Chronic Kidney Disease and Heart Failure With Preserved Ejection Fraction: The Role of Mitochondrial Dysfunction

The purpose of this study is to investigate the role of mitochondrial derived oxidative stress on exercise capacity and arterial hemodynamics in HFpEF patients with and without chronic kidney disease.

Study Overview

• Status: Completed
• Conditions: Renal Insufficiency, Chronic; Heart Failure With Preserved Ejection Fraction
• Intervention / Treatment: Dietary supplement: MitoQ; Dietary supplement: Placebo

Detailed Description

Heart failure is a public health epidemic affecting 6.5 million Americans. Heart failure with preserved ejection fraction (HFpEF) accounts for a large burden of heart failure with the incidence and cost associated with the disease projected to double in the next 20 years. The pathophysiology of HFpEF has not yet been fully elucidated and no proven therapies for improving outcomes in HFpEF currently exist, posing major diagnostic and therapeutic challenges. The addition of chronic kidney disease (CKD) presents a complicated cardio renal syndrome that manifests a distinctly different phenotype and exacerbates the diagnostic and therapeutic challenges of HFpEF. This study aims to address the urgent need to establish treatment targets and therapies by investigating potential underlying biological contributors to HFpEF and its symptoms.

Mitochondrial dysfunction is consistently reported in CKD and heart failure. Mitochondrial dysfunction has been implicated in cardiac, skeletal muscle and vascular dysfunction and is therefore an attractive target for a 'whole systems' therapeutic approach that would encompass exercise intolerance and abnormal blood vessel hemodynamics. A known contributor to and subsequent cyclical result of mitochondrial dysfunction is an abnormally heightened production of mitochondria derived oxidative stress. This study will address the role of mitochondria derived oxidative stress in mitochondrial dysfunction, exercise intolerance and large blood vessel hemodynamics HFpEF patients with and without CKD.

• Study Type: Interventional
• Enrollment (Actual): 25
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Danielle L Kirkman, PhD; Phone Number: 8048272386; Email: dlkirkman@vcu.edu

Study Locations

• United States
  • Virginia
    • Richmond, Virginia, United States, 23298-0256
      • Virginia Commonwealth University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. above the age of 18 years
2. a clinical diagnosis of stable Stage C Heart Failure with NYHA Class II-III symptoms
3. a left ventricular ejection fraction >50%

Exclusion Criteria:

1. current cancer
2. current pregnancy
3. current antioxidant supplement use and unwilling to have a 7-day antioxidant washout period before the beginning the trial and to continue antioxidant disuse throughout the trial.
4. current antiretroviral medication use
5. absolute contraindications to exercise testing according to the American College of Sports Medicine guidelines
6. fluid overload
7. unable to provide informed consent

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: MitoQ; 20mg daily oral dose of MitoQ	Dietary supplement: MitoQ; 4 week 20mg oral daily dose of Mito Q
Placebo Comparator: Placebo; Oral TTP placebo	Dietary supplement: Placebo; 4 week oral daily dose of TTP placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Exercise Capacity	Maximal aerobic capacity (VO2peak) obtained from cardiopulmonary exercise testing	Change over 4 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Reflected Pulse Wave Amplitude	Late systolic pulsatile load on the left ventricle represented by reflected pulse wave amplitude; assessed by echocardiography combined with applanation tonometry.	Change over 4 weeks
Forward Pulse Wave Amplitude	Central hemodynamic assessment of the forward pulse wave amplitude assessed by echocardiography combined with applanation tonometry.	Change over 4 weeks
Mitochondrial Respiration	High resolution mitochondrial respirometry	Change over 4 weeks

Collaborators and Investigators

• Sponsor: Virginia Commonwealth University
• Investigators: Principal Investigator: Danielle L Kirkman, PhD, Virginia Commonwealth University

Study record dates

Study Major Dates

• Study Start (Actual): July 31, 2019
• Primary Completion (Actual): September 30, 2022
• Study Completion (Actual): September 30, 2022

Study Registration Dates

• First Submitted: May 20, 2019
• First Submitted That Met QC Criteria: May 20, 2019
• First Posted (Actual): May 22, 2019

Study Record Updates

• Last Update Posted (Actual): December 19, 2022
• Last Update Submitted That Met QC Criteria: December 15, 2022
• Last Verified: December 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Urologic Diseases; Heart Failure; Kidney Diseases; Renal Insufficiency, Chronic; Renal Insufficiency
• Other Study ID Numbers: HM20015440

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No