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

Trial Summary

What is the purpose of this trial?

This trial is testing vericiguat, a drug that helps blood vessels relax and widen, in people with metabolic syndrome and poor heart blood flow. The goal is to see if it can improve heart function. The study will use MRI scans and other tests to measure changes in heart health. Vericiguat is currently being tested for chronic heart failure.

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.

How does the drug Vericiguat differ from other treatments for metabolic syndrome?

Vericiguat is unique because it works by stimulating an enzyme called soluble guanylate cyclase, which helps relax blood vessels and improve blood flow, potentially addressing multiple components of metabolic syndrome like high blood pressure and heart health, unlike traditional treatments that often target individual symptoms separately. ^{1 2 3 4 5}

Research Team

Thorsten Leucker

Principal Investigator

Johns Hopkins University

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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]

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]

References

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

[How to manage the metabolic syndrome?]. [2017]

2. Poland pubmed.ncbi.nlm.nih.gov

[Metabolic syndrome. Part III: its prevention and therapeutic management]. [2017]

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

Background and treatment of metabolic syndrome: a therapeutic challenge. [2017]

4. Romania pubmed.ncbi.nlm.nih.gov

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

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

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