Neuropeptide Y for High Blood Pressure

(OB-HTN Trial)

Overseen By Mary Childers

Age: 18 - 65

Sex: Any

Trial Phase: Phase < 1

Sponsor: University of Texas Southwestern Medical Center

Disqualifiers: Cardiovascular disease, Renal disease, Smoking, Diabetes

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

Compensation: Varies

Number of Visits: 1

Duration: 1 day

100 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how the nervous system affects blood pressure, particularly under stress. Researchers study the impact of conditions like high blood pressure (hypertension) and obesity on this process. The trial uses Neuropeptide Y, a molecule that influences blood vessels, to examine its effects on blood pressure. Suitable participants include those with high blood pressure but not obese, those who are obese but not hypertensive, obese individuals with high blood pressure, and healthy individuals with normal weight and no history of cardiovascular disease. As an Early Phase 1 trial, this research aims to understand how Neuropeptide Y functions in people, offering participants a unique opportunity to contribute to groundbreaking scientific discovery.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

Is there any evidence suggesting that Neuropeptide Y is likely to be safe for humans?

Research has shown that Neuropeptide Y (NPY) helps control blood pressure and heart functions. However, its safety for humans remains uncertain. Some studies suggest that NPY is not crucial for maintaining normal blood pressure in certain animals. In contrast, other studies indicate that prolonged use of NPY might raise blood pressure and cause heart changes. More research is needed to determine the safety of NPY for people, especially those with high blood pressure or obesity. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Neuropeptide Y is unique because it offers a novel approach to treating high blood pressure by targeting the nervous system, unlike typical medications that often focus on the cardiovascular system. Most current treatments, like ACE inhibitors and beta-blockers, operate by relaxing blood vessels or reducing heart rate. Neuropeptide Y, however, works by modulating the sympathetic nervous system, which can potentially offer more precise control over blood pressure with fewer side effects. This innovative mechanism is what excites researchers, as it could provide a more effective and tailored treatment for patients with high blood pressure, especially those who are not well-served by existing therapies.

What evidence suggests that Neuropeptide Y might be an effective treatment for high blood pressure?

Research has shown that Neuropeptide Y (NPY) can affect blood pressure by narrowing blood vessels, which might help manage high blood pressure. Narrower blood vessels can lead to higher blood pressure. One study found that NPY might also work in the brain to help lower blood pressure. Thus, NPY could control blood pressure in two ways: by narrowing blood vessels and by acting in the brain. However, these findings are still in the early stages, and more research is needed to fully understand how NPY affects high blood pressure. Participants in this trial will be divided into groups: hypertensive, obese, obese-hypertensive, and healthy control, to study the effects of NPY across these conditions. ^{3 4 6 7 8}

Are You a Good Fit for This Trial?

This trial is for adults aged 18-55 who are either healthy, overweight (BMI>30), have high blood pressure, or both. Participants must not have other significant cardiovascular diseases, kidney disease, a history of smoking, or diabetes.

Inclusion Criteria

If you are between the ages of 18 and 55 and have high blood pressure, you may not be eligible if you are not obese, or if your body mass index (BMI) is less than 30.

I am between 18-55, have a BMI over 30, and diagnosed with high blood pressure.

I am 18-55 years old, have a BMI under 30, and my high blood pressure was confirmed by a 24-hour monitor.

Exclusion Criteria

People with diabetes are not allowed in the study.

I have a significant heart condition.

I have kidney disease.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants undergo physiological stress protocols and drug infusions to measure sympathetic nervous system activity and blood flow

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Neuropeptide Y

Trial Overview

The study aims to understand how stress affects blood pressure in people with obesity and/or hypertension by measuring nervous system activity and blood flow during stress tests and drug-induced changes in vessel size.

How Is the Trial Designed?

Group I: Obese-hypertensive Experimental Treatment 1 Intervention

Obese adults who are being treated for hypertension

Group II: Obese Experimental Treatment 1 Intervention

Obese adults who are not hypertensive

Group III: Hypertensive Experimental Treatment 1 Intervention

Hypertensive adults who are not obese

Group IV: Healthy Control Experimental Treatment 1 Intervention

Healthy age matched controls with no history of cardiovascular disease and normal bodyweight

Who Is Running the Clinical Trial?

University of Texas Southwestern Medical Center

Lead Sponsor

Trials

1,102

Recruited

1,077,000+

Published Research Related to This Trial

In a study of 189 patients with end-stage renal disease (ESRD), those carrying the C allele of the NPY receptor Y2 gene had a significantly higher left ventricular mass index (LVMI), indicating a potential genetic risk factor for heart complications.

The research found that higher plasma levels of neuropeptide Y (NPY) were linked to increased LVMI specifically in patients with the C allele, suggesting that this genetic variation may enhance the impact of NPY on heart remodeling in ESRD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neuropeptide Y receptor Y2 gene polymorphism interacts with plasma neuropeptide Y levels in predicting left ventricular hypertrophy in dialysis patients. Testa, A., Mallamaci, F., Macrì, R., et al.[2010]

Genetically hypertensive rats (SHR) have higher levels of neuropeptide Y (NPY) in their platelets compared to normotensive rats (WKY), suggesting a genetic link to hypertension.

The study found that while NPY is released from platelets during aggregation with collagen, this release is significantly greater in hypertensive rats, indicating that NPY may play a role in vascular complications associated with hypertension.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Platelet neuropeptide Y in spontaneously hypertensive rats. Ogawa, T., Kitamura, K., Kangawa, K., et al.[2006]

Neuropeptide Y (NPY) has direct vasoconstrictor properties that can affect blood pressure independently of adrenergic activation, indicating its potential role in cardiovascular regulation.

NPY may enhance the effects of other substances that stimulate blood vessels and could influence blood pressure by regulating hormone release related to cardiovascular function.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cardiovascular effects of neuropeptide Y. Waeber, B., Aubert, JF., Corder, R., et al.[2019]

Neuropeptide Y (NPY) plays a significant role in regulating blood pressure by causing blood vessels to constrict and enhancing the effects of noradrenaline, while also inhibiting noradrenaline release, indicating its potential as a target for hypertension treatment.

The discovery of multiple NPY receptors (Y1, Y2, and Y3) and their varying responses to NPY and related peptides suggests that developing specific receptor antagonists could lead to new therapeutic strategies for managing conditions like primary hypertension.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Multiple neuropeptide Y receptors are involved in cardiovascular regulation. Peripheral and central mechanisms. Grundemar, L., Håkanson, R.[2019]

Neuropeptide Y (NPY) is involved in regulating cardiovascular function and blood pressure, acting as a cotransmitter in sympathetic neurons and influencing responses in both the brain and peripheral tissues.

In hypertension, the effects of NPY may change, leading to increased vasoconstriction and potential contributions to the development of high blood pressure, suggesting it could be a target for future research and treatment strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neuropeptide Y: a possible role in hypertension? Michel, MC., Rascher, W.[2006]

In spontaneously hypertensive rats (SHR), there are higher levels of neuropeptide Y (NPY) in platelet-rich plasma compared to age-matched Wistar-Kyoto (WKY) rats, indicating a potential role of NPY in the development of hypertension.

As SHR age, their responsiveness to vasopressor agents like norepinephrine and NPY increases, suggesting that the mechanisms of hypertension may involve enhanced sympathetic activity and NPY release, particularly in younger SHR.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Modulation of vascular function by neuropeptide Y during development of hypertension in spontaneously hypertensive rats. Zukowska-Grojec, Z., Golczynska, M., Shen, GH., et al.[2019]

Neuropeptide Y (NPY) is a key peptide involved in regulating blood pressure by modulating the sympathetic nervous system, highlighting its potential role in cardiovascular health.

The review discusses how NPY influences vascular tone and cardiac function through various mechanisms, suggesting its importance in understanding blood pressure control and potential therapeutic targets.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The role of neuropeptide Y in cardiovascular regulation. Walker, P., Grouzmann, E., Burnier, M., et al.[2019]

Patients with pregnancy-induced hypertension (PIH) had significantly higher plasma neuropeptide Y (NPY) levels compared to normal non-pregnant and normal pregnant women, indicating a potential link between elevated NPY and PIH.

After delivery, plasma NPY levels decreased in moderate and severe PIH patients, but levels remained elevated compared to normal non-pregnant women, suggesting that NPY may contribute to the persistence of hypertension even after pregnancy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Changes of plasma level of neuropeptide Y in patients with pregnancy induced hypertension]. Jin, L., Wang, C.[2006]

Neuropeptide Y (NPY) plays a significant role in regulating cardiovascular functions, and abnormalities in its release or receptor activity may lead to serious conditions like hypertension and heart failure.

The identification of different NPY receptor subtypes opens up the possibility for creating targeted treatments that could specifically address cardiovascular diseases by modulating these receptors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The therapeutic potential of neuropeptide Y in cardiovascular disease. Hudspith, MJ., Munglani, R.[2019]

Citations

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pubmed.ncbi.nlm.nih.gov

pubmed.ncbi.nlm.nih.gov/7629398/

Neuropeptide Y: a possible role in hypertension?

Purpose: To evaluate whether neuropeptide Y (NPY) is likely to be relevant as a regulator of cardiovascular function in general and of blood pressure ...

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frontiersin.org

frontiersin.org/journals/physiology/articles/10.3389/fphys.2018.01281/full

The Role of Neuropeptide Y in Cardiovascular Health and ...

Zhang et al. have demonstrated that long-term subcutaneous administration of NPY results in increased systolic blood pressure and hypertension-induced ...

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ahajournals.org

ahajournals.org/doi/10.1161/01.hyp.0000153953.69799.f2

Central Neuropeptide Y Signaling Ameliorates N(ω)

This study tested the hypothesis that neuropeptide Y functions as a central neurotransmitter to lower blood pressure, therefore its increased ...

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withpower.com

withpower.com/trial/neuropeptide-y-for-high-blood-pressure-0350b

Neuropeptide Y for High Blood Pressure (OB-HTN Trial)

Research suggests that Neuropeptide Y (NPY) can directly cause blood vessels to constrict, which might help control blood pressure. It also enhances the effects ...

5.

sciencedirect.com

sciencedirect.com/science/article/abs/pii/0167011590900596

Effects of neuropeptide Y and noradrenaline on uterine ...

NA (10–1000 pmol) had similar effects, increasing local blood pressure (5%–57.5% (P < 0.01)). NPY had no significant effect on uterine blood flow velocity as ...

6.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC2739783/

Neuropeptide Y and neurovascular control in skeletal ...

Evidence from Y1R knockout mice that display normal basal blood pressure (85) suggests that NPY does not play a critical role in blood pressure maintenance.

7.

ahajournals.org

ahajournals.org/doi/10.1161/hypertensionaha.112.197855

Neuropeptide Y Promoter Polymorphism Modifies Effects of ...

Neuropeptide Y (NPY) is implicated in the regulation of blood pressure (BP), and NPY pathways in the hypothalamus are sensitive to dietary ...

8.

sciencedirect.com

sciencedirect.com/science/article/pii/S1525001621004998

Neuropeptide Y attenuates cardiac remodeling and ...

We found that AMI mice lacking NPY developed more severe AMI than WT mice with worse cardiac dysfunction, progressive cardiac inflammation and fibrosis.