Sleep and Circadian Interventions for High Blood Pressure

Recruiting in Palo Alto (17 mi)

Overseen by Saurabh S Thosar, PhD

Age: 18 - 65

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Academic

Recruiting

Sponsor: Oregon Health and Science University

Must be taking: Anti-hypertensive

Must not be taking: Prescription medications

Disqualifiers: Heart failure, Psychological conditions, Sleep disorders, others

No Placebo Group

Trial Summary

What is the purpose of this trial?

This study is a mechanistic clinical trial designed to investigate the effects of the circadian system and sleep on non-dipping blood pressure (BP) in people with hypertension (HTN).

Will I have to stop taking my current medications?

The trial allows participants to continue taking contraceptives and anti-hypertensive medications, so you may not need to stop these. However, other prescription medications are not permitted.

What data supports the effectiveness of the treatment for high blood pressure?

Research suggests that maintaining a regular sleep schedule and improving sleep quality can help lower blood pressure. Studies have shown that better sleep can prevent and treat high blood pressure, as disruptions in sleep can lead to higher blood pressure and increased risk of hypertension. ^{1 2 3 4 5}

Is the sleep and circadian intervention for high blood pressure safe for humans?

The research articles provided do not contain specific safety data for sleep and circadian interventions in humans, but they do discuss the importance of timing in blood pressure management and the potential benefits of aligning treatment with the body's natural rhythms. ^{1 2 4 6 7}

How does the Regularized Sleep Schedule treatment for high blood pressure differ from other treatments?

The Regularized Sleep Schedule treatment is unique because it focuses on maintaining a consistent sleep pattern to help regulate blood pressure, unlike traditional treatments that often involve medication. This approach leverages the natural circadian rhythms (the body's internal clock) to optimize blood pressure control, particularly during nighttime sleep, which is when blood pressure typically declines. ^{1 2 3 8 9}

Research Team

Saurabh S Thosar, PhD

Principal Investigator

Oregon Health and Science University

Eligibility Criteria

This trial is for adults aged 25-64 with a BMI of 18.5-42kg/m2 and hypertension, having an average resting BP between 130/80 mmHg and 160/100 mmHg. Excluded are heavy smokers, recent shift workers, frequent travelers across time zones, those on certain meds or with drug/alcohol issues, pregnant women, individuals with severe cardiovascular or psychological conditions, and those with serious sleep disorders.

Inclusion Criteria

I am between 25 and 64 years old.

Your body mass index (BMI) is between 18.5 and 42.

My average blood pressure is between 130/80 and 160/100.

Exclusion Criteria

You have not used cannabis for 30 days before the study.

I have a severe sleep disorder.

I have no chronic diseases affecting my health outcomes, except for high blood pressure.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

At-home Polysomnography

Participants undergo sleep assessment in their home environment using unattended polysomnography

1-2 nights

1 visit (in-person)

Constant Routine Protocol

Participants complete a 5-day overnight forced desynchrony laboratory protocol to uncover circadian rhythms

5 days

Randomized Crossover Trials

Participants complete Overnight Sleep and Rested Wakefulness trials in randomized order to assess nighttime cardiovascular mechanisms

7 days

Sleep Regularization Trial

Participants adhere to a regular sleep schedule for 2 weeks to assess its impact on 24-hour blood pressure

2 weeks

Follow-up

Participants are monitored for safety and effectiveness after the completion of trials

2-4 weeks

Treatment Details

Interventions

• At-home Polysomnography (Procedure)
• Circadian Protocol (Procedure)
• Overnight Sleep Trial (Procedure)
• Regularized Sleep Schedule (Behavioral Intervention)
• Rested Wakefulness Trial (Procedure)

Trial Overview The study examines how the body's circadian rhythm (24-hour cycle) and sleep quality affect blood pressure in hypertensive patients. Participants will undergo various trials including a Circadian Protocol to assess their natural rhythms, Overnight Sleep Trial monitored by polysomnography at home to evaluate sleep patterns, Rested Wakefulness Trial to observe alertness levels after restful sleep, and adherence to a Regularized Sleep Schedule.

Participant Groups

Group I: Dipping vs non-dipping HTN Experimental Treatment 5 Interventions

Participants will wear an ambulatory blood pressure monitor (SpaceLabs, Inc.) which will take their blood pressure in 20-30-minute intervals for 24-48 hours to determine blood pressure dipping status. All participants in this arm will complete the experiments in this order: 1. At-home polysomnography; 2. Constant Routine protocol; 3. Rested Wakefulness Trial AND Overnight Sleep Trial (Randomized crossover); 4. Sleep Regularization Trial

Who Is Running the Clinical Trial?

Oregon Health and Science University

Lead Sponsor

Trials

1,024

Recruited

7,420,000+

John Hunter

Oregon Health and Science University

Chief Medical Officer since 2024

MD, specific details unavailable

Ann Madden Rice

Oregon Health and Science University

Chief Executive Officer

FACHE certification, extensive leadership experience in academic health centers

Findings from Research

In a study of nine shift workers, blood pressure (BP) and heart rate (HR) were monitored over 24 hours, revealing that BP was significantly lower during night shifts compared to day shifts, indicating a disruption in normal circadian rhythms.

The findings suggest that individuals working night shifts experience incomplete adaptation to their work hours, which may necessitate adjustments in hypertension treatment to account for altered BP patterns during sleep and work periods.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Arterial pressure and shift work activities]. Mallion, JM., de Gaudemaris, R., Monzie, A., et al.[2009]

Blunted blood pressure decline during sleep is linked to a higher risk of cardiovascular events, highlighting the importance of managing blood pressure effectively at night.

Taking blood pressure medications like ACE inhibitors and ARBs in the evening rather than the morning can lead to better control of nighttime blood pressure and improve overall cardiovascular health, suggesting that aligning treatment with the body's natural rhythms (chronotherapy) is beneficial.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Circadian rhythms in blood pressure regulation and optimization of hypertension treatment with ACE inhibitor and ARB medications. Hermida, RC., Ayala, DE., Fernández, JR., et al.[2011]

Blood pressure (BP) typically follows a daily pattern, rising during late sleep and peaking in the morning, influenced by various environmental and behavioral factors more than circadian rhythms.

In patients with secondary hypertension, a lack of nighttime BP reduction is observed, and taking long-acting medications at bedtime rather than in the morning leads to better control of hypertension and reduced vascular risk, highlighting the importance of timing in medication administration.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Circadian mechanisms of 24-hour blood pressure regulation and patterning. Smolensky, MH., Hermida, RC., Portaluppi, F.[2018]

Tailoring antihypertensive treatment based on an individual's circadian blood pressure pattern can enhance efficacy and reduce side effects, as shown with medications like nifedipine GITS and valsartan.

Bedtime dosing of certain antihypertensives, such as valsartan, not only improves blood pressure control but also lowers urinary albumin excretion, indicating better kidney protection and overall cardiovascular health.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chronotherapy of hypertension: administration-time-dependent effects of treatment on the circadian pattern of blood pressure. Hermida, RC., Ayala, DE., Calvo, C., et al.[2008]

In a study analyzing 26,170 ambulatory blood pressure monitoring (ABPM) recordings, it was found that 43% of patients, including those with normal blood pressure, exhibited non-dipping patterns, indicating a potential risk for cardiovascular issues.

Age and body mass index (BMI) were significant factors influencing blood pressure patterns, with older patients and those with a BMI over 30 showing higher rates of non-dipping, which could affect their overall cardiovascular health.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ambulatory blood pressure monitoring profiles in a cross-sectional analysis of a large database of normotensive and true or suspected hypertensive patients. Araújo, S., Rouxinol-Dias, A., Mesquita-Bastos, J., et al.[2021]

Using arbitrary times for defining awake and sleep periods in hypertension studies does not significantly change the average blood pressure readings, but it can lead to substantial differences in individual measurements, especially during sleep.

In about 20% to 30% of subjects, the choice of time schedule can alter sleep blood pressure loads by more than 10%, indicating that using actual patient-reported times is crucial for accurate assessment in 24-hour blood pressure monitoring.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of actual versus arbitrary awake and sleep times on analyses of 24-h blood pressure. Peixoto Filho, AJ., Mansoor, GA., White, WB.[2009]

The study analyzed blood pressure (BP) rhythms in 378 subjects, revealing that sleep-time hypertensive individuals have lower 24-hour and 12-hour BP rhythm amplitude and integrity compared to awake-time hypertensives, indicating a disorganized circadian rhythm.

This disorganization in BP rhythms among sleep-time hypertensives may be linked to increased cardiovascular risk, highlighting the importance of monitoring BP patterns during both awake and sleep periods.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Blunting of circadian rhythms and increased acrophase variability in sleep-time hypertensive subjects. Perez-Lloret, S., Risk, M., Golombek, DA., et al.[2008]

References

1. France pubmed.ncbi.nlm.nih.gov

[Arterial pressure and shift work activities]. [2009]

2. United States pubmed.ncbi.nlm.nih.gov

Circadian rhythms in blood pressure regulation and optimization of hypertension treatment with ACE inhibitor and ARB medications. [2011]

3. England pubmed.ncbi.nlm.nih.gov

Circadian mechanisms of 24-hour blood pressure regulation and patterning. [2018]

4. Netherlands pubmed.ncbi.nlm.nih.gov

Sleep irregularity and the association with hypertension and blood pressure levels: the ELSA-Brasil study. [2023]

5. United States pubmed.ncbi.nlm.nih.gov

A review of evidence for the link between sleep duration and hypertension. [2022]

6. Netherlands pubmed.ncbi.nlm.nih.gov

Chronotherapy of hypertension: administration-time-dependent effects of treatment on the circadian pattern of blood pressure. [2008]

7. Spain pubmed.ncbi.nlm.nih.gov

Ambulatory blood pressure monitoring profiles in a cross-sectional analysis of a large database of normotensive and true or suspected hypertensive patients. [2021]

8. United States pubmed.ncbi.nlm.nih.gov

Effects of actual versus arbitrary awake and sleep times on analyses of 24-h blood pressure. [2009]

9. England pubmed.ncbi.nlm.nih.gov

Blunting of circadian rhythms and increased acrophase variability in sleep-time hypertensive subjects. [2008]