Clinical trial NCT01102140: The Impact of Pomegranate Extract on Chronic Cardiomyopathy Complicated by Renal Insufficiency (ImPrOVE): a Pilot Study
Official title: 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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Cardiomyopathy
Heart Failure
Keywords: Cardiomyopathy
Heart Failure
Lead sponsor: University of Michigan
Sponsor class: OTHER
Collaborators: name: POM Wonderful LLC
First posted: 2010-04-13
Enrollment: 20
Sex: ALL
Minimum age (years): 21
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Thiobarbituric Reactive Substances (TBARS)
timeFrame: baseline and after 12 weeks
Secondary outcomes:
measure: F-8 Isoprostanes
timeFrame: Baseline and 12 weeks
measure: Procollagen Types I (PINP) and III (PIIINP)
timeFrame: baseline and 12 weeks
measure: Asymmetric Dimethylarginine (ADMA)
timeFrame: baseline and 12 weeks
Other outcomes:
Locations:
city: Ann Arbor
country: United States
facility: University of Michigan Health Systems
state: Michigan
city: Ann Arbor
country: United States
facility: University of Michigan Health System
state: Michigan
Study officials:
affiliation: Univeristy of Michigan Health System
name: Jennifer C Matthews, MD, MS
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Michigan
name: Bertram Pitt, MD
role: STUDY_CHAIR
References: