Inorganic NItrate and EXercise Performance in Heart Failure (iNIX-HF): Dose Response

NCT02797184 | Completed Phase 1 Results DMC FDA Drug

• 1 other identifier: 2016_11111
• Study Type: interventional
• Target: 42
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to do the work that is necessary and sufficient for setting up an appropriate multi-center, randomized clinical trial (RCT) of a new therapy for heart failure: inorganic nitrate. The investigators will first determine the effects and palatability of \~12.8mmol KNO3 (an oral pill) as compared to the roughly equivalent amount of nitrate in 2 beetroot juice (BRJ) Sports Shots (by James White Drinks). Next, the investigators will determine the effects of inorganic nitrate (KNO3 in an oral pill format) on blood pressure, blood nitrate levels, breath nitric oxide (NO) levels, and exercise performance in a dose-response study. Third, the investigators will perform a small phase II chronic treatment study that will allow them to determine the best primary endpoint and the numbers of patients the investigators will need to study in the large, multi-center RCT to follow this project. In the small study and in the RCT to follow, the investigators will determine whether inorganic nitrate can improve aerobic exercise capacity, muscle power, and speed of muscle contraction, and lessen the effort of breathing during exercise.

Conditions

Heart Failure

Outcome Measures

Primary Outcomes (1)

• VO2peak

  peak oxygen consumption during treadmill exercise

  acute - 2.5 hours post dose

Secondary Outcomes (3)

• Peak Muscle Power

  acute - 2 hours post dose

• Blood Nitrite Levels

  time 0 (before receiving the KNO3 dose) and hourly after receiving KNO3 (1, 2, and 3 hours post-dose)

• Breath Nitric Oxide (NO) Level

  time 0 (before receiving the KNO3 dose) and hourly after receiving KNO3 (1, 2, and 3 hours post-dose)

Study Arms (2)

10mmol KNO3

EXPERIMENTAL

Intervention: Subjects with heart failure will receive a single oral dose of potassium nitrate (10 or 20 mmol KNO3) in 2 gelatin capsules during dose visit 1 and the other dose (10 or 20 mmol KNO3) during dose visit 2. The dose order will be randomized.

Drug: KNO3, potassium nitrate

20mmol KNO3

EXPERIMENTAL

Intervention: Subjects with heart failure will receive a single oral dose of potassium nitrate (10 or 20 mmol KNO3) in 2 gelatin capsules during dose visit 1 and the other dose (10 or 20 mmol KNO3) during dose visit 2. The dose order will be randomized.

Drug: KNO3, potassium nitrate

Interventions

KNO3, potassium nitrate DRUG

Potassium nitrate (KNO3) will be given orally in 2 gelatin capsules, which will be compounded by the Barnes-Jewish Hospital Pharmacy. The doses are 10 mmol and 20 mmol KNO3.

Also known as: saltpeter

10mmol KNO3; 20mmol KNO3

Eligibility Criteria

• Age: 18 Years - 74 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Sex: females and males
• Age: at least 18 years and less than 75 years
• Diagnosis of heart failure with reduced ejection fraction (NYHA II-IV)
• Ejection fraction \<45% as determined on an imaging study within 12 mo of enrollment
• Stable medical therapy - defined by no addition or removal (or change of more than 100%) of the following: beta-adrenergic blockade, angiotensin converting enzyme (ACE) inhibitors, or angiotensin receptor blocker (ARB or aldosterone antagonists) for 30 days prior to enrolment

You may not qualify if:

• "Vulnerable populations" as defined by the U.S. Department of Health and Human Services, such as prisoners and children
• Pharmacologic, organic nitrate therapy within the last 3 months
• Major orthopedic, psychiatric, neurological, or other conditions that would impair performance of the exercise tests in this study
• Atrial fibrillation/flutter
• Estimated glomerular filtration rate \< 50 ml/min on most recent clinical laboratories
• Systolic blood pressure \< 95 mmHg or \>180 mmHg at consent
• Diastolic blood pressure \<40 mmHg or \>100 mmHg at consent
• Previous adverse reaction to nitrates necessitating withdrawal of therapy
• Treatment with phosphodiesterase inhibitors within the last 3 months (patient must also be willing to not take them for the duration of the trial).
• Ejection fraction \> 45%
• Primary hypertrophic cardiomyopathy
• Infiltrative cardiomyopathy (e.g., amyloid)
• Active myocarditis
• Complex congenital heart disease
• Active collagen vascular disease

Sponsors & Collaborators

• Washington University School of Medicine: lead

Study Sites (1)

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

MeSH Terms

Conditions

Heart Failure

Interventions

potassium nitrate

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases

Results Point of Contact

• Title: Dr. Lauren Park
• Organization: Washington University in St. Louis

l.park@wustl.edu

3143633915

Study Officials

• Linda R Peterson, MD

  Washington University School of Medicine

  PRINCIPAL INVESTIGATOR

• Andrew R Coggan, PhD

  Washington University School of Medicine

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: Both the participant and the investigator will be masked to which KNO3 dose is administered at each visit. However, it is known at the outset that each patient will receive 10 mmol KNO3 during one visit and 20 mmol KNO3 at another visit, with the order randomly assigned.
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Subjects will receive one drug dose on the first dose visit and the second drug dose on the second dose visit. The order of the two drug doses (10 and 20 mmol KNO3) will be randomized, so that some subjects will receive the lower dose first and others will receive the higher dose first

Study Record Dates

• First Submitted: May 25, 2016
• First Posted: June 13, 2016
• Study Start: October 31, 2017
• Primary Completion: October 31, 2021
• Study Completion: December 15, 2021
• Last Updated: May 20, 2025
• Results First Posted: February 10, 2023

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will share

Locations

US (1)