Vericiguat for Insulin Resistance

(VITAL-IMPACT Trial)

Overseen By Naman Shetty, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: University of Alabama at Birmingham

Must not be taking: Antidiabetics, Antihypertensives

Disqualifiers: Cardiovascular diseases, Diabetes, 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: 12 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether vericiguat (Verquvo) can improve heart and metabolic health in Black individuals with insulin resistance who are also obese. The researchers aim to determine if it can enhance insulin sensitivity (how well the body uses insulin) and energy use. Participants will take either vericiguat or a placebo (a pill with no active medicine) for 12 weeks. This trial suits Black adults with a BMI of 30 or more who struggle with insulin resistance but do not have diabetes or significant heart issues. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

If you are taking up to two classes of blood pressure medications, you may need to stop them for one week before joining the trial. The protocol does not specify other medication restrictions.

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

Research has shown that vericiguat is generally well-tolerated. In earlier studies, patients taking vericiguat had a lower risk of heart problems compared to those taking a placebo, a pill with no active medicine. This suggests that vericiguat is relatively safe, particularly for heart health.

Vericiguat has already received approval for treating certain heart conditions, indicating it has passed thorough safety tests. Animal studies did not find any special risks, which often suggests similar results in humans. While side effects can occur with any medication, the evidence so far indicates that vericiguat is safe for further study in people. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for insulin resistance?

Vericiguat is unique because it offers a new approach to tackling insulin resistance by targeting the sGC (soluble guanylate cyclase) pathway. Most treatments for insulin resistance, like metformin or lifestyle changes, focus on improving insulin sensitivity or reducing glucose production. However, Vericiguat enhances the production of cyclic GMP, which can improve blood flow and reduce oxidative stress in cells, potentially addressing the underlying causes of insulin resistance in a novel way. Researchers are excited about Vericiguat because it brings a fresh mechanism of action to the table, which might offer benefits where traditional therapies fall short.

What evidence suggests that vericiguat might be an effective treatment for insulin resistance?

Research has shown that vericiguat, a drug that activates a specific enzyme, may improve heart health. In previous studies, vericiguat lowered the risk of heart problems and reduced hospital visits for people with heart failure. The drug increases levels of a molecule called cGMP, which plays a role in many important body functions. This trial will test vericiguat's potential to improve insulin resistance. Early findings suggest that boosting cGMP activity might also enhance how the body uses insulin and energy, especially in people with insulin resistance. ^{1 2 3 4 6}

Who Is on the Research Team?

Pankaj Arora, MD

Principal Investigator

University of Alabama at Birmingham

Are You a Good Fit for This Trial?

This trial is for Black individuals who are obese and have insulin resistance. Participants will undergo various tests, including MRI-PET scans, tissue biopsies, and energy expenditure assessments. People with allergies or other metabolic diseases may not be eligible.

Inclusion Criteria

Willing to adhere to study protocol

BMI ≥ 30 kg/m2

Self-identified race/ethnicity as African-American or Black

Exclusion Criteria

My blood pressure is over 160/100 mmHg or I take three or more blood pressure medications.

I have diabetes or my blood sugar/HbA1C levels are high.

I am not pregnant, breastfeeding, and I use effective birth control or practice abstinence.

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 in a double-blind manner to assess improvements in insulin sensitivity and energy expenditure

12 weeks

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 study is testing vericiguat, a drug that targets the cGMP pathway believed to improve heart health and metabolism in obese Black individuals with insulin resistance. It's compared against a placebo over 12 weeks to see if it affects body fat, energy use, and insulin sensitivity.

How Is the Trial Designed?

Group I: Experimental: Vericiguat Experimental Treatment 5 Interventions

The subject will be randomized, in a double-blind manner to vericiguat 10 mg once daily for a period of 12 weeks.

Group II: Placebo Placebo Group 5 Interventions

The subject will be randomized, in a double-blind manner to placebo once daily for a period of 12 weeks.

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?

University of Alabama at Birmingham

Lead Sponsor

Trials

1,677

Recruited

2,458,000+

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06320951

VITAL-IMPACT: Improving Cardiometabolic Health in Black ... This study investigates the potential of vericiguat, a soluble guanylate cyclase stimulator, to improve cardiometabolic health in obese Black individuals ...

2. sciencedirect.com sciencedirect.com/science/article/pii/S2213177924004190

Vericiguat and Cardiovascular Outcomes in Heart Failure ... Vericiguat compared with placebo significantly reduced the risk of cardiovascular death or HFH in patients with worsening HF with reduced ejection fraction ...

3. 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 ...

4. withpower.com withpower.com/trial/vericiguat-for-insulin-resistance-2f7ed

Vericiguat for Insulin Resistance · Info for Participants This study is a placebo-controlled randomized trial involving 200 Black obese participants with insulin resistance, assessing the effects of vericiguat on ...

5. jacc.org jacc.org/doi/abs/10.1016/j.jchf.2024.05.007

Vericiguat and Cardiovascular Outcomes in Heart Failure ... Vericiguat compared with placebo significantly reduced the risk of cardiovascular death or HFH in patients with worsening HF with reduced ejection fraction ...

6. ema.europa.eu ema.europa.eu/en/documents/product-information/verquvo-epar-product-information_en.pdf

Verquvo; INN vericiguat - EMA 5.3 Preclinical safety data. Non-clinical data reveal no special hazard for humans based on conventional studies of safety pharmacology, repeated dose ...