Enhancing the Natriuretic Peptide System in HFpEF

NCT05279742 | Enrolling By Invitation Phase 1 FDA Drug

• 1 other identifier: 21-008978
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to look at the differences in how individuals with heart failure with preserved ejection fraction in the presence of chronic kidney disease (HFpEF-CKD) and exercise induced dyspnea without objective findings of fluid retention (HFpEF-EI) bodies function using drugs Sacubatril/Valsartan (Entresto) and MANP.

Conditions

Heart Failure With Preserved Ejection Fraction; Chronic Kidney Diseases

Keywords

Exercise Induced Dyspnea

Outcome Measures

Primary Outcomes (2)

• Change in Plasma ANP

  Change in Plasma ANP (pg/ml) level after administration of study drug/placebo compared to baseline in response to volume expansion in HFpEF-EI vs HFpEF-CKD.

  24 hours

• Change in Composite Score of cGMP, sodium excretion, GFR, and Anx-A1 Plasma cGMP, urinary cGMP, urinary sodium excretion, GFR, ANX-A1acute VE with MANP

  A composite score of change in urinary cGMP (pmol/min), sodium excretion (mEq/min), GFR (ml/min), and Anx-A1 (pg/ml) after administration of study drug/placebo compared to baseline in response to volume expansion in HFpEF-EI vs HFpEF-CKD within each treatment group.

  24 hours

Secondary Outcomes (2)

• Change in Plasma NT-pro BNP

  24 hours

• Change in Plasma cGMP

  24 hours

Study Arms (6)

HFpEF-CKD with MANP and oral placebo

EXPERIMENTAL

Subjects with with HFpEF volume overload in the presence of chronic kidney diseases and clinical symptoms at rest (e.g. peripheral edema, weight gain, and abdominal distention) will receive study drug MANP and an oral placebo followed by a 1 week washout period.

Drug: MANP; Drug: Oral Placebo

HFpEF-EI with MANP and oral placebo

EXPERIMENTAL

Subjects with with HFpEF with exercise induced dyspnea (difficult or labored breathing) without clinical symptoms at rest (e.g. peripheral edema, weight gain, and abdominal distention) will receive study drug MANP and an oral placebo followed by a 1 week washout period.

Drug: MANP; Drug: Oral Placebo

HFpEF-CKD with Sacbitril/Valsartan with an injected placebo

EXPERIMENTAL

Subjects with with HFpEF volume overload in the presence of chronic kidney diseases and clinical symptoms at rest (e.g. peripheral edema, weight gain, and abdominal distention) will receive study drug Sacbitril/Valsartan and an injected placebo followed by a 1 week washout period.

Drug: Sacubitril/Valsartan; Drug: Injection Placebo

HFpEF-EI with Sacbitril/Valsartan with an injected placebo

EXPERIMENTAL

Subjects with with HFpEF with exercise induced dyspnea (difficult or labored breathing) without clinical symptoms at rest (e.g. peripheral edema, weight gain, and abdominal distention) will receive study drug Sacbitril/Valsartan and an injected placebo followed by a 1 week washout period.

Drug: Sacubitril/Valsartan; Drug: Injection Placebo

HFpEF-CKD with an oral and injected placebo

PLACEBO COMPARATOR

Subjects with with HFpEF volume overload in the presence of chronic kidney diseases and clinical symptoms at rest (e.g. peripheral edema, weight gain, and abdominal distention) will receive an oral and injected placebo followed by a 1 week washout period.

Drug: Oral Placebo; Drug: Injection Placebo

HFpEF-EI with an oral and injected placebo

PLACEBO COMPARATOR

Subjects with with HFpEF with exercise induced dyspnea (difficult or labored breathing) without clinical symptoms at rest (e.g. peripheral edema, weight gain, and abdominal distention) will receive an oral and injected placebo followed by a 1 week washout period.

Drug: Oral Placebo; Drug: Injection Placebo

Interventions

MANP DRUG

Single subcutaneous injection 5 µg/Kg

HFpEF-CKD with MANP and oral placebo; HFpEF-EI with MANP and oral placebo

Sacubitril/Valsartan DRUG

Oral single dose 97/103 mg

Also known as: Entresto

HFpEF-CKD with Sacbitril/Valsartan with an injected placebo; HFpEF-EI with Sacbitril/Valsartan with an injected placebo

Oral Placebo DRUG

Oral single dose that contains no active ingredient

HFpEF-CKD with MANP and oral placebo; HFpEF-CKD with an oral and injected placebo; HFpEF-EI with MANP and oral placebo; HFpEF-EI with an oral and injected placebo

Injection Placebo DRUG

Single subcutaneous injection that contains no active ingredient

HFpEF-CKD with Sacbitril/Valsartan with an injected placebo; HFpEF-CKD with an oral and injected placebo; HFpEF-EI with Sacbitril/Valsartan with an injected placebo; HFpEF-EI with an oral and injected placebo

Eligibility Criteria

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

You may qualify if:

• Group 1: HFpEF-CKD-will consist of 30 subjects with:
• Ejection fraction of equal or greater than 55%; and
• Evidence of increased LV filling pressures, including at least 2 of the following: average septal-lateral E/e' ratio ≥ 15; tricuspid regurgitation (TR) peak velocity \> 2:8 m/s;
• Left atrial volume index \>34mL/m\^2 assessed by echocardiography; and
• Previous diagnosis of HF with New York Heart Association (NYHA) functional class II-III symptoms on chronic diuretic therapy; and

You may not qualify if:

• Group 2: HFpEF-EI-will consist of 30 subjects with:
• Ejection fraction of equal or greater than 55%; and
• Previous invasive determination of normal pulmonary capillary wedge pressure ≤ 15 mmHg) at rest and ≥ 25 mmHg during exercise; and
• New York Heart Association (NYHA) functional class II-III symptoms; and
• Body mass index \> 35.
• Blood pressure \< 100/60 or \> 180/100 mmHg.
• Diabetes.
• Myocardial infarction within 6 months of screening.
• Unstable angina within 6 months of screening, or any evidence of myocardial ischemia.
• Significant valvular heart diseases.
• Hypertrophic, restrictive or obstructive cardiomyopathy.
• Constrictive pericarditis.
• Primary pulmonary hypertension.
• Biopsy proven active myocarditis.
• Severe congenital heart diseases.

Sponsors & Collaborators

• Horng Chen: lead

Study Sites (1)

Mayo Clinic in Rochester

Rochester, Minnesota, 55905, United States

Location

MeSH Terms

Conditions

Renal Insufficiency, Chronic

Interventions

sacubitril and valsartan sodium hydrate drug combination

Condition Hierarchy (Ancestors)

Renal Insufficiency; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Paul M McKie

  Mayo Clinic

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Regulatory Sponsor

Study Record Dates

• First Submitted: March 4, 2022
• First Posted: March 15, 2022
• Study Start: November 4, 2022
• Primary Completion (Estimated): April 1, 2027
• Study Completion (Estimated): April 1, 2027
• Last Updated: October 9, 2025

Record last verified: 2025-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)