An interventional study of BBTI and PM antihypertensive dosing or Chronotherapy in Nocturia, Hypertension and Sleep Disturbance, sponsored by University of Pittsburgh. Completed at 1 site in United States. Open to participants aged 65 Years and older. Per ClinicalTrials.gov, last updated 2024-12-17.
Sponsored by University of Pittsburgh · Not applicable, Interventional, and Other
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.
134 studies on the registry are indexed under Nocturia; 22 are open to participants now.
This study's enrollment of 30 is below the median of 71 across 108 interventional studies indexed under Nocturia.
Browse Nocturia studies →University of Pittsburgh is the lead sponsor of 1,419 studies on the registry; 168 are open to participants now.
Of its 9 completed or terminated interventional studies of FDA-regulated products, 4 (44%) have results posted.
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Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
The study shall include: ambulatory and functionally-independent community-dwelling men and women aged 65+ years, with
Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Short tests of memory and thinking, each scored out of 30. Lower scores suggest more difficulty; criteria give a range, either to include people with memory problems or to leave them out.
GFR (glomerular filtration rate) is how much blood the kidneys filter each minute. It is usually estimated from a blood test — eGFR, by formulas such as CKD-EPI or MDRD — and some studies ask for it to be measured directly instead. Usually given in mL/min/1.73 m².
Check the method, the units and the minimum the study states. A value of 90 or above is in the normal-or-high range, but kidney damage can show in other tests too.
MMSE and MoCA
Short tests of memory and thinking, each scored out of 30. Lower scores suggest more difficulty; criteria give a range, either to include people with memory problems or to leave them out.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
GFR and eGFR (kidney filtering)
GFR (glomerular filtration rate) is how much blood the kidneys filter each minute. It is usually estimated from a blood test — eGFR, by formulas such as CKD-EPI or MDRD — and some studies ask for it to be measured directly instead. Usually given in mL/min/1.73 m².
Check the method, the units and the minimum the study states. A value of 90 or above is in the normal-or-high range, but kidney damage can show in other tests too.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
participants will be asked to continue taking their antihypertensive medication within an hour of awakening
Other: AM antihypertensive dosing
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
Behavioral: BBTI
participants will be asked to switch their conventional once daily non-diuretic antihypertensive to bedtime
Other: PM antihypertensive dosing or Chronotherapy
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.
participants will be asked to switch their conventional once daily non-diuretic antihypertensive to bedtime
participants will be asked to continue taking their antihypertensive medication within an hour of awakening
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
Time frame: Baseline and at 6 weeks
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
Time frame: Baseline and at 6 weeks
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
Time frame: 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.
Time frame: 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
Time frame: Baseline and at 6 weeks
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
| Milestone | AM (Morning) Antihypertensive Dosing- Control Arm | BBTI Arm | PM (Evening) Antihypertensive Dosing or Chronotherapy Arm |
|---|---|---|---|
| Started | 10 | 10 | 10 |
| Completed | 10 | 10 | 10 |
| Not completed | 0 | 0 | 0 |
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
| percentage of daytime mean SBP | AM Antihypertensive Dosing Arm | BBTI Arm | PM Antihypertensive Dosing or Chronotherapy Arm |
|---|---|---|---|
| Change in Mean Sleep Time Systolic Blood Pressure Dip Pre- vs Post-intervention | -0.4 ± 7.9 | 7.3 ± 13.5 | 3.9 ± 10.0 |
change in nocturia frequency pre- vs post-intervention as determined by 3-day bladder diary completed at both time points
| number of episodes | AM Antihypertensive Dosing Arm | BBTI Arm | PM Antihypertensive Dosing or Chronotherapy Arm |
|---|---|---|---|
| Change in Nocturia Frequency Pre- vs Post-intervention | -0.3 ± 1.0 | -0.6 ± 0.7 | -0.3 ± 0.8 |
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
| % of 24h urine output excreted at night | AM Antihypertensive Dosing Arm | BBTI Arm | PM Antihypertensive Dosing or Chronotherapy Arm |
|---|---|---|---|
| Change in Nocturnal Polyuira Index (NPi) Pre vs Post-intervention | 0.5 ± 7.4 | -6.0 ± 9.7 | -0.9 ± 7.6 |
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.
| score on a scale | AM Antihypertensive Dosing Arm | BBTI Arm | PM Antihypertensive Dosing or Chronotherapy Arm |
|---|---|---|---|
| Change in Global Pittsburgh Sleep Quality Index (PSQI) Score Pre- vs Post-intervention | 0.5 ± 2.9 | -1.4 ± 2.2 | -1.2 ± 3.7 |
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
| %: (total sleep time/time in bed)*100 | AM Antihypertensive Dosing Arm | BBTI Arm | PM Antihypertensive Dosing or Chronotherapy Arm |
|---|---|---|---|
| Change in Sleep Efficiency Pre- vs Post-intervention | -7 ± 15.3 | 12 ± 7.8 | -3 ± 11.8 |
Collected over Adverse event data was collected over the duration of study participation for each participant, 6 weeks. Non-serious events are listed at a 0% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| AM Antihypertensive Dosing Arm | 0/10 (0%) | 0/10 (0%) | 0/10 (0%) |
| BBTI Arm | 0/10 (0%) | 0/10 (0%) | 0/10 (0%) |
| PM Antihypertensive Dosing or Chronotherapy Arm | 0/10 (0%) | 0/10 (0%) | 0/10 (0%) |
Overall, 30 participants were enrolled, 10 randomized to each of the three study arms
| Age, Categorical(Participants) | AM Antihypertensive Dosing Arm | BBTI Arm | PM Antihypertensive Dosing or Chronotherapy Arm | Total |
|---|---|---|---|---|
| <=18 years | 0 | 0 | 0 | 0 |
| Between 18 and 65 years | 0 | 0 | 0 | 0 |
| >=65 years | 10 | 10 | 10 | 30 |
| Age, Continuous(years) | AM Antihypertensive Dosing Arm | BBTI Arm | PM Antihypertensive Dosing or Chronotherapy Arm | Total |
|---|---|---|---|---|
| Mean | 73.9 ± 5 | 69.4 ± 4.6 | 71.5 ± 4.2 | 71.6 ± 4.8 |
| Sex: Female, Male(Participants) | AM Antihypertensive Dosing Arm | BBTI Arm | PM Antihypertensive Dosing or Chronotherapy Arm | Total |
|---|---|---|---|---|
| Female | 4 | 7 | 6 | 17 |
| Male | 6 | 3 | 4 | 13 |
| Race (NIH/OMB)(Participants) | AM Antihypertensive Dosing Arm | BBTI Arm | PM Antihypertensive Dosing or Chronotherapy Arm | Total |
|---|---|---|---|---|
| American Indian or Alaska Native | 0 | 0 | 0 | 0 |
| Asian | 0 | 0 | 0 | 0 |
| Native Hawaiian or Other Pacific Islander | 0 | 0 | 0 | 0 |
| Black or African American | 1 | 3 | 0 | 4 |
| White | 9 | 7 | 10 | 26 |
| More than one race | 0 | 0 | 0 | 0 |
| Unknown or Not Reported | 0 | 0 | 0 | 0 |
| Region of Enrollment(participants) | AM Antihypertensive Dosing Arm | BBTI Arm | PM Antihypertensive Dosing or Chronotherapy Arm | Total |
|---|---|---|---|---|
| United States | 10 | 10 | 10 | 30 |
| Office systolic blood pressure(mm Hg) | AM Antihypertensive Dosing Arm | BBTI Arm | PM Antihypertensive Dosing or Chronotherapy Arm | Total |
|---|---|---|---|---|
| Mean | 144.9 ± 13.3 | 137.4 ± 9.5 | 155.5 ± 14.6 | 145.8 ± 12.5 |
| Office diastolic blood pressure(mm Hg) | AM Antihypertensive Dosing Arm | BBTI Arm | PM Antihypertensive Dosing or Chronotherapy Arm | Total |
|---|---|---|---|---|
| Mean | 80.4 ± 8.3 | 79.9 ± 11 | 85.7 ± 11.7 | 82 ± 10.5 |
| Office heart rate(beats per minute) | AM Antihypertensive Dosing Arm | BBTI Arm | PM Antihypertensive Dosing or Chronotherapy Arm | Total |
|---|---|---|---|---|
| Mean | 66.5 ± 13.4 | 63.6 ± 8.7 | 68.5 ± 8.9 | 66.2 ± 10.4 |
15 further baseline measures are reported on the registry.
PDFs hosted by the registry, ClinicalTrials.gov.
Plan to share: No
Ran from Jun 2022 to primary completion in Nov 2023, 17 months.
Results were first posted in Dec 2024, 1 year after primary completion.
Of 34 interventional studies with no phase under Nocturia, half reached primary completion within 17 months of starting (the median), counting those still running; a quarter within 7 and three quarters within 37. This study's 17 months is close to that.
How these figures are worked out, and which studies are left out of them.
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