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

• ClinicalTrials.gov Identifier: NCT01102140
• Recruitment Status: Terminated
• First Posted: April 13, 2010
• Results First Posted: July 14, 2017
• Last Update Posted: July 14, 2017
• Sponsor: Jennifer Cowger , MD, MS
• Collaborator: POM Wonderful LLC
• Information provided by (Responsible Party): Jennifer Cowger , MD, MS, University of Michigan

Tracking Information

• First Submitted Date: April 12, 2010
• First Posted Date: April 13, 2010
• Results First Submitted Date: May 18, 2017
• Results First Posted Date: July 14, 2017
• Last Update Posted Date: July 14, 2017
• Study Start Date: July 2010
• Actual Primary Completion Date: May 31, 2013 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: June 13, 2017)

Thiobarbituric Reactive Substances (TBARS) [ Time Frame: baseline and after 12 weeks ]

This is a serum marker of oxidative stress.

• Original Primary Outcome Measures (submitted: April 12, 2010): thiobarbituric reactive substances (TBARS) [ Time Frame: baseline and after 12 weeks ]

Current Secondary Outcome Measures (submitted: June 13, 2017)

• F-8 Isoprostanes [ Time Frame: Baseline and 12 weeks ]
  This is a serum marker of oxidative stress.
• Procollagen Types I (PINP) and III (PIIINP) [ Time Frame: baseline and 12 weeks ]
  This is a serum marker of collagen turnover (fibrosis/scar formation).
• Asymmetric Dimethylarginine (ADMA) [ Time Frame: baseline and 12 weeks ]
  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.

Original Secondary Outcome Measures (submitted: April 12, 2010)

• F-8 isoprostanes [ Time Frame: Baseline and 12 weeks ]
• procollagen types I (PINP) and III (PIIINP) [ Time Frame: baseline and 12 weeks ]
• asymmetric dimethylarginine (ADMA) [ Time Frame: baseline and 12 weeks ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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
• 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.
• Study Type: Interventional
• Study Phase: Phase 2

Study Design

Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single (Participant)
Masking Description:

The participant will either receive POMx or matching placebo (sugar pill)

Primary Purpose: Treatment

Condition

• Cardiomyopathy
• Heart Failure

Intervention

• Drug: POMx, pomegranate polyphenol extract
  1000 mg orally once daily.
• Drug: Sugar Pill
  Matching sugar pill

Study Arms

• Active Comparator: POMx
  15 subjects will received 1000 mg of oral POMx for 12 weeks.
  Intervention: Drug: POMx, pomegranate polyphenol extract
• Placebo Comparator: Control- sugar Pill
  15 subjects will receive a matching sugar pill for 12 weeks.
  Intervention: Drug: Sugar Pill

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Terminated
• Actual Enrollment (submitted: June 13, 2017): 20
• Original Estimated Enrollment (submitted: April 12, 2010): 30
• Actual Study Completion Date: May 31, 2013
• Actual Primary Completion Date: May 31, 2013 (Final data collection date for primary outcome measure)

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 21 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT01102140
• Other Study ID Numbers: IMPROVEHF
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No

IPD Sharing Statement

• Plan to Share IPD: Undecided

• Current Responsible Party: Jennifer Cowger , MD, MS, University of Michigan
• Original Responsible Party: Jennifer Cowger Matthews, MD, MS, University of Michigan Health Systems
• Current Study Sponsor: Jennifer Cowger , MD, MS
• Original Study Sponsor: University of Michigan
• 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

• PRS Account: University of Michigan
• Verification Date: June 2017