What is the mechanism of action of this treatment?

Common treatments for high blood pressure include ACE inhibitors, beta blockers, diuretics, and calcium channel blockers. ACE inhibitors reduce the production of angiotensin II, a hormone that narrows blood vessels, thereby lowering blood pressure. Beta blockers decrease heart rate and the force of contraction, reducing blood pressure. Diuretics help the kidneys remove excess sodium and water, decreasing blood volume and pressure. Calcium channel blockers prevent calcium from entering heart and blood vessel cells, leading to relaxed vessels and lower pressure. In the context of ETB receptor modulation, understanding these mechanisms is crucial as ETB receptor dysfunction in obesity-related hypertension may require targeted therapies that address specific pathways involved in blood vessel constriction and fluid balance.

What side effects are associated with this type of intervention?

Common treatments for high blood pressure, particularly those involving endothelin receptor antagonists, include non-selective endothelin receptor antagonists like bosentan. Known side effects of these treatments can include fluid retention, which may lead to worsening heart failure and necessitate hospitalization. Other adverse effects may include dizziness, headache, and potential liver enzyme abnormalities. It is important to monitor patients closely for these side effects to manage them effectively.

What prior FDA approvals exist?

The FDA has approved several classes of drugs for the treatment of high blood pressure, including angiotensin-converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARBs), calcium channel blockers, and diuretics. Specifically related to the endothelin system, endothelin receptor antagonists like bosentan and macitentan have been studied, although they have shown limited clinical benefit and concerns about fluid retention. These treatments are part of ongoing research to understand their efficacy in conditions like obesity-related hypertension, where ETB receptor dysfunction may play a significant role.

What other types of research exist?

Promising alternatives to ETB receptor modulation for treating high blood pressure in 2024 include: <ol> <li>ARNI (Angiotensin Receptor-Neprilysin Inhibitors): Sacubitril-valsartan has shown consistent benefits in reducing mortality and hospitalization in heart failure patients, which may extend to hypertensive patients.</li> <li>SGLT2 Inhibitors: These drugs, primarily used for diabetes, have shown significant cardiovascular benefits, including blood pressure reduction.</li> <li>Mineralocorticoid Receptor Antagonists (MRAs): Eplerenone and spironolactone have demonstrated efficacy in reducing blood pressure and improving heart failure outcomes.</li> <li>Selective Endothelin Receptor Antagonists: While non-selective antagonists like bosentan have had mixed results, selective antagonists may offer targeted benefits with fewer side effects.</li> <li>Lifestyle Interventions: Continued emphasis on weight management, dietary changes (e.g., DASH diet), and physical activity remains crucial for managing hypertension, particularly in obese patients.</li> </ol>

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Angiotensin II Receptor Blocker

Candesartan for High Blood Pressure in Obesity (END-RF Trial)

Phase < 1

Waitlist Available

Led By Ryan Harris, PHD, CES

Research Sponsored by Augusta University

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Adult between the ages of 18-40 years old

Be between 18 and 65 years old

Must not have

Uncontrolled hypertension (treated resting SBP >140 mm Hg or DBP >90 mm Hg)

Using medications that affect vascular tone (i.e., nitrates, etc.)

Timeline

Screening 3 weeks

Treatment Varies

Follow Up pre-treatment baseline and 7 days post-treatment

Summary

This trial will use chemicals and a drug called Candesartan to study how they affect certain receptors related to blood pressure. It focuses on obese individuals who often have high levels of a substance called ET-1, which is linked to high blood pressure. By blocking these receptors, the study aims to see if it can improve their function and help lower blood pressure in obese people. Candesartan has been studied extensively for its effects on blood pressure, particularly in hypertensive and obese patients.

Who is the study for?

This trial is for adults aged 18-40 who are dealing with high blood pressure and obesity. It's not open to those with cardiovascular, lung, kidney, liver, brain diseases or metabolic disorders; pregnant individuals; people on meds that affect blood vessels or anticoagulants like aspirin; those with anemia, postmenopausal women, or uncontrolled hypertension.

What is being tested?

The study is testing the effects of Candesartan (a drug) against a placebo to see if it can improve how well ETB receptors work in obese individuals. This could help understand if these receptors play a role in developing high blood pressure due to obesity.

What are the potential side effects?

Candesartan may cause dizziness, increased potassium levels which can affect heart rhythm, low blood pressure especially after standing up quickly, and possible kidney problems. Placebos typically have no active ingredients but can lead to perceived side effects.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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I am between 18 and 40 years old.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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My blood pressure is not controlled, even with treatment.

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I am taking medication that affects blood vessel function.

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I am currently taking blood thinners.

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I have gone through menopause.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ pre-treatment baseline and 7 days post-treatment

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~pre-treatment baseline and 7 days post-treatment

This trial's timeline: 3 weeks for screening, Varies for treatment, and pre-treatment baseline and 7 days post-treatment for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Percentage Change in Flow-Mediated Dilation (FMD)

Side effects data

From 2008 Phase 4 trial • 315 Patients • NCT00348686

Headache

Dizziness

100%

80%

60%

40%

20%

Study treatment Arm

Candesartan

Trial Design

2Treatment groups

Experimental Treatment

Placebo Group

Group I: CandesartanExperimental Treatment1 Intervention

Sub chronic (7 days) Candesartan (16 mg/day)

Group II: PlaceboPlacebo Group1 Intervention

Endothelial function will be determined following a seven day treatment of placebo

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Candesartan

2005

Completed Phase 4

~11970

0 / 5Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Common treatments for high blood pressure include ACE inhibitors, beta blockers, diuretics, and calcium channel blockers. ACE inhibitors reduce the production of angiotensin II, a hormone that narrows blood vessels, thereby lowering blood pressure. Beta blockers decrease heart rate and the force of contraction, reducing blood pressure. Diuretics help the kidneys remove excess sodium and water, decreasing blood volume and pressure. Calcium channel blockers prevent calcium from entering heart and blood vessel cells, leading to relaxed vessels and lower pressure. In the context of ETB receptor modulation, understanding these mechanisms is crucial as ETB receptor dysfunction in obesity-related hypertension may require targeted therapies that address specific pathways involved in blood vessel constriction and fluid balance.

The endothelin system as target for therapeutic interventions in cardiovascular and renal disease.Endothelin receptor antagonists in heart failure: current status and future directions.Novel neuropeptides in the pathophysiology of heart failure: adrenomedullin and endothelin-1.