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

Virginia Commonwealth University (VCU)

Status: Completed

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

Treatments: Dietary Supplement: MitoQ; Dietary Supplement: Placebo

Study type: Interventional

Funder types: Other

Identifiers

NCT03960073

HM20015440

Details and patient eligibility

About

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.

Full 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.

Enrollment: 25 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Other

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: Quadruple Blind

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25 participants in 2 patient groups, including a placebo group

MitoQ

Experimental group

Description:

20mg daily oral dose of MitoQ

Treatment:

Dietary Supplement: MitoQ

Placebo

Placebo Comparator group

Description:

Oral TTP placebo

Treatment:

Dietary Supplement: Placebo