Forced Desynchrony for High Blood Pressure

Overseen By Nicole P Bowles, PhD

Age: 18 - 65

Sex: Any

Trial Phase: Academic

Sponsor: Oregon Health and Science University

Must not be taking: Antihypertensives, Caffeine, Nicotine, Alcohol

Disqualifiers: Severe renal disease, Sleep apnea, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 9

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to understand how sleep patterns, body clock rhythms, and behaviors affect blood pressure in Black adults with hypertension. Researchers are exploring whether targeting these factors can improve hypertension treatments and if optimal treatment options might vary by race. Participants will follow a "forced desynchrony" protocol, adjusting their sleep and activity schedules to study these effects. The trial seeks Black or White participants with mild to moderate high blood pressure who are not on medication and can avoid caffeine, nicotine, alcohol, and certain other substances. As an unphased trial, it offers participants the opportunity to contribute to groundbreaking research that could lead to more personalized hypertension treatments.

Will I have to stop taking my current medications?

Yes, you must be free of all prescription and non-prescription drugs, including caffeine, nicotine, alcohol, and herbal medications, to participate in this trial.

What prior data suggests that this protocol is safe for high blood pressure?

Research has shown that forced desynchrony, a method used to study how body clocks affect blood pressure, has been examined in past studies. These studies reveal that altering the body's natural sleep-wake cycle can demonstrate how blood pressure varies throughout the day. While these studies aim to understand blood pressure patterns, information on the safety or side effects of this method remains limited.

As this trial is in its early stages, complete safety information might not yet be available. Prospective participants should consult with the medical team to learn about any possible risks or side effects. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about the Forced Desynchrony protocol for high blood pressure because it offers a novel approach compared to traditional treatments like lifestyle changes, diuretics, and ACE inhibitors. Unlike these standard methods, which focus on managing blood pressure through medication or lifestyle modification, Forced Desynchrony examines the impact of altering the body's natural circadian rhythms. By intentionally desynchronizing sleep and wake cycles, researchers hope to uncover new insights into how these rhythms affect blood pressure regulation. This could pave the way for innovative strategies to manage high blood pressure by targeting the body's internal clock, rather than just the cardiovascular system directly.

What evidence suggests that this forced desynchrony protocol is effective for high blood pressure?

Research has shown that altering the usual sleep-wake cycle, known as forced desynchrony, reveals how blood pressure links to the body's internal clock. In this trial, all participants will undergo a forced desynchrony protocol. Studies have found that blood pressure naturally rises in the late afternoon. This approach helps researchers observe how changes in the body's internal clock impact blood pressure. Understanding these patterns could be crucial for discovering new methods to manage high blood pressure, especially in Black adults who might experience different effects from these internal rhythms. Early results suggest that focusing on these rhythms could improve blood pressure control. ^{1 2 3 4 6}

Who Is on the Research Team?

Steven A Shea, PhD

Principal Investigator

Ore

Are You a Good Fit for This Trial?

This trial is for self-identified Black or White adults who are either 'normotensive' with blood pressure under 140/90 mmHg, or have stage 1 hypertension with systolic BP between 140 and 160 mmHg or diastolic BP between 90 and 100 mmHg. Participants should not be on any medication (including caffeine and alcohol), must not smoke, do night shifts, or have traveled across time zones recently. They also shouldn't have severe health issues like renal disease.

Inclusion Criteria

Self-identified Black or White

I am not taking any prescription, over-the-counter drugs, or substances like caffeine or alcohol.

Your blood pressure should be normal or slightly high, but not too high.

Exclusion Criteria

You have smoked in the past year.

I have been diagnosed with moderate to severe sleep apnea.

I have no severe health issues except possibly mild high blood pressure or serious kidney disease.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Forced Desynchrony Protocol

Participants undergo a forced desynchrony protocol to study sleep, circadian, and behavioral mechanisms affecting blood pressure

7 days

7-day lab stay

Ambulatory Monitoring

Participants undergo 24-hour ambulatory blood pressure monitoring to estimate blood pressure dipping status

2 days

2-day ambulatory period

Follow-up

Participants are monitored for safety and effectiveness after the main protocol

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Forced Desynchrony

Trial Overview The study investigates how sleep, circadian rhythms, and behaviors contribute to non-dipping blood pressure profiles in Black adults compared to White adults. It aims to understand if race influences the best treatment for hypertension by examining these different factors.

How Is the Trial Designed?

Group I: Forced Desynchrony Experimental Treatment 1 Intervention

All participants will undergo a forced desynchrony protocol.

Who Is Running the Clinical Trial?

Oregon Health and Science University

Lead Sponsor

Trials

1,024

Recruited

7,420,000+

Published Research Related to This Trial

Patients with heart failure and left ventricular dyssynchrony show significantly altered hemodynamic forces compared to healthy individuals, indicating a potential new way to assess cardiac function using 4-D flow MRI.

The study found that diastolic force patterns can effectively distinguish between healthy and diseased hearts, suggesting that analyzing these forces could improve risk stratification and guide cardiac resynchronization therapy (CRT) decisions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hemodynamic forces using four-dimensional flow MRI: an independent biomarker of cardiac function in heart failure with left ventricular dyssynchrony? Arvidsson, PM., Töger, J., Pedrizzetti, G., et al.[2020]

Cardiac resynchronization therapy, particularly biventricular pacing, is highly effective for patients with congestive heart failure and severe left ventricular dysfunction, improving heart function by coordinating contractions without increasing heart muscle strength.

Atrial resynchronization may help prevent atrial fibrillation in certain patients, but its overall antiarrhythmic benefits are less clear compared to the well-established advantages of ventricular resynchronization.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

What is cardiac resynchronization therapy? Barold, SS.[2019]

In a study of 3253 patients with CRT-D devices followed for a median of 18 months, device-related events were more common than in single- or dual-chamber defibrillators, with 50% of patients requiring surgical revision for battery depletion within four years.

Despite the higher frequency of complications, such as infections and lead dislodgements, these device-related events did not lead to worse clinical outcomes, as the risk of death was similar between patients with and without surgical revisions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term complications related to biventricular defibrillator implantation: rate of surgical revisions and impact on survival: insights from the Italian Clinical Service Database. Landolina, M., Gasparini, M., Lunati, M., et al.[2022]

In a study of 51 chronically right ventricular-paced patients with severe heart failure, 15 patients (29%) showed significant improvement in left ventricular function after upgrading to cardiac resynchronization therapy (CRT-D), indicating that CRT can effectively reverse heart failure symptoms in certain patients.

Key predictors of positive response to CRT included smaller left ventricular dimensions and a shorter duration of cardiomyopathy, with hyperresponders experiencing excellent long-term survival, as none required transplants or mechanical support during a follow-up period of about 42 months.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Predicting hyperresponse among pacemaker-dependent nonischemic cardiomyopathy patients upgraded to cardiac resynchronization. Adelstein, E., Schwartzman, D., Gorcsan, J., et al.[2022]

Cardiac resynchronization therapy (CRT) has emerged as a highly effective treatment for improving cardiac efficiency in patients with heart failure by addressing cardiac dyssynchrony, a condition that has been recognized for over 50 years.

Recent advancements in CRT technology and large-scale clinical trials have led to its widespread adoption, highlighting the importance of proper patient selection and ongoing monitoring for optimal outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cardiac resynchronization therapy: redefining the role of device therapy in heart failure. Viswanathan, K., Ghosh, J., Kaye, GC., et al.[2010]

In a study of 30 heart failure patients, it was found that any form of ventricular pacing can enhance heart contractile function if it reduces baseline biventricular mechanical asynchrony, measured by the NPP loop area.

Biventricular pacing was particularly effective, showing a 16% greater increase in contractile function compared to right ventricular pacing, but improvements depend on the level of baseline asynchrony, indicating that biventricular resynchronization is just one of several mechanisms that can lead to better heart function.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Biventricular mechanical asynchrony predicts hemodynamic effect of uni- and biventricular pacing. Yu, Y., Kramer, A., Spinelli, J., et al.[2020]

Biventricular pacing significantly improves functional capacity in patients with severe heart failure, as evidenced by a reduction in NYHA functional class from IV to II after one year.

The therapy also enhances left ventricular function, demonstrated by increased ejection fraction and reduced mitral regurgitation, with sustained improvements in exercise capacity over the long term.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Biventricular pacing in end-stage heart failure improves functional capacity and left ventricular function. Bakker, PF., Meijburg, HW., de Vries, JW., et al.[2019]

Cardiac re-synchronization therapy is increasingly recognized as an effective treatment for heart failure patients experiencing de-synchronized heart contractions, particularly due to left bundle branch block.

The study emphasizes the use of conventional echocardiography to assess different types of dyssynchrony (atrioventricular, interventricular, and intraventricular), allowing for a better understanding of the mechanical issues in the heart without relying on advanced imaging techniques.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Is standard-echocardiography sufficient for identification of responders?]. Neuss, M., Flach, P., Ali, T., et al.[2018]

A novel heart failure model using rapid pacing combined with forced ventricular desynchronization in 20 pigs resulted in more severe hemodynamic impairment compared to traditional models, indicating its effectiveness for studying heart failure.

Group B, which experienced desynchronized pacing, showed significantly worse cardiac function and increased heart-to-body weight ratio, along with greater histological changes like cell enlargement and fibrosis, highlighting the model's ability to mimic advanced heart failure conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Desynchronization: a novel model to induce heart failure. Möllmann, H., Voss, S., Nef, HM., et al.[2009]

Cardiac resynchronization therapy (CRT) is an effective treatment for patients with heart failure and left ventricular dysynchrony, supported by evidence from over 4000 randomized controlled trials and additional observational studies.

CRT significantly improves heart function, exercise tolerance, quality of life, and reduces hospitalization and mortality rates in patients classified as New York Heart Association class III and IV.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cardiac resynchronization therapy. Abraham, WT.[2007]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10947115/

Hypertension: Causes and Consequences of Circadian ... A Forced Desynchrony protocol with an imposed 10 hr and 40 min sleep/wake cycle also showed an endogenous circadian rhythm in BP with a peak around 4-6 pm. A ...

2. ahajournals.org ahajournals.org/doi/10.1161/CIRCRESAHA.124.323515

Hypertension: Causes and Consequences of Circadian ... Here, we review the impact of daily rhythms and circadian systems in regulating blood pressure and the onset, progression, and consequences of hypertension.

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11446228/

Circadian Disruption and the Molecular Clock in ... Disruption of circadian rhythms is associated with negative health outcomes including cardiovascular disease and hypertension. Importantly, ...

4. journals.lww.com journals.lww.com/jhypertension/fulltext/2025/08000/nocturnal_blood_pressure__pathophysiology,.4.aspx

Nocturnal blood pressure: pathophysiology, measurement ... Under unmasking conditions of forced desynchrony, the circadian rhythm of BP reveals a peak in the late subjective day. However, the peak-to-trough amplitude of ...

5. academic.oup.com academic.oup.com/sleep/advance-article/doi/10.1093/sleep/zsaf295/8262813

Circadian mechanisms underlying post-exercise blood ... To test this hypothesis, we conducted a 30-hour circadian “forced desynchrony” (FD) protocol in healthy adults, incorporating five identical ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT05184933

Sleep and Circadian Mechanisms in Hypertension 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 ...