Vericiguat for Metabolic Syndrome

Overseen By Gary Gerstenblith, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Johns Hopkins University

Must not be taking: Long-acting nitrates, PDE5 inhibitors

Disqualifiers: Pregnancy, Claustrophobia, Metal implants, others

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 6 weeks

45 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether vericiguat (also known as Verquvo) can improve heart health in people with metabolic syndrome, which includes factors like high blood pressure and high blood sugar. Researchers aim to determine if vericiguat enhances blood flow in the heart. Participants will receive either vericiguat or a placebo (a pill with no active ingredients). The trial seeks individuals with metabolic syndrome and heart blood flow issues, but not severe heart disease. Those with a large waistline, high blood pressure, or high blood sugar, without major heart blockages, may find this trial suitable. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group, offering a chance to contribute to important heart health advancements.

Will I have to stop taking my current medications?

The trial requires that you do not use long-acting nitrates, soluble guanylate cyclase (sGC) stimulators, or phosphodiesterase type 5 (PDE5) inhibitors. If you are taking any of these, you may need to stop before participating.

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

Research shows that vericiguat is generally well-tolerated. In earlier studies, patients taking vericiguat had slightly fewer hospital visits for heart failure compared to those taking a placebo, suggesting it might be safe for most users. Additionally, those on vericiguat experienced fewer heart-related deaths than those on a placebo.

The FDA has approved vericiguat for treating certain heart conditions, indicating its safety for humans. However, like all medications, it may have side effects. So far, data looks promising for its safety in treating metabolic syndrome. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for metabolic syndrome, which often focus on lifestyle changes, blood pressure medications, or glucose-lowering drugs, Vericiguat offers a novel approach. It works by enhancing cyclic guanosine monophosphate (cGMP) production, which can improve heart function and blood vessel relaxation. Researchers are excited about Vericiguat because it targets the underlying vascular dysfunction associated with metabolic syndrome, potentially offering a more direct and effective treatment. Additionally, its oral tablet form makes it easy to administer, which is a plus for patient compliance.

What evidence suggests that vericiguat might be an effective treatment for metabolic syndrome?

Research shows that vericiguat, which participants in this trial may receive, can help treat heart problems, particularly chronic heart failure. Studies have found that people taking vericiguat experienced fewer heart issues compared to those taking a placebo, which contains no active medicine. Specifically, one study found that vericiguat users had fewer heart failure events, and fewer people died from heart-related causes while taking the drug. Although these results focus on heart failure, they suggest that vericiguat might also improve heart health in people with metabolic syndrome by enhancing blood flow in the heart's vessels. ^{1 2 3 4 5}

Who Is on the Research Team?

Thorsten Leucker

Principal Investigator

Johns Hopkins University

Are You a Good Fit for This Trial?

Adults aged 35-85 with metabolic syndrome as defined by NCEP ATP III, which includes having a large waistline, high blood pressure, elevated fasting triglycerides, low HDL cholesterol levels, and raised fasting blood glucose. Participants should not be pregnant or have metal exposure risks due to past occupations like welding. They must also be able to undergo MRI scans without issues such as claustrophobia.

Inclusion Criteria

I meet at least three criteria for metabolic syndrome according to NCEP ATP III.

If you're a man younger than 40 or a woman younger than 50, you should not have any history or symptoms of heart problems. If you're a man older than 40 or a woman older than 50, you should have had a recent test showing no significant blockages in your heart arteries.

I am between 35 and 85 years old.

Exclusion Criteria

I cannot lie flat and still for 45 minutes.

You have metal objects inside your body that cannot be safely scanned with a magnetic resonance (MR) machine.

I have worked in jobs like machining, welding, or metalworking that could expose my eyes to metal.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive vericiguat or placebo with a titration phase: 2.5 mg/day for two weeks, 5 mg/day for two weeks, and 10 mg/day for two weeks

6 weeks

Weekly visits for titration monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Vericiguat

Trial Overview The trial is testing Vericiguat against a placebo in individuals with metabolic syndrome and coronary vascular dysfunction. The study is randomized and double-blind meaning neither the participants nor the researchers know who gets the real treatment versus placebo. The effect on coronary vascular function will be measured using cardiac MRI imaging.

How Is the Trial Designed?

Group I: Vericiguat Experimental Treatment 1 Intervention

Initial 2.5 mg/day for two weeks, then 5 mg/day for two weeks, and then 10 mg/day for two weeks. Systolic blood pressure will be measured before and following each titration The participant will receive the final titration dose for a total of six weeks.. The drug is administered as an oral tablet once daily.

Group II: Placebo Placebo Group 1 Intervention

A placebo tablet will be administered orally once daily.

Vericiguat is already approved in United States, European Union for the following indications:

Approved in United States as Verquvo for:

• Heart failure

Approved in European Union as Verquvo for:

• Chronic heart failure with reduced ejection fraction

Who Is Running the Clinical Trial?

Johns Hopkins University

Lead Sponsor

Trials

2,366

Recruited

15,160,000+

Merck Sharp & Dohme LLC

Industry Sponsor

Trials

4,096

Recruited

5,232,000+

Chirfi Guindo

Merck Sharp & Dohme LLC

Chief Marketing Officer since 2022

Degree in Engineering from Ecole Centrale de Paris, MBA from New York University Stern School of Business

Robert M. Davis

Merck Sharp & Dohme LLC

Chief Executive Officer since 2021

JD from Northwestern University Pritzker School of Law, MBA from Northwestern University Kellogg Graduate School of Management, Bachelor's in Finance from Miami University

Published Research Related to This Trial

The metabolic syndrome, characterized by obesity, high blood pressure, insulin resistance, and dyslipidemia, is a significant risk factor for coronary heart disease and type 2 diabetes, necessitating prompt management of its components.

New investigational drugs targeting cannabinoid type 1 receptors show promise in treating metabolic syndrome, highlighting the need for further research into effective therapies for this condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A constellation of complications: the metabolic syndrome. Grundy, SM.[2022]

The metabolic syndrome is a serious health condition characterized by a combination of factors like high blood sugar, high blood pressure, unhealthy cholesterol levels, and abdominal obesity, which significantly increase the risk of type 2 diabetes and cardiovascular diseases.

It affects 10 to 30% of adults in industrialized countries, with a rising trend, especially among women, highlighting the importance of identifying individuals with metabolic syndrome beyond just those who are overweight or obese.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[How to manage the metabolic syndrome?]. Andreelli, F., Ziegler, O.[2017]

Metabolic syndrome (MS) is a significant public health issue that increases the risk of serious conditions like heart disease and type 2 diabetes, making early identification of at-risk populations crucial for effective management.

The primary treatment for metabolic syndrome involves lifestyle changes such as diet and exercise, but pharmacological therapies targeting obesity, insulin resistance, dyslipidemia, and hypertension are also essential for high-risk individuals.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Metabolic syndrome. Part III: its prevention and therapeutic management]. Pacholczyk, M., Ferenc, T., Kowalski, J.[2017]

Metabolic syndrome is a significant health condition characterized by a combination of risk factors such as insulin resistance, abdominal obesity, dyslipidemia, and hypertension, which increase the risk of cardiovascular and metabolic diseases.

Effective management of metabolic syndrome requires both lifestyle changes and long-term pharmacologic treatment, highlighting the complexity of its drug therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Background and treatment of metabolic syndrome: a therapeutic challenge. van Zwieten, PA., Mancia, G.[2017]

Metabolic syndrome affects about 34% of adults in the USA and is linked to serious health risks, including cardiovascular diseases, with diagnosis based on three of five specific health conditions.

Chronic stress may contribute to the development of metabolic syndrome by disrupting the HPA axis, highlighting the importance of lifestyle changes and potential drug therapies for effective management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Metabolic syndrome a widespread threatening condition; risk factors, diagnostic criteria, therapeutic options, prevention and controversies: an overview. Amihăesei, IC., Chelaru, L.[2022]

Citations

1. ncbi.nlm.nih.gov ncbi.nlm.nih.gov/books/NBK596771/

Clinical Review - Vericiguat (Verquvo) - NCBI - NIH Efficacy Results. A summary of the results for the main efficacy and safety outcomes of the VICTORIA trial is presented in Table 2. Time to First Event of CV ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT05711719?term=metabolic%20syndrome&aggFilters=studyType:int,phase:1%202%203,ages:adult,funderType:industry&viewType=Table&rank=7

Vericiguat in Patients With Metabolic Syndrome and ... The investigators will conduct a randomized, double-blind placebo-controlled study in individuals with the metabolic syndrome and baseline coronary vascular ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11796121/

Efficacy of vericiguat in patients with chronic heart failure and ... At six months, the Vericiguat group exhibited a significant reduction in patients classified as C (from 31.6 to 7.5%) and D (from 31.6 to 3.7%), ...

4. merck.com merck.com/news/merck-provides-new-results-for-verquvo-vericiguat-in-patients-with-chronic-heart-failure-and-reduced-ejection-fraction/

Merck Provides New Results for VERQUVO® (vericiguat) ... For the key secondary endpoints, cardiovascular death was numerically lower with VERQUVO (9.6%) compared to placebo (11.3%) (HR 0.83; 95% CI ...

5. acc.org acc.org/latest-in-cardiology/articles/2025/08/26/11/47/sat-243am-vericiguat-esc-2025

VICTOR AND VICTORIA: Late-Breaking Science Explore ... Results showed primary outcome events occurred in 549 (18%) of patients assigned to vericiguat compared with 584 (19%) assigned to placebo over ...