Vericiguat in Patients With Metabolic Syndrome and Coronary Vascular Dysfunction

NCT05711719 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: IRB00310207
• Study Type: interventional
• Target: 45
• Locations: 1 country
• Sites: 1

Brief Summary

Coronary vascular dysfunction is one of the "final common pathways" for the impact of multiple cardiovascular risk factors. The investigators will conduct a randomized, double-blind placebo-controlled study in individuals with the metabolic syndrome and baseline coronary vascular dysfunction to evaluate the impact of vericiguat, a stimulator of soluble guanylyl cyclase, on coronary vascular function using non-invasive cardiac magnetic resonance imaging.

Conditions

Metabolic Syndrome; Coronary Microvascular Dysfunction

Keywords

Cardiac Magnetic Resonance Imaging

Outcome Measures

Primary Outcomes (4)

• Absolute Change in Coronary Cross-sectional Area (in mm²) Within the Vericiguat Group as Assessed by Magnetic Resonance Imaging (MRI)

  The difference in absolute change in coronary cross-sectional area (in mm²) from rest to isometric handgrip exercise (IHE) in the group randomized to vericiguat from that measured at baseline, prior to the initiation of vericiguat, to that measured at the end of the study drug administration period, six weeks following initiation of the titrated dose, as assessed by MRI.

  Baseline and 6 weeks following initiation of up-titrated dose

• Relative Change in Coronary Cross-sectional Area (as Percentage) Within the Vericiguat Group as Assessed by Magnetic Resonance Imaging (MRI)

  The difference in relative change in coronary cross-sectional area (in %) from rest to isometric handgrip exercise (IHE) in the group randomized to vericiguat from that measured at baseline prior to the initiation of vericiguat, to that measured at the end of the study drug administration period, six weeks following initiation of the titrated dose, as assessed by MRI.

  Baseline and 6 weeks following initiation of up-titrated dose

• Absolute Change in Coronary Cross-sectional Area (in mm²) Between the Vericiguat Group and the Placebo Group as Assessed by Magnetic Resonance Imaging (MRI)

  The difference in absolute change in coronary cross-sectional area (in mm²) from rest to isometric handgrip exercise (IHE) as assessed by MRI.

  Baseline and 6 weeks following initiation of up-titrated dose

• Difference in Percent Change in Coronary Cross-sectional Area (as Percentage) Between the Vericiguat Group and the Placebo Group as Assessed by Magnetic Resonance Imaging (MRI)

  The difference in percentage change in coronary cross-sectional area (%) from rest to isometric handgrip exercise (IHE) between the vericiguat and placebo groups, as assessed from the baseline MRI to the follow-up MRI, six weeks following initiation of the titrated dose.

  Baseline and 6 weeks following initiation of up-titrated dose

Secondary Outcomes (16)

• Changes in Interleukin 1 (IL-1) Measured Using Blood Samples (in pg/mL)

  Baseline and 6 weeks following initiation of up-titrated dose

• Changes in Interleukin 6 (IL-6) Measured Using Blood Samples (in pg/mL)

  Baseline and 6 weeks following initiation of up-titrated dose

• Changes in Interleukin 10 (IL-10) Measured Using Blood Samples (in pg/mL)

  Baseline and 6 weeks following initiation of up-titrated dose

• Changes in Tumor Necrosis Factor (TNF)-Alpha Measured Using Blood Samples (in pg/mL)

  Baseline and 6 weeks following initiation of up-titrated dose

• Changes in High Sensitivity C-Reactive Protein (hsCRP) Measured Using Blood Samples (in mg/L)

  Baseline and 6 weeks following initiation of up-titrated dose

Study Arms (2)

Vericiguat

EXPERIMENTAL

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.

Drug: Vericiguat

Placebo

PLACEBO COMPARATOR

A placebo tablet will be administered orally once daily.

Drug: Placebo

Interventions

Vericiguat DRUG

Up-titration will be performed as guided by the evaluation of blood pressure and clinical symptoms

Also known as: Verquvo

Vericiguat

Placebo DRUG

Administered the same way

Placebo

Eligibility Criteria

• Age: 35 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age range 35-85 years
• Presence of the metabolic syndrome defined by the National Cholesterol Education Program, Adult Treatment Panel III (NCEP ATP III) definition, with at least three of the following five criteria:
• waist circumference \> 40 inches (men) or \>35 inches (women)
• blood pressure \>130/80 mmHg
• fasting triglyceride (TG) level \>150 mg/dL
• fasting high-density lipoprotein (HDL) cholesterol level \<40mg/dL in men or \<50mg/dL in women
• Fasting blood glucose \>100 mg/dL, or hemoglobin A1c greater or equal to 5.7%
• Either one of the following:
• Men ≤ 40 or women ≤ 50 years of age with no history or symptoms of ischemic heart disease, or
• Men \>40 or women \>50 years of age with either one of the following
• a coronary angiography within the past 24 months showing no significant coronary artery disease in a t least one major vessel, defined as \>50% stenosis of the left main coronary artery and/or \>70% stenosis of another major coronary vessel, or
• a coronary artery calcium score obtained within the prior 24 months or if no prior calcium scan, one performed as a research study following consent with a Agatston score \<10 in at least one major coronary vessel.
• IHE-induced %-change in coronary flow ≤13%

You may not qualify if:

• Systolic blood pressure \<110 mm Hg
• Current or anticipated use of long-acting nitrates, soluble guanylate cyclase (sGC) stimulators, or phosphodiesterase type 5 (PDE5) inhibitors
• Hematocrit \<30%
• Unable to understand the risks, benefits, and alternatives of participation so as to provide informed consent
• Women who are pregnant.
• Women with reproductive capacity not using an acceptable form of contraception
• History of claustrophobia
• Inability to lie flat and still for 45 minutes
• Presence of non-magnetic resonance (MR)-compatible objects or devices, such as intra-orbital debris, intra-auricular implants, intra-cranial clips, an implanted defibrillator or a pacemaker
• History as a machinist, welder, metal worker or a similar activity that poses the risk of metal exposure to the eyes

Sponsors & Collaborators

• Johns Hopkins University: lead
• Merck Sharp & Dohme LLC: collaborator

Study Sites (1)

Johns Hopkins Hospital

Baltimore, Maryland, 21287, United States

Location

Related Publications (9)

• Tsao CW, Aday AW, Almarzooq ZI, Alonso A, Beaton AZ, Bittencourt MS, Boehme AK, Buxton AE, Carson AP, Commodore-Mensah Y, Elkind MSV, Evenson KR, Eze-Nliam C, Ferguson JF, Generoso G, Ho JE, Kalani R, Khan SS, Kissela BM, Knutson KL, Levine DA, Lewis TT, Liu J, Loop MS, Ma J, Mussolino ME, Navaneethan SD, Perak AM, Poudel R, Rezk-Hanna M, Roth GA, Schroeder EB, Shah SH, Thacker EL, VanWagner LB, Virani SS, Voecks JH, Wang NY, Yaffe K, Martin SS. Heart Disease and Stroke Statistics-2022 Update: A Report From the American Heart Association. Circulation. 2022 Feb 22;145(8):e153-e639. doi: 10.1161/CIR.0000000000001052. Epub 2022 Jan 26.

  PMID: 35078371 BACKGROUND

• Grundy SM, Brewer HB Jr, Cleeman JI, Smith SC Jr, Lenfant C; American Heart Association; National Heart, Lung, and Blood Institute. Definition of metabolic syndrome: Report of the National Heart, Lung, and Blood Institute/American Heart Association conference on scientific issues related to definition. Circulation. 2004 Jan 27;109(3):433-8. doi: 10.1161/01.CIR.0000111245.75752.C6. No abstract available.

  PMID: 14744958 BACKGROUND

• Davignon J, Ganz P. Role of endothelial dysfunction in atherosclerosis. Circulation. 2004 Jun 15;109(23 Suppl 1):III27-32. doi: 10.1161/01.CIR.0000131515.03336.f8.

  PMID: 15198963 BACKGROUND

• Hays AG, Iantorno M, Soleimanifard S, Steinberg A, Schar M, Gerstenblith G, Stuber M, Weiss RG. Coronary vasomotor responses to isometric handgrip exercise are primarily mediated by nitric oxide: a noninvasive MRI test of coronary endothelial function. Am J Physiol Heart Circ Physiol. 2015 Jun 1;308(11):H1343-50. doi: 10.1152/ajpheart.00023.2015. Epub 2015 Mar 27.

  PMID: 25820391 BACKGROUND

• Hays AG, Hirsch GA, Kelle S, Gerstenblith G, Weiss RG, Stuber M. Noninvasive visualization of coronary artery endothelial function in healthy subjects and in patients with coronary artery disease. J Am Coll Cardiol. 2010 Nov 9;56(20):1657-65. doi: 10.1016/j.jacc.2010.06.036.

  PMID: 21050976 BACKGROUND

• Armstrong PW, Roessig L, Patel MJ, Anstrom KJ, Butler J, Voors AA, Lam CSP, Ponikowski P, Temple T, Pieske B, Ezekowitz J, Hernandez AF, Koglin J, O'Connor CM. A Multicenter, Randomized, Double-Blind, Placebo-Controlled Trial of the Efficacy and Safety of the Oral Soluble Guanylate Cyclase Stimulator: The VICTORIA Trial. JACC Heart Fail. 2018 Feb;6(2):96-104. doi: 10.1016/j.jchf.2017.08.013. Epub 2017 Oct 11.

  PMID: 29032136 BACKGROUND

• Jones SP, Bolli R. The ubiquitous role of nitric oxide in cardioprotection. J Mol Cell Cardiol. 2006 Jan;40(1):16-23. doi: 10.1016/j.yjmcc.2005.09.011. Epub 2005 Nov 8.

  PMID: 16288777 BACKGROUND

• Tsai EJ, Kass DA. Cyclic GMP signaling in cardiovascular pathophysiology and therapeutics. Pharmacol Ther. 2009 Jun;122(3):216-38. doi: 10.1016/j.pharmthera.2009.02.009. Epub 2009 Mar 21.

  PMID: 19306895 BACKGROUND

• Stasch JP, Pacher P, Evgenov OV. Soluble guanylate cyclase as an emerging therapeutic target in cardiopulmonary disease. Circulation. 2011 May 24;123(20):2263-73. doi: 10.1161/CIRCULATIONAHA.110.981738. No abstract available.

  PMID: 21606405 BACKGROUND

MeSH Terms

Conditions

Metabolic Syndrome

Interventions

vericiguat

Condition Hierarchy (Ancestors)

Insulin Resistance; Hyperinsulinism; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Results Point of Contact

• Title: Thorsten M. Leucker, MD, PhD
• Organization: Johns Hopkins University

tleucke1@jhmi.edu

(410) 502-9453

Study Officials

• Thorsten M Leucker, M.D., Ph.D.

  Johns Hopkins University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Double-blind, placebo controlled trial

Study Record Dates

• First Submitted: December 6, 2022
• First Posted: February 3, 2023
• Study Start: June 16, 2023
• Primary Completion: November 18, 2025
• Study Completion: November 18, 2025
• Last Updated: January 27, 2026
• Results First Posted: January 27, 2026

Record last verified: 2026-01

Locations

US (1)