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Study of Chokeberry to Reduce Cardiovascular Disease Risk in Former Smokers

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
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
 (submitted: April 12, 2017)
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
 (submitted: February 29, 2012)
LDL cholesterol [ Time Frame: Baseline, 6 weeks, 12 weeks of intervention ]
Change in LDL cholesterol from baseline
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: April 12, 2017)
  • 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
 (submitted: February 29, 2012)
  • 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
 (submitted: April 12, 2017)
62
Original Estimated Enrollment  ICMJE
 (submitted: February 29, 2012)
66
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 No
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