Study of Chokeberry to Reduce Cardiovascular Disease Risk in Former Smokers

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ClinicalTrials.gov Identifier: NCT01541826

Recruitment Status : Completed

First Posted : March 1, 2012

Results First Posted : July 11, 2017

Last Update Posted : July 11, 2017

Sponsor:

Information provided by (Responsible Party):

Bradley Bolling, University of Connecticut

Tracking Information

First Submitted Date ^ICMJE

February 24, 2012

First Posted Date ^ICMJE

March 1, 2012

Results First Submitted Date ^ICMJE

December 12, 2016

Results First Posted Date ^ICMJE

July 11, 2017

Last Update Posted Date

July 11, 2017

Study Start Date ^ICMJE

February 2012

Actual Primary Completion Date

August 2015 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures ^ICMJE

LDL Cholesterol [ Time Frame: Baseline, 6 weeks, 12 weeks of intervention ]

Change in LDL cholesterol from baseline after chronic supplementation. Not determined in Chokeberry Extract Capsule (Acute) arm as this arm was a one-time dose.

Original Primary Outcome Measures ^ICMJE

LDL cholesterol [ Time Frame: Baseline, 6 weeks, 12 weeks of intervention ]

Change in LDL cholesterol from baseline

Change History

Current Secondary Outcome Measures ^ICMJE

Total Cholesterol [ Time Frame: 6 and 12 weeks after supplementation ]
Change in fasting total cholesterol from baseline after chronic supplementation. Not determined in Chokeberry Extract Capsule (Acute) arm as this arm was a one-time dose.
HDL-cholesterol [ Time Frame: 6 and 12 weeks after supplementation ]
Change in fasting plasma cholesterol from baseline after chronic supplemenation. Not determined in Chokeberry Extract Capsule (Acute) arm as this arm was a one-time dose.
Triglycerides [ Time Frame: 6 and 12 weeks after supplementation ]
Change in fasting plasma triglycerides from baseline after chronic supplementation. Not determined in Chokeberry Extract Capsule (Acute) arm as this arm was a one-time dose.
Resting Systolic Blood Pressure [ Time Frame: Baseline, 6 weeks, and 12 weeks following intervention ]
Change in resting systolic blood pressure after chronic supplementation. Not determined in Chokeberry Extract Capsule (Acute) arm as this arm was a one-time dose.
Resting Diastolic Blood Pressure [ Time Frame: Baseline, 6 weeks, and 12 weeks following intervention ]
Change in resting diastolic blood pressure after chronic supplementation. Not determined in Chokeberry Extract Capsule (Acute) arm as this arm was a one-time dose.
Urinary F2-isoprostanes [ Time Frame: Baseline and 12 weeks following intervention ]
Change in resting urinary F2-isoprostanes after chronic supplementation. Not determined in Chokeberry Extract Capsule (Acute) arm as this arm was a one-time dose.
3-hydroxy-3-methyl-glutaryl Coenzyme A Reductase (HMGR) [ Time Frame: Baseline, 12 wk ]
Monocyte messenger ribonucleic acid (mRNA) expression normalized to glyceraldehyde-3-phosphate dehydrogenase (GAPDH) after chronic supplementation. Not determined in Chokeberry Extract Capsule (Acute) arm as this arm was a one-time dose.
LDL Receptor (LDLR) [ Time Frame: Change from baseline at 12 weeks ]
Monocyte LDL receptor mRNA normalized to glyceraldehyde-3-phosphate dehydrogenase after chronic supplementation. Not determined in Chokeberry Extract Capsule (Acute) arm as this arm was a one-time dose.
LDL Receptor (LDLR) Protein [ Time Frame: Baseline, 12 weeks ]
Monocyte LDL receptor protein by Western blot, normalized to β-actin after chronic supplementation. Not determined in Chokeberry Extract Capsule (Acute) arm as this arm was a one-time dose.
Plasma Area Under the Curve of Chokeberry Polyphenols and Their Metabolites. [ Time Frame: 0, 0.5, 1, 2, 4, 6, 9, 12, and 24 hours following dose ]
Plasma area under the curve of chokeberry polyphenols and their metabolites. Measurement (time 0) began at study baseline. Not determined in chronic arms (Color-matched Rice Powder Pill or Chokeberry Extract Capsule).
Urinary Excretion of Polyphenols [ Time Frame: 0 to 24 h after consumption of extract ]
Urinary excretion of polyphenols, from 0 to 24 h after consumption of extract, area under the curve (AUC) in Chokeberry Extract Capsule (acute) arm only.
Adiponectin [ Time Frame: Baseline, 6 weeks, 12 weeks ]
Fasting plasma adiponectin after chronic consumption. Not determined in Chokeberry Extract Capsule (Acute) arm as this arm was a one-time dose.
Interleukin-1 Beta [ Time Frame: Baseline, 6 weeks, 12 weeks ]
Fasting plasma interleukin-1 beta after chronic consumption. Not determined in Chokeberry Extract Capsule (Acute) arm as this arm was a one-time dose.
Interleukin-6 [ Time Frame: Baseline, 6 weeks, 12 weeks ]
Fasting plasma interleukin-6 after chronic supplementation. Not determined in Chokeberry Extract Capsule (Acute) arm as this arm was a one-time dose.
Monocyte Chemoattractant Protein-1 [ Time Frame: Baseline, 6 weeks, 12 weeks ]
Fasting plasma monocyte chemoattractant protein-1 after chronic supplementation. Not determined in Chokeberry Extract Capsule (Acute) arm as this arm was a one-time dose.
Tumor Necrosis Factor-alpha [ Time Frame: Baseline, 6 weeks, 12 weeks ]
Fasting plasma Tumor necrosis factor-alpha after chronic supplementation. Not determined in Chokeberry Extract Capsule (Acute) arm as this arm was a one-time dose.
C-reactive Protein [ Time Frame: Baseline, 6 weeks, 12 weeks ]
Fasting plasma C-reactive protein after chronic supplementation. Not determined in Chokeberry Extract Capsule (Acute) arm as this arm was a one-time dose.
Intercellular Adhesion Molecule 1 [ Time Frame: Baseline, 6 weeks, 12 weeks ]
Fasting plasma intercellular adhesion molecule 1 after chronic supplementation. Not determined in Chokeberry Extract Capsule (Acute) arm as this arm was a one-time dose.
Soluble Vascular Cell Adhesion Molecule 1 [ Time Frame: Baseline, 6 weeks, 12 weeks ]
Fasting plasma soluble vascular cell adhesion molecule 1 after chronic consumption. Not determined in Chokeberry Extract Capsule (Acute) arm as this arm was a one-time dose.
P-selectin [ Time Frame: Baseline, 6 weeks, 12 weeks ]
Fasting plasma P-selectin after chronic supplementation. Not determined in Chokeberry Extract Capsule (Acute) arm as this arm was a one-time dose.
Total Antioxidant Capacity [ Time Frame: Baseline, 6 weeks, 12 weeks ]
Fasting plasma total antioxidant capacity after chronic supplementation. Not determined in Chokeberry Extract Capsule (Acute) arm as this arm was a one-time dose.
Catalase Activity [ Time Frame: Baseline, 6 weeks, 12 weeks ]
Catalase activity after chronic supplementation. Not determined in Chokeberry Extract Capsule (Acute) arm as this arm was a one-time dose.
Glutathione Peroxidase Activity [ Time Frame: Baseline, 6 weeks, 12 weeks ]
Fasting plasma glutathione peroxidase activity after chronic supplementation. Not determined in Chokeberry Extract Capsule (Acute) arm as this arm was a one-time dose.
Superoxide Dismutase Activity [ Time Frame: Baseline, 6 weeks, 12 weeks ]
Fasting plasma superoxide dismutase after chronic supplementation. Not determined in Chokeberry Extract Capsule (Acute) arm as this arm was a one-time dose.
Urinary Polyphenol Excretion [ Time Frame: 12 weeks ]
Overnight urinary polyphenol excretion after chronic supplementation. Not determined in Chokeberry Extract Capsule (Acute) arm as this arm was a one-time dose.
Energy-adjusted Nutrient Intake: Carbohydrate, Protein, Fat, Fiber [ Time Frame: Baseline, 12 weeks ]
Energy-adjusted intake based on 3-day dietary recalls, determined by the average of baseline and 12 weeks. Not determined in Chokeberry Extract Capsule (Acute) arm as this arm was a one-time dose.
Energy Intake [ Time Frame: Baseline, 12 weeks ]
Energy intake reported from 3-day dietary recalls at baseline and 12 weeks, determined by the average of baseline and 12 weeks. Not determined in Chokeberry Extract Capsule (Acute) arm as this arm was a one-time dose.
Energy-adjusted Micronutrient Intake [ Time Frame: Baseline, 12 weeks ]
Energy-adjusted micronutrient intake from 3-day dietary recalls at baseline and 12 weeks. Values reported as the average of baseline and 12 weeks. Not determined in Chokeberry Extract Capsule (Acute) arm as this arm was a one-time dose.
Polyphenol Intake [ Time Frame: Baseline, 12 weeks ]
Energy-adjusted polyphenol intake assessed by 3-day dietary recalls at baseline and 12 weeks, values determined by average of baseline and 12 weeks. Not determined in Chokeberry Extract Capsule (Acute) arm as this arm was a one-time dose.
Intake of Dietary Antioxidant Capacity [ Time Frame: Baseline, 12 weeks ]
Energy-adjusted intake of dietary antioxidant capacity determined by 3-day dietary recalls at baseline and 12 weeks. Values reported as average of baseline and 12 weeks. Not determined in Chokeberry Extract Capsule (Acute) arm as this arm was a one-time dose.
Energy-adjusted Vitamin A Intake [ Time Frame: Baseline, 12 weeks ]
Energy-adjusted vitamin A intake from 3-day dietary recalls at baseline and 12 weeks. Values reported as the average of baseline and 12 weeks. Not determined in Chokeberry Extract Capsule (Acute) arm as this arm was a one-time dose.

Original Secondary Outcome Measures ^ICMJE

Plasma area under the curve of chokeberry polyphenols and their metabolites. [ Time Frame: 0, 0.5, 1, 2, 4, 6, 9, 12, and 24 hours following dose, baseline and 12 weeks ]
Resting systolic blood pressure [ Time Frame: Baseline, 6 weeks, and 12 weeks following intervention ]
Change in resting systolic blood pressure
Resting diastolic blood pressure [ Time Frame: Baseline, 6 weeks, and 12 weeks following intervention ]
Change in resting diastolic blood pressure
Urinary F2-isoprostanes [ Time Frame: Baseline and 12 weeks following intervention ]
Change in resting urinary F2-isoprostanes

Current Other Pre-specified Outcome Measures

Not Provided

Original Other Pre-specified Outcome Measures

Not Provided

Descriptive Information

Brief Title ^ICMJE

Study of Chokeberry to Reduce Cardiovascular Disease Risk in Former Smokers

Official Title ^ICMJE

The Effect of Chokeberry Polyphenols on Biomarkers of Cardiovascular Disease and Antioxidant Defenses in Former Smokers

Brief Summary

The purpose of this project is to determine whether chokeberry polyphenols mitigate cardiovascular disease risk in former smokers.

Detailed Description

More than 31% of Connecticut adults are former smokers, which may contribute to the high cardiovascular disease (CVD) risk in this state. Atherosclerosis, a hallmark of CVD, is a progressive life-long process. Chronic cigarette smoking increases atherosclerosis and CVD risk. While smoking cessation may lower CVD risk, former smokers still are at high CVD risk. The mechanisms by which smoking accelerates atherosclerosis formation are not fully understood. This knowledge gap prevents development of informed interventions to reduce CVD risk in former smokers.

Previous work suggests smoking increases oxidative stress and leads to elevated CVD risk. Former smokers also have decreased antioxidants and markers of vascular function in the circulation, suggesting that despite cessation, smoking has a lingering adverse effect on CVD protective mechanisms. Chokeberry (Aronia melanocarpa) is a native Connecticut plant rich in polyphenol antioxidants and is a promising intervention for reducing CVD risk in former smokers. Chokeberries have diverse polyphenols such as anthocyanins, proanthocyanidins, resveratrol, quercetin, and chlorogenic acid. Chokeberry consumption improves dyslipidemia, inhibits inflammation, and reduces oxidative stress in humans and animals, all of which could contribute to the prevention of CVD in former smokers. Therefore, our central hypothesis is that dietary chokeberry polyphenols reduce CVD risk in former smokers by improving lipid profiles and inhibiting inflammation and oxidative stress. Our long-term goal is to define the mechanisms by which polyphenol antioxidants mitigate CVD risk. The overall goal of this project is to conduct a randomized placebo-controlled clinical trial to evaluate the cardio-protective effects of dietary chokeberry polyphenols in former smokers.

Our objectives are to determine 1) the effect of chokeberry polyphenols on plasma cholesterol and triglyceride levels and on gene expression involved in cholesterol metabolism; 2) the extent to which chokeberry improves antioxidant and vascular function in former smokers; and 3) the association of bioavailability of chokeberry polyphenols to changes in biomarkers of CVD risk.

Successful completion of this work will result in improved understanding of the role of dietary berry polyphenols to regulate lipid metabolism, inflammation and oxidative stress. Thus, this study will be an important step to developing dietary recommendations for individuals predisposed to CVD risk, particularly former smokers.

Study Type ^ICMJE

Interventional

Study Phase ^ICMJE

Not Applicable

Study Design ^ICMJE

Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single (Participant)
Primary Purpose: Basic Science

Condition ^ICMJE

Cardiovascular Disease
Oxidative Stress

Intervention ^ICMJE

Dietary Supplement: Chokeberry Extract
Consumption of 2 x 250 mg chokeberry extract capsules daily for 12 weeks.
Dietary Supplement: Placebo capsule
Color-matched rice powder pill, 2 x 250 mg/day for 12 weeks
Dietary Supplement: Chokeberry extract capsule, acute
Chokeberry extract capsule, 2 x 250 mg, one-time dose.

Study Arms ^ICMJE

Placebo Comparator: Color-matched rice powder pill
Color-matched rice powder pill

Intervention: Dietary Supplement: Placebo capsule
Active Comparator: Chokeberry extract capsule
Chokeberry extract capsule

Intervention: Dietary Supplement: Chokeberry Extract
Experimental: Chokeberry extract capsule (acute)
Chokeberry extract capsule pharmacokinetics

Intervention: Dietary Supplement: Chokeberry extract capsule, acute

Publications *

* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.

Recruitment Information

Recruitment Status ^ICMJE

Completed

Actual Enrollment ^ICMJE

Original Estimated Enrollment ^ICMJE

Actual Study Completion Date ^ICMJE

December 2016

Actual Primary Completion Date

August 2015 (Final data collection date for primary outcome measure)

Eligibility Criteria ^ICMJE

Inclusion Criteria:

Former smoker (previously smoked ≥3 cigarettes/day for at least 1 year, cessation for at least 6 months
Healthy male or female between 18-65 y
Serum clinical ranges no more than mildly elevated (serum cholesterol <240 mg/dL) and serum triglyceride (<150 mg/dL)
Resting blood pressure <140/90 mm Hg
Stable body weight (±5 lb) for last 2 months
BMI ranges within normal and overweight (18.5-39 kg/m2)
Willing to maintain normal exercise level (<7 h/wk)
Willing to avoid exercise 24 h prior to blood sampling
Willing to ingest a dietary chokeberry supplement or placebo (500 mg/d) daily for 12 wks.

Exclusion Criteria:

Previous diagnoses of CVD, diabetes, or arthritis (except for osteo-arthritis)
Currently being treated for cancer (i.e., chemotherapy, radiation therapy)
Women with prescribed estrogen replacement therapy
Practicing slimming diet
Practicing vegetarian diet
Currently taking vitamin or mineral supplements or plant pills
Alcohol consumption exceeding the definition of moderate drinking (2 drinks/day or a total of 12/week for men or 1 drink/day or a total of 7/week for women)

Sex/Gender ^ICMJE

Sexes Eligible for Study:

All

Ages ^ICMJE

18 Years to 65 Years (Adult, Older Adult)

Accepts Healthy Volunteers ^ICMJE

Yes

Contacts ^ICMJE

Contact information is only displayed when the study is recruiting subjects

Listed Location Countries ^ICMJE

United States

Removed Location Countries

Administrative Information

NCT Number ^ICMJE

NCT01541826

Other Study ID Numbers ^ICMJE

H11-311
120068 ( Other Identifier: University of Connecticut )

Has Data Monitoring Committee

U.S. FDA-regulated Product

Not Provided

IPD Sharing Statement ^ICMJE

Not Provided

Current Responsible Party

Bradley Bolling, University of Connecticut

Original Responsible Party

Same as current

Current Study Sponsor ^ICMJE

University of Connecticut

Original Study Sponsor ^ICMJE

Same as current

Collaborators ^ICMJE

Not Provided

Investigators ^ICMJE

Principal Investigator:

Bradley W Bolling, PhD

University of Connecticut, University of Wisconsin-Madison

PRS Account

University of Connecticut

Verification Date

April 2017

^ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP

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