The Impact of Pomegranate Extract on Chronic Cardiomyopathy Complicated by Renal Insufficiency (ImPrOVE): a Pilot Study

Study Overview
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Brief Summary
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This blinded, controlled study will examine the impact of pomegranate polyphenol extract (POMx, from Pom Wonderful, LLC), 1000mg on cardiomyopathy in subjects with chronic renal insufficiency.

Detailed Description
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Heart failure (HF) is a disease of great prevalence in the U.S. with an associated high morbidity and mortality. In individuals with concomitant chronic renal insufficiency (CRI), outcomes are even worse due to pharmaceutical under treatment and higher baseline levels of oxidative stress. Reactive oxygen species (ROS) are generated during mechanoenergetic uncoupling and can cause myocardial protein, lipid, and DNA damage, leading to the development of HF. One means of preventing the progression of HF may be through ROS reduction or an improvement in systemic or local oxidative stress handling. In this randomized, single blind placebo-controlled pilot study, we hypothesize that 12 weeks of treatment with oral pomegranate extract (POMx) will lead to a reduction in oxidative stress (as assessed by measuring thiobarbituric acid-reactive substances, F8-isoprostanes, and glutathione) in subjects (n=30) with cardiomyopathy (LVEF ≤40%) and CRI (GFR <60 ml/hr). Secondary aims include assessing the impact of POMx on myocardial remodeling and endothelial dysfunction by measuring serum collagen levels and asymmetric dimethylarginine, respectively. Findings from this study will serve as pilot data for a larger randomized trial of longer term POMx therapy in subjects with cardiomyopathy.

Official Title
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The Impact of Pomegranate (Punica Granatum) Polyphenol Extract on Oxidative Stress, Ventricular Remodeling and Endothelial Function in Chronic Cardiomyopathy Complicated by Renal Insufficiency (ImPrOVE): a Pilot Study

Conditions
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Cardiomyopathy, Heart Failure

Intervention / Treatment
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* Drug: POMx, pomegranate polyphenol extract
* Drug: Sugar Pill


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adult subjects (≥21 years of age) with cardiomyopathy (ejection fraction ≤40%) of at least 1 year duration and CRI (GFR <60 cc/hr for at least 3 months) will be eligible for enrollment. Subjects must have New York Heart Association (NYHA) functional class I-III symptoms and be on stable doses of HF evidence-based therapies (β-blocker, ACE inhibitor or ARBs, aldosterone inhibitor [if appropriate]) for at least 3 months or have a documented contraindication or intolerance to such therapy Exclusion Criteria: Subjects admitted to a hospital for acute myocardial infarction (defined as positive troponins) or HF exacerbation within the last 6 months will not be eligible for enrollment. Subjects on warfarin or rosuvastatin will also be excluded. Other exclusion criteria are as follows: HF that is deemed to be congenital or infiltrative in etiology the presence of a life-threatening illness with a projected survival ≤6 months; ongoing infection pregnancy inability to follow-up end-stage renal disease requiring dialysis renal transplant listing recent (within last 6 months) POMx use or intake >8 ounces daily of pomegranate juice known hypersensitivity to any fruit in the Punicaceae family connective tissue or collagen vascular disease

Ages Eligible for Study
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Minimum Age: 21 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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: POMx<br>15 subjects will received 1000 mg of oral POMx for 12 weeks. | Drug: POMx, pomegranate polyphenol extract<br>* 1000 mg orally once daily.<br>|
| Placebo Comparator: Control- sugar Pill<br>15 subjects will receive a matching sugar pill for 12 weeks. | Drug: Sugar Pill<br>* Matching sugar pill<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Thiobarbituric Reactive Substances (TBARS) | This is a serum marker of oxidative stress. | baseline and after 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| F-8 Isoprostanes | This is a serum marker of oxidative stress. | Baseline and 12 weeks | 
| Procollagen Types I (PINP) and III (PIIINP) | This is a serum marker of collagen turnover (fibrosis/scar formation). | baseline and 12 weeks | 
| Asymmetric Dimethylarginine (ADMA) | ADMA is a serum enzyme involved in metabolism of endothelium derived nitric oxide (NO). NO's has an important role in maintaining endothelial homeostasis. Elevated ADMA levels suggest impaired endothelial function. | baseline and 12 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Cardiomyopathy, Heart Failure