Cardiomyopathy, Heart Failure
Conditions
Keywords
Cardiomyopathy, Heart Failure
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.
Interventions
DRUGPOMx, pomegranate polyphenol extract
1000 mg orally once daily.
DRUGSugar Pill
Matching sugar pill
Sponsors
POM Wonderful LLC
Jennifer Cowger , MD, MS
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Subject)
Masking description
The participant will either receive POMx or matching placebo (sugar pill)
Eligibility
Sex/Gender
ALL
Age
21 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Thiobarbituric Reactive Substances (TBARS) | baseline and after 12 weeks | This is a serum marker of oxidative stress. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| F-8 Isoprostanes | Baseline and 12 weeks | This is a serum marker of oxidative stress. |
| Procollagen Types I (PINP) and III (PIIINP) | baseline and 12 weeks | This is a serum marker of collagen turnover (fibrosis/scar formation). |
| Asymmetric Dimethylarginine (ADMA) | 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| POMx The POMx subjects received 1000 mg of oral POMx for 12 weeks.
POMx, pomegranate polyphenol extract: 1000 mg orally once daily. | 13 |
| Control- Sugar Pill The control subjects received a matching sugar pill for 12 weeks.
Sugar Pill: Matching sugar pill | 7 |
| Total | 20 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Investigator terminated study | 2 | 2 |
| Overall Study | Lost to Follow-up | 1 | 0 |
Baseline characteristics
| Characteristic | Control- Sugar Pill | Total | POMx |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 2 Participants | 5 Participants | 3 Participants |
| Age, Categorical Between 18 and 65 years | 5 Participants | 15 Participants | 10 Participants |
| Age, Continuous | 58 years | 57 years | 57 years |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) White | 6 Participants | 18 Participants | 12 Participants |
| Region of Enrollment United States | 7 participants | 20 participants | 13 participants |
| Sex: Female, Male Female | 2 Participants | 2 Participants | 0 Participants |
| Sex: Female, Male Male | 5 Participants | 18 Participants | 13 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 13 | 0 / 7 |
| other Total, other adverse events | 0 / 13 | 0 / 7 |
| serious Total, serious adverse events | 0 / 13 | 0 / 7 |
Outcome results
Primary
Thiobarbituric Reactive Substances (TBARS)
This is a serum marker of oxidative stress.
Time frame: baseline and after 12 weeks
Population: Serum samples were obtained and frozen but never analyzed to obtain isoprostane values due to PI departure from study center prior to any batches being sent for analysis.
Secondary
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.
Time frame: baseline and 12 weeks
Population: Serum samples were obtained and frozen but never analyzed to obtain ADMA values due to PI departure from study center prior to any batches being sent for analysis
Secondary
F-8 Isoprostanes
This is a serum marker of oxidative stress.
Time frame: Baseline and 12 weeks
Population: Serum samples were obtained and frozen but never analyzed to obtain isoprostane values due to PI departure from study center prior to any batches being sent for analysis
Secondary
Procollagen Types I (PINP) and III (PIIINP)
This is a serum marker of collagen turnover (fibrosis/scar formation).
Time frame: baseline and 12 weeks
Population: Serum samples were obtained and frozen but never analyzed to obtain procollagen values due to PI departure from study center prior to any batches being sent for analysis