Effects of Bilberry and Oat Intake After Type 2 Diabetes and/or MI

Myocardial Infarction Clinical Trial

— BioDiaMI  

Official title:

Effects of Bilberry and Oat Intake on Plasma Lipid Profile, Inflammation, and Exercise Capacity in Patients With Type 2 Diabetes and/or Myocardial Infarction (BioDiaMI): a Randomized, Double-blind, Placebo-controlled Trial

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03620266
• Other study ID #: BioDiaMI
• Status: Recruiting
• Phase: N/A
• Start date: September 30, 2021
• Est. completion date: December 31, 2025

Study information

• Verified date: April 2024
• Source: Region Örebro County
• Contact: Ole Frobert, Prof
• Phone: +46 19 602 543
• Email: ole.frobert[@]regionorebrolan.se
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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 for patients with manifest chronic cardiometabolic disease, such as type 2 diabets mellitus (T2DM) and myocardial infarction (MI). However, 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, for patients diagnosed with T2DM and/or MI. 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, glycaemia, and gut microbiota composition after three months.

Implications:

Secondary prevention after cardiometabolic disease, including T2DM and MI, has improved during the last decades but diabetes complications, readmissions and cadiovascular related deaths following these conditions remain large health care challenges. Controlling hyperlipidemia, hyperglycaemia, hypertension 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 in high-risk patients or risk prevention in subjects with T2DM.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 900
• Est. completion date: December 31, 2025
• Est. primary completion date: December 31, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion criteria

• Confirmed T2DM diagnosis (any treatment modality accepted) and/or within 3 years post STEMI or NSTEMI

• Completed coronary angiography/PCI

• Male and female subjects =18 years

• Allocated to atorvastatin at a daily dose of 80 mg (only eligible for patients enrolled up to 7 days post MI and not for T2D subjects)

• 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 BioDiaMI trial

• Inability to provide informed consent

Related Conditions & MeSH terms

• Diabetes Mellitus, Type 2
• Infarction
• Myocardial Infarction

Intervention

Dietary Supplement:
• Bilberry
The dietary intervention will 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.
• Placebo
The dietary intervention 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.
• Bioprocessed oat bran
The dietary intervention 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.
• Combination bilberry/oats
The dietary intervention 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.

Locations

Country	Name	City	State
Denmark	Steno Diabetes center	Aarhus
Denmark	Odense University Hospital	Odense
Sweden	Falu lasarett	Falun
Sweden	Sahlgrenska Universitetssjukhuset	Gothenburg
Sweden	Karlstad general hospital	Karlstad
Sweden	Department of Cardiology, Skånes universitetssjukhus	Lund
Sweden	Department of Cardiology, Örebro University Hospital	Örebro
Sweden	Cardiology Clinic, Västmanlands sjukhus	Västerås

Sponsors (9)

Lead Sponsor	Collaborator
Ole Frobert, MD, PhD	Aarhus University Hospital, Chalmers University of Technology, Falu Hospital, Odense University Hospital, Region Skane, Region Västmanland, Värmland County Council, Sweden, Vastra Gotaland Region

Countries where clinical trial is conducted

Denmark,  Sweden, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Plasma levels of LDL cholesterol	The effect of intervention on difference between the groups of LDL cholesterol after three months	Three months
Secondary	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
Secondary	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
Secondary	Dynamic unilateral heel-lft and unilateral shoulder flexion tests	The effect of intervention on muscle endurance	Three months
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	Resting heart rate	The effect of intervention on resting heart rate	Three months
Secondary	Systolic and diastolic blood pressure	The effect of intervention on blood pressure (mmHg)	Three months
Secondary	Urine albumin-creatinine ratio	Urine albumin-creatinine ratio will be measured for for T2DM only	Three months
Secondary	Continuous glucose monitoring with Continuous Glucose Monitors (CGM) - FreeStyle model 2	Continuous glucose monitoring (in a subset of T2DM only, n=80 in total)	Three months
Secondary	Body composition with multi-frequency biothesiometry	Body composition willbe measured with multi-frequency biothesiometry (for T2DM only)	Three months