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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

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

Conditions
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Renal Insufficiency, Chronic, Heart Failure With Preserved Ejection Fraction

Intervention / Treatment
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* Dietary Supplement: MitoQ
* Dietary Supplement: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: above the age of 18 years a clinical diagnosis of stable Stage C Heart Failure with NYHA Class II-III symptoms a left ventricular ejection fraction >50% Exclusion Criteria: current cancer current pregnancy 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. current antiretroviral medication use absolute contraindications to exercise testing according to the American College of Sports Medicine guidelines fluid overload unable to provide informed consent

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: MitoQ<br>20mg daily oral dose of MitoQ | Dietary Supplement: MitoQ<br>* 4 week 20mg oral daily dose of Mito Q<br>|
| Placebo Comparator: Placebo<br>Oral TTP placebo | Dietary Supplement: Placebo<br>* 4 week oral daily dose of TTP placebo<br>|

What is the study measuring?
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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 |