name: Shachi Tyagi
role: PRINCIPAL_INVESTIGATOR
References: