Oral Nitrite for Older Heart Failure With Preserved Ejection Fraction

NCT02918552 | Completed Phase 2 Results FDA Drug

• 2 other identifiers: STUDY190704501R56AG051637-01A1
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

Brief Summary

This is a randomized double blinded controlled trial of 20-40 mg sodium nitrite tid in subjects with HFpEF. Primary outcomes are measures of physical function with non-invasive and invasive cardiopulmonary exercise testing, and fatigability, skeletal muscle bioenergetics, serology including inflammatory markers and platelet bioenergetics, quality of life measures.

Conditions

Heart Failure

Outcome Measures

Primary Outcomes (1)

• Cardiorespiratory Fitness

  Assessment of peak Oxygen uptake (VO2) maximum via symptom limited exercise testing

  Week 2(pre drug) to Week 10( post drug); approx. 8 weeks

Secondary Outcomes (14)

• Perceived Fatigability

  Week 2(pre drug) to Week 10( post drug); approx. 8 weeks

• Bioenergetics: In-Vivo 31P MRS Respirations

  Week 3 (pre drug) to week 10(post drug); approx. 8 weeks

• Bioenergetics: Ex-Vivo Mitochondrial Respiration Analysis

  Week 5 (pre-drug) to week 16 (post-drug); approx. 8 weeks

• Exercise-induced Changes in Pulmonary Arterial Pressure

  Week 3 (pre-drug) to week 10 (post drug); approx 8 weeks

• Exercise-induced Changes in Pulmonary Capillary Wedge Pressure

  Week 3 (pre-drug) to week 10 (post drug); approx 8 weeks

Other Outcomes (27)

• Adiponectin

  Week 5 (pre drug) to week 16 (post drug); approx. 8 weeks

• Blood Nitrate

  Week 5 (pre drug) to week 16 (post drug); approx. 8 week

• Brain Natriuretic Protein

  Week 5 (pre drug) to week 16 (post drug); approx. 8 weeks

Study Arms (2)

Treatment

EXPERIMENTAL

20 or 40 mg sodium nitrite tid

Drug: sodium nitrite

Control

PLACEBO COMPARATOR

20 or 40 mg placebo tid

Drug: Control

Interventions

sodium nitrite DRUG

Subjects to receive active study drug three times daily during treatment period and then post treatment testing period.

Also known as: nitrite

Treatment

Control DRUG

Subjects randomized to placebo to receive three times daily during treatment period and then post treatment testing period.

Also known as: Placebo

Control

Eligibility Criteria

• Age: 70 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Older Adult (65+)

You may qualify if:

• Age ≥70 years
• Diagnosis of HFpEF \[adapted from the 2016 European Society of Cardiology (ESC) Guidelines to include:
• \. Prior diagnosis of HF via one of these:
• medical record diagnosis by attending cardiologist
• verbal confirmation of HFpEF with attending cardiologist
• PI review of medical record to confirm HFpEF AND 2. Ejection Fraction % ≥40
• Clinically stable (euvolemic; baseline heart rate \<100 bpm) and without hospitalization or invasive cardiac procedure for 6 weeks
• Patients using 81 milligram (mg) aspirin (ASA) will be eligible, but will be asked to hold the medication for 3 days prior to biopsy. This technique has previously been used with consistent safety. Patients will also be asked to avoid non-steroidal anti-inflammatory medications (NSAIDs) for 2 days prior to the biopsy.
• Patients using anti-thrombin and anti-platelet therapy will plan to modify prior to muscle biopsies individually in coordination with the participant's primary cardiologist.

You may not qualify if:

• Allergy to lidocaine
• BP \>180/95 or \<100/60
• Anemia: Hgb\<11.0 (♂),10.0 (♀)
• Dementia or inability to give informed consent
• End-stage malignancy
• Severe orthopedic exercise limitation
• Use of chronic oral corticosteroids or other medications that affect muscle function.
• Chronic alcohol or drug dependency.
• Any bleeding disorder that would contraindicate biopsy such as history of clinically significant bleeding diathesis (e.g., Hemophilia A or B, Von Willebrand's Disease or congenital Factor VII deficiency).
• Psychiatric hospitalization within the last 3 months
• Major cardiovascular event or procedure within the prior 6 weeks
• HF secondary to significant uncorrected primary valvular disease (except mitral regurgitation secondary to left ventricular dysfunction). If valve replacement has been performed, patient may not be enrolled for 12 months after this procedure.
• Severe uncorrected primary valvular heart disease (if valve replacement has been performed, patients will not be eligible for at least 12 months)
• Mechanical valve replacement requiring warfarin
• Peripheral or pulmonary artery disease

Sponsors & Collaborators

• Gladwin, Mark, MD: lead
• National Institute on Aging (NIA): collaborator

Study Sites (1)

UPMC Montefiore Hospital

Pittsburgh, Pennsylvania, 15213, United States

Location

MeSH Terms

Conditions

Heart Failure

Interventions

Sodium Nitrite; Nitrites

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Nitrous Acid; Nitrogen Compounds; Inorganic Chemicals; Sodium Compounds; Anions; Ions; Electrolytes; Organic Chemicals

Limitations and Caveats

Magnetic Resonance Spectroscopy, Oroboros, and invasive CPET equipment unexpectedly had limited availability.

Results Point of Contact

• Title: Tara Sheila Stakich
• Organization: University of Pittsburgh

tss54@pitt.edu

412-864-2082

Study Officials

• Daniel E Forman, MD

  University of Pittsburgh

  PRINCIPAL INVESTIGATOR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDIV
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: September 13, 2016
• First Posted: September 29, 2016
• Study Start: April 3, 2017
• Primary Completion: December 2, 2018
• Study Completion: December 31, 2018
• Last Updated: January 22, 2020
• Results First Posted: January 22, 2020

Record last verified: 2020-01

Data Sharing

• IPD Sharing: Will share
• Time Frame: A limit in time frame for sharing has not been defined.
• Access Criteria: Only de-identified data approved for sharing by the PI.

Locations

US (1)