Effects of Bilberry and Oat Intake After AMI

Study Overview
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Brief Summary
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Background: Bilberries from Sweden, rich in polyphenols, have shown cholesterol-lowering effects in small studies, and the cholesterol-lowering properties of oats, with abundant beta-glucans and potentially bioactive phytochemicals, are well established. Both may provide cardiometabolic benefits following acute myocardial infarction (AMI), but large studies of adequate statistical power and appropriate duration are needed to confirm clinically relevant treatment effects. No previous study has evaluated the potential additive or synergistic effects of bilberry combined with oats on cardiometabolic risk factors. Design: This is a double-blind, randomized, placebo-controlled clinical trial. Our primary objective is to assess cardioprotective effects of diet supplementation with dried bilberry and with bioprocessed oat bran, with a secondary explorative objective of assessing their combination, compared with a neutral isocaloric reference supplement, initiated within five days following percutaneous coronary intervention for AMI. Patients will be randomized 1:1:1:1 to a three-month intervention. The primary endpoint is the difference in LDL cholesterol change between the intervention groups after three months. The major secondary endpoint is exercise capacity at three months. Other secondary endpoints include plasma concentrations of biochemical markers of inflammation, metabolomics and gut microbiota composition after three months. Implications: Secondary prevention after AMI has improved during the last decades but readmissions and death following AMI remain large health care challenges. Controlling hyperlipidemia and inflammation is critical to preventing new cardiovascular events, but novel pharmacological treatments for these conditions are expensive and associated with negative side effects. If bilberry and/or oat, in addition to standard medical therapy, can lower LDL cholesterol and inflammation more than standard therapy alone, this could be a cost-effective and safe dietary strategy for secondary prevention after AMI.

Official Title
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Effects of Bilberry and Oat Intake on Lipids, Inflammation, and Exercise Capacity After Acute Myocardial Infarction (BIOAMI): a Randomized, Double-blind, Placebo-controlled Trial

Conditions
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Myocardial Infarction

Intervention / Treatment
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* Dietary Supplement: Bilberry
* Dietary Supplement: Placebo
* Dietary Supplement: Bioprocessed oat bran
* Dietary Supplement: Combination bilberry/oats


Participation Criteria
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Eligibility Criteria
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Inclusion criteria STEMI or NSTEMI Completed coronary angiography/PCI Male and female subjects ≥18 years Allocated to atorvastatin at a daily dose of 80 mg Written informed consent Exclusion criteria Emergency coronary artery bypass grafting <18 years of age LDL cholesterol <2.0 mmol/L Daily intake or the intent to initiate daily intake of bilberry in any form or daily intake of >15 g of oatmeal or equivalent Food allergy/intolerance to gluten, bilberries or legumes Previous randomization in the BIOAMI trial Inability to provide informed consent

Ages Eligible for Study
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Minimum Age: 18 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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Bilberry<br>Dietary supplement with bilberry shakes 2 times daily for 3 months (containing in total 40g of dried bilberry powder equalling 480 g of fresh berries per day). Product development in collaboration with Glucanova AB. | Dietary Supplement: Bilberry<br>* The dietary intervention will be initiated within five days post PCI and will be continued for three months. After randomization, participants will be given bilberry shakes (active), liquid oat shakes (active), a combination shake with bilberry and oats, or reference shakes (placebo product containing no active bilberry or active oats but with similar taste and texture as both oat and bilberry), for intake two times a day (t.i.d). The formula for the shakes to be used in the intervention will be finalized during the initial project period.<br>|
| Placebo Comparator: Reference/Placebo<br>Dietary supplement with reference shakes 2 times daily for 3 months (containing no active bilberry or no active oats, but with similar texture and taste as both bilberry and oat). Product development in collaboration with Glucanova AB. | Dietary Supplement: Placebo<br>* The dietary intervention will be initiated within five days post PCI and will be continued for three months. After randomization, participants will be given bilberry shakes (active), liquid oat shakes (active), a combination shake with bilberry and oats, or reference shakes (placebo product containing no active bilberry or active oats but with similar taste and texture), for intake two times a day (t.i.d). The formula for the shakes to be used in the intervention will be finalized during the initial project period.<br>|
| Experimental: Bioprocessed oat bran<br>Dietary supplement with bioprocessed oat bran shakes 2 times daily for 3 months (containing beta glucans from the Glucanova® technology, invented by Glucanova AB).Product development in collaboration with Glucanova AB. | Dietary Supplement: Bioprocessed oat bran<br>* The dietary intervention will be initiated within five days post PCI and will be continued for three months. After randomization, participants will be given bilberry shakes (active), liquid oat shakes (active), a combination shake with bilberry and oats, or reference shakes (placebo product containing no active bilberry or active oats but with similar taste and texture), for intake two times a day (t.i.d). The formula for the shakes to be used in the intervention will be finalized during the initial project period.<br>|
| Experimental: Combination of oat and bilberry<br>Dietary supplement with a combination of bioprocessed oat bran and dried bilberry (shakes) 2 times daily for 3 months. Product development in collaboration with Glucanova AB. | Dietary Supplement: Combination bilberry/oats<br>* The dietary intervention will be initiated within five days post PCI and will be continued for three months. After randomization, participants will be given bilberry shakes (active), liquid oat shakes (active), a combination shake with bilberry and oats, or reference shakes (placebo product containing no active bilberry or active oats but with similar taste and texture), for intake two times a day (t.i.d). The formula for the shakes to be used in the intervention will be finalized during the initial project period.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Plasma levels of LDL cholesterol | The effect of intervention on difference between the groups of LDL cholesterol after three months | Three months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Plasma lipid profile | The effect of intervention on differences between the groups of fasting lipid profile including HDL, triglycerides, total cholesterol, small-dense LDL cholesterol, apo A, apo B, Lp(a) and oxidized LDL. | Three months | 
| Symptom-limited bicycle ergometer test | The effect of intervention on exercise capacity (measured as maximal workload in Watts and as estimated maximal oxygen uptake (VO2 max)) | Three months | 
| Dynamic unilateral heel-lft and unilateral shoulder flexion tests | The effect of intervention on muscle endurance | Three months | 
| Self-reported physical activity level | The effect of intervention on the Frändin/Grimby activity scale (6 levels of physical activity, min:1 (low activity) max:6 (heavy activity)) and the Haskell physical activity scale (For how many days were you physically active during the last week for at least 20 minutes?, min:0 max:7) | Three months | 
| Plasma concentrations of inflammatory and heart function markers | The effect of intervention on plasma concentrations of biochemical markers of troponin, NT-proBNP, hs_CRP (high sensitivity C-reactive protein), IL-6 and HbA1c (glycosylated hemoglobin). | Three months | 
| Plasma concentrations of other biochemical markers | The effect if intervention on plasma concentrations of biochemical markers of insulin, creatinine, Cystatin C, glucose and C-peptide | Three months | 
| Untargeted plasma metabolome | Untargeted plasma metabolomics will be employed to exploratively assess alterations in endogenous and exposome-related metabolites and to identify metabolites that may differ with treatment. | Three months | 
| Fecal samples of gut microbiota composition | These exploratory analyses of will allow to investigate the extent to which gut microbiota composition and activity differs between responders and non-responders to the interventions. | Three months | 
| Left ventricular systolic function | The effect of intervention on left ventricular function. Baseline left ventricular systolic function, expressed as global ejection fraction in percent according to the biplane Simpson method, will be evaluated by echocardiography by the discharging physician. The procedure will be repeated after three months by an experienced echocardiography technician blinded to results of the initial examinations | Three months | 
| Resting heart rate | The effect of intervention on resting heart rate | Three months | 
| Systolic and diastolic blood pressure | The effect of intervention on blood pressure (mmHg) | Three months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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acute myocardial infarction, diet therapy, anthocyanin, bilberry bush, exercise capacity, cholesterol, beta glucans