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

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

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.

Study Overview

• Status: Terminated
• Conditions: Heart Failure; Cardiomyopathy
• Intervention / Treatment: Drug: POMx, pomegranate polyphenol extract; Drug: Sugar Pill

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.

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • University of Michigan Health System
    • Ann Arbor, Michigan, United States, 48109
      • University of Michigan Health Systems

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: SINGLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: POMx; 15 subjects will received 1000 mg of oral POMx for 12 weeks.	Drug: POMx, pomegranate polyphenol extract; 1000 mg orally once daily.
PLACEBO_COMPARATOR: Control- sugar Pill; 15 subjects will receive a matching sugar pill for 12 weeks.	Drug: Sugar Pill; Matching sugar pill

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Jennifer Cowger , MD, MS
• Collaborators: POM Wonderful LLC
• Investigators: Principal Investigator: Jennifer C Matthews, MD, MS, Univeristy of Michigan Health System; Study Chair: Bertram Pitt, MD, University of Michigan

Study record dates

Study Major Dates

• Study Start: July 1, 2010
• Primary Completion (ACTUAL): May 31, 2013
• Study Completion (ACTUAL): May 31, 2013

Study Registration Dates

• First Submitted: April 12, 2010
• First Submitted That Met QC Criteria: April 12, 2010
• First Posted (ESTIMATE): April 13, 2010

Study Record Updates

• Last Update Posted (ACTUAL): July 14, 2017
• Last Update Submitted That Met QC Criteria: June 13, 2017
• Last Verified: June 1, 2017

More Information

Terms related to this study

• Keywords: Heart Failure; Cardiomyopathy
• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Kidney Diseases; Urologic Diseases; Heart Failure; Renal Insufficiency; Cardiomyopathies
• Other Study ID Numbers: IMPROVEHF

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No