Renal Insufficiency, Chronic, Heart Failure With Preserved Ejection Fraction
Conditions
Brief summary
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
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.
Interventions
DIETARY_SUPPLEMENTMitoQ
4 week 20mg oral daily dose of Mito Q
DIETARY_SUPPLEMENTPlacebo
4 week oral daily dose of TTP placebo
Sponsors
Virginia Commonwealth University
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
OTHER
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Exercise Capacity | Change over 4 weeks | Maximal aerobic capacity (VO2peak) obtained from cardiopulmonary exercise testing |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Reflected Pulse Wave Amplitude | Change over 4 weeks | Late systolic pulsatile load on the left ventricle represented by reflected pulse wave amplitude; assessed by echocardiography combined with applanation tonometry. |
| Forward Pulse Wave Amplitude | Change over 4 weeks | Central hemodynamic assessment of the forward pulse wave amplitude assessed by echocardiography combined with applanation tonometry. |
| Mitochondrial Respiration | Change over 4 weeks | High resolution mitochondrial respirometry |
Countries
United States
Outcome results
None listed