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| ID | Type | Description | Link |
|---|---|---|---|
| 1R33AG057806 | U.S. NIH Grant/Contract | View source |
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| Name | Class |
|---|---|
| National Institute on Aging (NIA) | NIH |
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| AM (morning) antihypertensive dosing arm or Control arm | Active Comparator | participants will be asked to continue taking their antihypertensive medication within an hour of awakening |
|
| BBTI arm | Experimental | participants will receive the behavioral treatment for insomnia BBTI by the study nurse. Participants will also be asked to take their antihypertensive medication within an hour of awakening |
|
| PM (evening) antihypertensive dosing or Chronotherapy arm | Experimental | participants will be asked to switch their conventional once daily non-diuretic antihypertensive to bedtime |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| BBTI | Behavioral | 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. |
| Measure | Description | Time Frame |
|---|---|---|
| Change in Mean Sleep Time Systolic Blood Pressure Dip Pre- vs Post-intervention | 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 |
| Measure | Description | Time Frame |
|---|---|---|
| Change in Nocturia Frequency Pre- vs Post-intervention | change in nocturia frequency pre- vs post-intervention as determined by 3-day bladder diary completed at both time points | Baseline and at 6 weeks |
| Change in Nocturnal Polyuira Index (NPi) Pre vs Post-intervention |
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Inclusion Criteria:
The study shall include: ambulatory and functionally-independent community-dwelling men and women aged 65+ years, with
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Shachi Tyagi | University of Pittsburgh | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Pittsburgh | Pittsburgh | Pennsylvania | 15213 | United States |
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After the telephone screening, eligible participants were scheduled for the first in-person study visit. No study procedures were performed till informed consent was obtained.
Recruitment started June 2022 through September 2023. 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 University of Pittsburgh Medical Center, Montefiore Hospital located in Pittsburgh, Pennsylvania
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| ID | Title | Description |
|---|---|---|
| FG000 | AM (Morning) Antihypertensive Dosing- Control Arm | participants will be asked to continue taking their antihypertensive medication within an hour of awakening AM antihypertensive dosing: participants will be asked to continue taking their antihypertensive medication within an hour of awakening |
| FG001 | BBTI Arm | participants will receive the brief behavioral treatment for insomnia (BBTI) by the study nurse. Participants will also be asked to take their antihypertensive medication within an hour of awakening 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. |
| FG002 | PM (Evening) Antihypertensive Dosing or Chronotherapy Arm | participants will be asked to switch their conventional once daily non-diuretic antihypertensive to bedtime PM antihypertensive dosing or Chronotherapy: participants will be asked to switch their conventional once daily non-diuretic antihypertensive to bedtime |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
Overall, 30 participants were enrolled, 10 randomized to each of the three study arms
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| ID | Title | Description |
|---|---|---|
| BG000 | AM Antihypertensive Dosing Arm | participants will be asked to continue taking their antihypertensive medication within an hour of awakening AM antihypertensive dosing: participants will be asked to continue taking their antihypertensive medication within an hour of awakening |
| BG001 | BBTI Arm |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Change in Mean Sleep Time Systolic Blood Pressure Dip Pre- vs Post-intervention | 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 | Posted | Mean | Standard Deviation | percentage of daytime mean SBP | Baseline and at 6 weeks |
|
Adverse event data was collected over the duration of study participation for each participant, 6 weeks
All participants continued to take medications that were prescribed by their outpatient providers. No dose adjustments were made either. Therefore, there was no increased risk of mortality or serious adverse events related to the study.
We did collect adverse events were noted by self-report from participants. Specific worsening of any sleep related issues, or any falls during the study period were specifically asked during the telephonic follow-up every 2 visits following randomization.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | AM Antihypertensive Dosing Arm | participants will be asked to continue taking their antihypertensive medication within an hour of awakening AM antihypertensive dosing: participants will be asked to continue taking their antihypertensive medication within an hour of awakening |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Shachi Tyagi, MD, MS | University of Pittsburgh | 4126471274 | sht55@pitt.edu |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Sep 1, 2021 | Nov 21, 2024 | Prot_SAP_000.pdf |
| ICF | No | No | Yes | Informed Consent Form | May 15, 2023 | Nov 21, 2024 | ICF_001.pdf |
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| ID | Term |
|---|---|
| D053158 | Nocturia |
| D006973 | Hypertension |
| D020447 | Parasomnias |
| ID | Term |
|---|---|
| D059411 | Lower Urinary Tract Symptoms |
| D020924 | Urological Manifestations |
| D012816 | Signs and Symptoms |
| D013568 | Pathological Conditions, Signs and Symptoms |
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| ID | Term |
|---|---|
| D019454 | Chronotherapy |
| ID | Term |
|---|---|
| D013812 | Therapeutics |
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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.
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The randomization envelopes will be prepared by the study statistician. Randomization and the intervention BBTI will be completed by research nurse and PI and the outcome assessor will be blinded to randomization.
|
| PM antihypertensive dosing or Chronotherapy | Other | participants will be asked to switch their conventional once daily non-diuretic antihypertensive to bedtime |
|
| AM antihypertensive dosing | Other | participants will be asked to continue taking their antihypertensive medication within an hour of awakening |
|
NPi is calculated using nighttime and daytime urine volumes as reported in 3-day bladder diary as follows: NPi=(nocturnal urine volume/24-hour volume)*100 |
| Baseline and at 6 weeks |
| Change in Global Pittsburgh Sleep Quality Index (PSQI) Score Pre- vs Post-intervention | 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 and negative change indicates sleep improvement. | Baseline and at 6 weeks |
| Change in Sleep Efficiency Pre- vs Post-intervention | 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 |
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 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. |
| BG002 | PM Antihypertensive Dosing or Chronotherapy Arm | participants will be asked to switch their conventional once daily non-diuretic antihypertensive to bedtime PM antihypertensive dosing or Chronotherapy: participants will be asked to switch their conventional once daily non-diuretic antihypertensive to bedtime |
| BG003 | Total | Total of all reporting groups |
| Participants |
|
| Age, Continuous | Mean | Standard Deviation | years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Participants enrolled lived in or near the city of Pittsburgh, PA | Number | participants |
|
| Office systolic blood pressure | Mean | Standard Deviation | mm Hg |
|
| Office diastolic blood pressure | Mean | Standard Deviation | mm Hg |
|
| Office heart rate | Mean | Standard Deviation | beats per minute |
|
| Body mass index (BMI) | Mean | Standard Deviation | kg/m2 |
|
| Post void residual | Mean | Standard Deviation | ml |
|
| Calcium channel blocker | Count of Participants | Participants |
|
| Beta-blocker | Count of Participants | Participants |
|
| Angiotensin converting enzyme inhibitor/ Angiotensin receptor blocker | Count of Participants | Participants |
|
| Thiazide diuretic | Count of Participants | Participants |
|
| Loop diuretic | Count of Participants | Participants |
|
| Alpha- blocker | Count of Participants | Participants |
|
| Statin | Count of Participants | Participants |
|
| Antidepressant | Count of Participants | Participants |
|
| Nonsteroidal anti-inflammatory drugs (NSAIDs) | Count of Participants | Participants |
|
| Antimuscarinic | Count of Participants | Participants |
|
| oral hypoglycemic | Count of Participants | Participants |
|
| Insulin | Count of Participants | Participants |
|
| Hypnotic | Count of Participants | Participants |
|
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 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. |
| OG002 | PM Antihypertensive Dosing or Chronotherapy Arm | participants will be asked to switch their conventional once daily non-diuretic antihypertensive to bedtime PM antihypertensive dosing or Chronotherapy: participants will be asked to switch their conventional once daily non-diuretic antihypertensive to bedtime |
|
|
|
| Secondary | Change in Nocturia Frequency Pre- vs Post-intervention | change in nocturia frequency pre- vs post-intervention as determined by 3-day bladder diary completed at both time points | Posted | Mean | Standard Deviation | number of episodes | Baseline and at 6 weeks |
|
|
|
|
| Secondary | Change in Nocturnal Polyuira Index (NPi) Pre vs Post-intervention | NPi is calculated using nighttime and daytime urine volumes as reported in 3-day bladder diary as follows: NPi=(nocturnal urine volume/24-hour volume)*100 | Posted | Mean | Standard Deviation | % of 24h urine output excreted at night | Baseline and at 6 weeks |
|
|
|
|
| Secondary | Change in Global Pittsburgh Sleep Quality Index (PSQI) Score Pre- vs Post-intervention | 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 and negative change indicates sleep improvement. | Posted | Mean | Standard Deviation | score on a scale | Baseline and at 6 weeks |
|
|
|
|
| Secondary | Change in Sleep Efficiency Pre- vs Post-intervention | 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 | Posted | Mean | Standard Deviation | %: (total sleep time/time in bed)*100 | Baseline and at 6 weeks |
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|
|
|
| 0 |
| 10 |
| 0 |
| 10 |
| 0 |
| 10 |
| EG001 | 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 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. | 0 | 10 | 0 | 10 | 0 | 10 |
| EG002 | PM Antihypertensive Dosing or Chronotherapy Arm | participants will be asked to switch their conventional once daily non-diuretic antihypertensive to bedtime PM antihypertensive dosing or Chronotherapy: participants will be asked to switch their conventional once daily non-diuretic antihypertensive to bedtime | 0 | 10 | 0 | 10 | 0 | 10 |
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| D014652 | Vascular Diseases |
| D002318 | Cardiovascular Diseases |
| D012893 | Sleep Wake Disorders |
| D009422 | Nervous System Diseases |
| D001523 | Mental Disorders |