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

March 4, 2024 updated by: Ole Frobert, MD, PhD

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

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.

Study Overview

Study Type

Interventional

Enrollment (Estimated)

900

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

      • Aarhus, Denmark
        • Not yet recruiting
        • Steno Diabetes center
        • Contact:
          • Sören Gregersen, Prof
      • Odense, Denmark
        • Recruiting
        • Odense University Hospital
        • Contact:
          • Mona El Faramawi, MD
      • Falun, Sweden
        • Not yet recruiting
        • Falu Lasarett
        • Contact:
          • Kristina Hambreaus, MD
      • Gothenburg, Sweden
        • Recruiting
        • Sahlgrenska Universitetssjukhuset
        • Contact:
          • Carlo Pirazzi, MD, PhD
      • Karlstad, Sweden
        • Recruiting
        • Karlstad general hospital
        • Contact:
          • Payam Khalili, MD, PhD
      • Lund, Sweden, 221 00
        • Recruiting
        • Department of Cardiology, Skånes universitetssjukhus
        • Contact:
      • Västerås, Sweden, 721 89
        • Recruiting
        • Cardiology Clinic, Västmanlands sjukhus
        • Contact:
      • Örebro, Sweden, 701 85

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Bilberry
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.
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 Comparator: Reference/Placebo
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.
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.
Experimental: Bioprocessed oat bran
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.
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.
Experimental: Combination of oat and bilberry
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.
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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Plasma levels of LDL cholesterol
Time Frame: Three months
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
Time Frame: Three months
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
Time Frame: Three months
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
Time Frame: Three months
The effect of intervention on muscle endurance
Three months
Self-reported physical activity level
Time Frame: Three months
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
Time Frame: Three months
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
Time Frame: Three months
The effect if intervention on plasma concentrations of biochemical markers of insulin, creatinine, Cystatin C, glucose and C-peptide
Three months
Untargeted plasma metabolome
Time Frame: Three months
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
Time Frame: Three months
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
Time Frame: Three months
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
Time Frame: Three months
The effect of intervention on resting heart rate
Three months
Systolic and diastolic blood pressure
Time Frame: Three months
The effect of intervention on blood pressure (mmHg)
Three months
Urine albumin-creatinine ratio
Time Frame: Three months
Urine albumin-creatinine ratio will be measured for for T2DM only
Three months
Continuous glucose monitoring
Time Frame: Three months
Continuous glucose monitoring (in a subset of T2DM only, n=80 in total)
Three months
Body composition with multi-frequency biothesiometry
Time Frame: Three months
Body composition willbe measured with multi-frequency biothesiometry (for T2DM only)
Three months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Investigators

  • Study Director: Ole Frobert, Prof, Department of Cardiology, Örebro Univerity Hospital, 701 85 Örebro, Sweden
  • Principal Investigator: Cecilia Bergh, PhD, Clinical Epidemiology and Biostatistics, School of medical Sciences, örebro University, Sweden

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

September 30, 2021

Primary Completion (Estimated)

December 31, 2025

Study Completion (Estimated)

December 31, 2025

Study Registration Dates

First Submitted

August 2, 2018

First Submitted That Met QC Criteria

August 2, 2018

First Posted (Actual)

August 8, 2018

Study Record Updates

Last Update Posted (Estimated)

March 6, 2024

Last Update Submitted That Met QC Criteria

March 4, 2024

Last Verified

March 1, 2024

More Information

Terms related to this study

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Myocardial Infarction

Clinical Trials on Bilberry

3
Subscribe