The Health Effects of Blueberry Anthocyanins in Metabolic Syndrome (the CIRCLES-study)

Study Overview
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Brief Summary
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The purpose of this study is to determine the dose-dependent impact of 6 month freeze-dried blueberry powder intake on insulin sensitivity and resistance, cardiovascular disease risk factors, and lung and cognitive function in overweight and obese participants with metabolic syndrome. We will also examine acute post-prandial effects of blueberry intake (at baseline and at 6-months).

Official Title
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The Effects of Blueberry Anthocyanins on Insulin Resistance and Vascular, Lung and Cognitive Function in a Population With Metabolic Syndrome.

Conditions
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Insulin Resistance, Metabolic Syndrome X

Intervention / Treatment
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* Other: Full dose blueberry
* Other: Half dose blueberry
* Other: Control


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Men and postmenopausal women (≥ 1 year since last menstruation) 50 to 75 years old BMI of ≥ 25 kg/m2 3 characteristics of metabolic syndrome i.e: Waist circumference ≥ 102 cm for men, ≥ 88 cm for women; Triglycerides ≥ 1.7 mmol/L (or drug treatment for elevated triglycerides); HDL-cholesterol < 1.0 mmol/L for men, < 1.3 mmol/L for women (or drug treatment for low HDL-cholesterol); Blood pressure ≥ 130 mm Hg systolic and/or ≥ 85 mm Hg diastolic blood pressure; Fasting blood glucose ≥ 5.56 mmol/L Successful biochemical, haematological and urinalysis assessment at screening Exclusion Criteria: Current smokers, or ex-smokers ceasing < 6 months ago Existing or significant past medical history of vascular disease or medical conditions likely to affect the study measures Fructose intolerance or known allergies to the intervention treatments On therapeutic diets or having experienced substantial weight loss within 3 months of screening Taking flavonoid containing supplements (and unwilling to cease intake during, and 1 month preceding the trial) Planning on altering consumption of vitamin supplements / fish oil capsules during the course of the study. Prescribed hypoglycaemic, vasodilators or HRT medication. Unsatisfactory biochemical, haematological or urinary assessment at screening, or measures considered to be counter indicative for the study < 3 characteristics of the metabolic syndrome. NB: REC approved NoSA granted to include those on anti-hypertensives (29JUL2014)

Ages Eligible for Study
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Minimum Age: 50 Years
Maximum Age: 74 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Full dose blueberry<br>26g of freeze dried blueberry powder; equivalent to 2 portions of fresh blueberries per day. Frequency: 26g per day. Total duration: 6-month. | Other: Full dose blueberry<br>* Full dose: 26g of freeze dried blueberry powder to be incorporated into the habitual diet. Dietary restrictions will be observed (i.e. avoidance of blueberry, and restricted intake of anthocyanin rich foods) for 21 days prior to the first assessment visit and throughout the study.<br>|
| Active Comparator: Half dose blueberry<br>26g of freeze dried powder; containing 13g of freeze dried blueberry powder and 13g of placebo comparator material; equivalent to 1 portion of fresh blueberries per day. Frequency: 26g per day. Total duration: 6-month. | Other: Half dose blueberry<br>* Half dose: 26g of freeze dried powder (containing 13g of freeze dried blueberry powder and 13g of placebo comparator material) to be incorporated into the habitual diet. Dietary restrictions will be observed (i.e. avoidance of blueberry, and restricted intake of anthocyanin rich foods) for 21 days prior to the first assessment visit and throughout the study.<br>|
| Placebo Comparator: Control<br>Matched control powder; matched for appearance, taste and sugar content. Frequency: 26g per day. Total duration: 6-month. | Other: Control<br>* Control: 26g of placebo comparator material to be incorporated into the habitual diet. Dietary restrictions will be observed (i.e. avoidance of blueberry, and restricted intake of anthocyanin rich foods) for 21 days prior to the first assessment visit and throughout the study.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Insulin resistance | Assessed, in the fasted state, via HOMA-IR calculation in all participants; indirect assessment. | Chronic (0 to 6 month) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Insulin resistance | Assessed in a sub-group via hyperinsulinemic euglycaemic clamp. | Chronic (0 to 6 month) | 
| Blood pressure and blood vessel regulation | Measurements taken of arterial stiffness, endothelial function and blood pressure. | Chronic (0 to 6 month) | 
| Lung function | Assessed via standard spirometry techniques and biological assessment of exhaled samples. | Chronic (0 to 6 month) | 
| Cognitive function | Assessed via a validated cognitive test battery. | Chronic (0 to 6 month) | 
| Liver fat and blood flow assessment | Assessment via 3T MRI in a sub-group of participants. | Chronic (0 to 6 month) | 
| Bio-availability | Flavonoid and metabolite levels will be assessed in blood and 24 hour urine samples. | Chronic (0 to 6 month) | 
| Metabolite phenotype effects | The gut microbiome will be assessed from faecal sample collection and the impact on metabolism and of genotype, will be assessed via a targeted approach. | Chronic (0 to 6 month) | 
| Acute +24 hour effect of single (26g) intervention intake, given with high fat challenge | Insulin resistance, lipaemia, vascular, cognitive and lung function measured pre- and post-intervention in combination with a high fat challenge in a sub-group of participants. Urine samples and blood samples (over a 24 hour period) will be taken for biomarker analysis. | Chronic (0 to 6 month) |