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Impact of Behavioral Treatment of Insomnia on Nighttime Urine Production

Impact of Behavioral Treatment of Insomnia on Nighttime Urine Production

Status
Completed
Phases
NA
Study type
Interventional
Source
ClinicalTrials.gov
Registry ID
NCT03883724
Enrollment
56
Registered
2019-03-21
Start date
2019-02-01
Completion date
2021-11-30
Last updated
2022-12-22

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Nocturia, Nocturnal Enuresis, Poor Quality Sleep, Sleep Fragmentation

Keywords

Nocturia, Poor sleep

Brief summary

Nocturia is prevalent in older adults and it vastly reduces quality of life. Yet its treatment remains inadequate because its causes are not well understood, especially nocturnal polyuria or increased urine production at night. This study, which builds on the investigators' ongoing research, would be the first of its kind to explore the role of sleep in nighttime urine production. The findings will contribute important knowledge to guide development of better targeted and more effective therapy for this prevalent and morbid condition.

Detailed description

Prevalent, morbid, and costly ($61 billion/year in 2012), nocturia is a major problem, especially for older adults. It increases the risk of falls, fractures, depression, nursing home placement, and death. Yet management of nocturia remains inadequate. Most behavior and pharmacotherapies for nocturia focus on bladder-related etiologies, and it's most prevalent attribute nocturnal polyuria (NP), or increased urine production during sleep remains poorly understood and inadequately treated with little advancement over the last 50 years. Disruption of diurnal excretory pattern, with higher nighttime urine production is common in older adults. While studies in young adults show that sleep plays a critical role in regulating nighttime urine production, among older adults the role of poor sleep in NP is under-investigated. Urine production follows a circadian pattern in which transition from wake to sleep is followed by a pronounced decrease in excretion of water, electrolytes and other osmotically active substances. Studies in young population have established that physiological urine production follows a circadian rhythm, which is regulated by diurnal variation in secretion of hormones controlling water and salt excretion such as arginine vasopressin, renin-angiotensin-aldosterone system, and atrial natriuretic peptide. Sleep deprivation blunts nocturnal surge of these hormones and consequently alter water and salt excretion thereby increase nighttime urine volume leading to NP. Recent evidence suggests that poor sleep quality, frequent sleep interruptions especially in the first part of the night and shorter duration of first uninterrupted sleep period are associated with NP but its pathophysiology is not fully understood. Additionally, among older adults with poor sleep, the investigators have shown that a behavioral intervention directed solely towards sleep (BBTI- brief behavioral treatment of insomnia an efficacious multimodal behavioral treatment for insomnia) not only improves sleep, but also nocturia. Hence, the investigators postulate that sleep interruptions in the first part of the sleep impacts the hormonal regulation of nighttime urine production causing NP. In addition, the investigators postulate that interventions to prolong the first uninterrupted sleep period will decrease NP and hence nocturia. The, aims of the present proposal are to: 1) examine the impact of BBTI on duration of the first of uninterrupted sleep period and NP in elderly with nocturia; and 2) establish NP and duration of first uninterrupted sleep as mechanisms by which BBTI impacts nocturia. The investigators' hypothesis is that BBTI improves nocturia not only by improving sleep, (and specifically, duration of the first uninterrupted sleep period), but also by decreasing NP. To accomplish these goals the investigators will recruit 60 community dwelling adults (aged \>65) with nocturia and NP. Sleep will be assessed subjectively with the Insomnia Severity Index and objectively by 7-day sleep diary and wrist actigraph. Concurrently the investigators will collect 3-day bladder diary data to document their voiding pattern and volume during day and night. Participants will be randomized to receive the 4-week behavioral sleep intervention BBTI by a trained therapist or an information control intervention. The participants will repeat the study measures post-intervention. The study results will provide important insights into shared pathological mechanisms underlying poor sleep, nocturia and nighttime urine production.

Interventions

BEHAVIORALBrief behavioral treatment of insomnia (BBTI)

The BBTI consists of a 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. The brief behavioral treatment component will focus on four behaviors that promote sleep through homeostatic, circadian, or association mechanisms. 50 These four interventions are simple to conceptualize and implement, and constitute the core of efficacious multi-modal behavioral treatments for insomnia.

BEHAVIORALInformation-only control (IC)

The IC condition is intended to emulate the behavioral treatment information generally to available patients. It includes instructions to review hand out on healthy sleep practices. We will also use patient education videos on insomnia developed locally and widely used in clinical research. The content of these videos overlap substantially with BBTI but without individualized behavioral instructions. Two weeks later, IC participants will receive a 10-minute follow-up telephone call to encourage continued participation. Participants will be referred to the brochures for specific sleep-related questions.

Sponsors

National Institute on Aging (NIA)
CollaboratorNIH
University of Pittsburgh
Lead SponsorOTHER

Study design

Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
OTHER
Masking
NONE

Intervention model description

Randomized controlled trial

Eligibility

Sex/Gender
ALL
Age
65 Years to No maximum
Healthy volunteers
Yes

Inclusion criteria

* ambulatory and functionally-independent community-dwelling men and women * aged 65 years, or more * with nocturia ≥2/night * poor sleep because of frequent awakenings

Exclusion criteria

* Unstable or acute medical or central nervous system conditions * Untreated, current, severe psychiatric condition * Untreated, current, severe overactive bladder syndrome * Post void residual \> 30ml * Sleep apnea with AHI≥15 * Currently diagnosed and/or treated Obstructive Sleep Apnea, Restless Legs Syndrome, parasomnia * Congestive heart failure, by exam or Beta natriuretic peptide (BNP)\> 30 pmol/L * Chronic kidney disease, stage III-V (eGFR\<50) * \>14 alcohol drinks per week

Design outcomes

Primary

MeasureTime frameDescription
Change in Nocturnal Polyuria Indexchange from baseline nocturnal polyuria index at 4 weeksNocturnal Polyuria Index (NPI) is the percentage of 24-hour urine production excreted at night. It is measured using 3-day bladder diary that participants will complete pre- and post-intervention in which the participants document the time and volume of each void during the day and night for 3 days. NPI is calculated using a) nocturnal urine volume (determined by adding the volume of all voids between the times marked in the bladder diary as going to bed with the intent of sleeping and the first awakening to void. The first void after waking is included in the nighttime urine volume), and b) 24-hour urine volume. NPI is calculated as: nocturnal urine volume /24-hour urine volume

Secondary

MeasureTime frameDescription
Change in Nocturiachange from baseline nocturia episodes each night at 4 weeksNocturia=number of awakenings to void each night
Change in Duration of Uninterrupted SleepChange from baseline duration of uninterrupted sleep at 4 weeksDuration of uninterrupted sleep is the first uninterrupted sleep period before first awakening to void

Countries

United States

Participant flow

Recruitment details

Recruitment started Jan 2019 through April 2021. The initial screening was completed telephonically and once screened eligible, the interested participants underwent study related assessments and procedures at the study research suite - Continence Research Unit at UPMC Montefore Hospital located in Pittsburgh, PA

Pre-assignment details

After the telephone screening, the eligible participants completed a home sleep apnea assessment using device ApneaLink Air that was sent to them via mail with instructions for use at home. Those with AHI≥15 were excluded per study exclusion criteria before the in-person Visit 1 or signing the informed consent.

Participants by arm

ArmCount
Brief Behavioral Treatment for Insomnia
This group will undergo behavioral intervention proven to improve sleep among older adults: brief behavioral treatment for insomnia Brief behavioral treatment of insomnia (BBTI): The BBTI consists of a 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. The brief behavioral treatment component will focus on four behaviors that promote sleep through homeostatic, circadian, or association mechanisms. 50 These four interventions are simple to conceptualize and implement, and constitute the core of efficacious multi-modal behavioral treatments for insomnia.
29
Information-only Control
This group is called information-only control. They will be provided sleep-related information. They will also view a video content of which overlap substantially with BBTI but without individualized behavioral instructions. Information-only control (IC): The IC condition is intended to emulate the behavioral treatment information generally to available patients. It includes instructions to review hand out on healthy sleep practices. We will also use patient education videos on insomnia developed locally and widely used in clinical research. The content of these videos overlap substantially with BBTI but without individualized behavioral instructions. Two weeks later, IC participants will receive a 10-minute follow-up telephone call to encourage continued participation. Participants will be referred to the brochures for specific sleep-related questions.
27
Total56

Baseline characteristics

CharacteristicBrief Behavioral Treatment for InsomniaTotalInformation-only Control
ACE-I/ARB7 Participants12 Participants5 Participants
Age, Categorical
<=18 years
0 Participants0 Participants0 Participants
Age, Categorical
>=65 years
29 Participants56 Participants27 Participants
Age, Categorical
Between 18 and 65 years
0 Participants0 Participants0 Participants
Alpha-blocker4 Participants6 Participants2 Participants
Anti-depressant3 Participants7 Participants4 Participants
Antimuscarinic1 Participants2 Participants1 Participants
Beta-blocker2 Participants9 Participants7 Participants
BMI27.2 kg/m2
STANDARD_DEVIATION 5.7
27.8 kg/m2
STANDARD_DEVIATION 5.4
28.4 kg/m2
STANDARD_DEVIATION 5.1
Calcium channel blocker3 Participants7 Participants4 Participants
Creatinine0.86 mg/dL
STANDARD_DEVIATION 0.21
0.9 mg/dL
STANDARD_DEVIATION 0.2
0.94 mg/dL
STANDARD_DEVIATION 0.23
Loop diuretic2 Participants4 Participants2 Participants
NSAIDS6 Participants10 Participants4 Participants
Post void residual11.6 ml
STANDARD_DEVIATION 18.5
15.2 ml
STANDARD_DEVIATION 24
19.3 ml
STANDARD_DEVIATION 28.8
Proton pump inhibitor/ H2 blocker6 Participants11 Participants5 Participants
Race (NIH/OMB)
American Indian or Alaska Native
0 Participants0 Participants0 Participants
Race (NIH/OMB)
Asian
0 Participants0 Participants0 Participants
Race (NIH/OMB)
Black or African American
3 Participants7 Participants4 Participants
Race (NIH/OMB)
More than one race
0 Participants0 Participants0 Participants
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
0 Participants0 Participants0 Participants
Race (NIH/OMB)
Unknown or Not Reported
0 Participants0 Participants0 Participants
Race (NIH/OMB)
White
26 Participants49 Participants23 Participants
Sex: Female, Male
Female
20 Participants36 Participants16 Participants
Sex: Female, Male
Male
9 Participants20 Participants11 Participants
Thiazide diuretic4 Participants9 Participants5 Participants

Adverse events

Event typeEG000
affected / at risk
EG001
affected / at risk
deaths
Total, all-cause mortality
0 / 290 / 27
other
Total, other adverse events
0 / 290 / 27
serious
Total, serious adverse events
0 / 290 / 27

Outcome results

Primary

Change in Nocturnal Polyuria Index

Nocturnal Polyuria Index (NPI) is the percentage of 24-hour urine production excreted at night. It is measured using 3-day bladder diary that participants will complete pre- and post-intervention in which the participants document the time and volume of each void during the day and night for 3 days. NPI is calculated using a) nocturnal urine volume (determined by adding the volume of all voids between the times marked in the bladder diary as going to bed with the intent of sleeping and the first awakening to void. The first void after waking is included in the nighttime urine volume), and b) 24-hour urine volume. NPI is calculated as: nocturnal urine volume /24-hour urine volume

Time frame: change from baseline nocturnal polyuria index at 4 weeks

ArmMeasureGroupValue (MEAN)Dispersion
Brief Behavioral Treatment for InsomniaChange in Nocturnal Polyuria IndexPre-intervention41.7 percentage of urine volumeStandard Deviation 9.9
Brief Behavioral Treatment for InsomniaChange in Nocturnal Polyuria IndexPost-intervention34.5 percentage of urine volumeStandard Deviation 13
Information-only ControlChange in Nocturnal Polyuria IndexPre-intervention41.7 percentage of urine volumeStandard Deviation 10.1
Information-only ControlChange in Nocturnal Polyuria IndexPost-intervention37.8 percentage of urine volumeStandard Deviation 8.6
Comparison: Change in NPi pre- vs post-intervention comparing between group analysisp-value: 0.3ANCOVA
Secondary

Change in Duration of Uninterrupted Sleep

Duration of uninterrupted sleep is the first uninterrupted sleep period before first awakening to void

Time frame: Change from baseline duration of uninterrupted sleep at 4 weeks

ArmMeasureGroupValue (MEAN)Dispersion
Brief Behavioral Treatment for InsomniaChange in Duration of Uninterrupted SleepPre-intervention174 minutes, imputed from bladder diaryStandard Deviation 53
Brief Behavioral Treatment for InsomniaChange in Duration of Uninterrupted SleepPost-intervention227 minutes, imputed from bladder diaryStandard Deviation 68
Information-only ControlChange in Duration of Uninterrupted SleepPre-intervention188 minutes, imputed from bladder diaryStandard Deviation 53
Information-only ControlChange in Duration of Uninterrupted SleepPost-intervention210 minutes, imputed from bladder diaryStandard Deviation 72
Comparison: between-group analysis was completed comparing of Pre- to Post-Intervention change adjusting for baseline value of the outcomep-value: 0.3ANCOVA
Secondary

Change in Nocturia

Nocturia=number of awakenings to void each night

Time frame: change from baseline nocturia episodes each night at 4 weeks

ArmMeasureGroupValue (MEAN)Dispersion
Brief Behavioral Treatment for InsomniaChange in NocturiaPre-intervention2.3 awakenings, as reported on bladder diaryStandard Deviation 0.6
Brief Behavioral Treatment for InsomniaChange in NocturiaPost-intervention1.3 awakenings, as reported on bladder diaryStandard Deviation 0.6
Information-only ControlChange in NocturiaPre-intervention2.1 awakenings, as reported on bladder diaryStandard Deviation 0.7
Information-only ControlChange in NocturiaPost-intervention1.8 awakenings, as reported on bladder diaryStandard Deviation 0.6
Comparison: Change in nocturia frequency pre- vs post-intervention comparing between group analysisp-value: <0.01ANCOVA

Source: ClinicalTrials.gov · Data processed: Feb 4, 2026