Enhanced Multicenter Dietary Portfolio Study — EDP8  

Cardiovascular Diseases Clinical Trial

Official title: The Effect of an Enhanced Dietary Portfolio Plus Exercise on Cardiovascular Risk in High Risk Individuals.

Status Withdrawn

Clinical Trial Summary

"Is it possible to recruit and retain up to 200 participants in a Randomize Control Trial (RCT) of high impact lifestyle approach of diet and exercise designed to significantly reduce cardiovascular events in middle-aged and older men and women at high risk of such events?" To address this question, we propose a pilot study of 3 years in duration: 1 year recruitment and randomization, a full year of intervention for all recruited participants, and the last 6 months to assess the one year data and prepare and submit the full trial application, informed by the pilot study outcomes in terms of retention rate. The pilot will then continue on for the full 9 years of intervention and be rolled into the main study involving additional Canadian centers and collaborating international centers in the US, Britain, Europe, Australia, New Zealand, India, and South Africa.

Clinical Trial Description

There is a major need for a large RCT to demonstrate the effect of lifestyle modification (diet and exercise) on cardiovascular disease (CVD) outcomes. The pilot study will demonstrate the feasibility as a prerequisite for continuing on to the large RCT. Large RCT: This trial will test the effect of a high impact dietary approach combining foods with functional effects, including LDL-cholesterol (LDL-C) and blood pressure (BP) reduction, together with an exercise program which has been associated with reduction in carotid atheroma assessed by MRI. The combined approach will have a more significant effect on CVD risk factors than previous trials and will be compared with a high cereal fibre diet and exercise advice, consistent with good clinical practice, in a randomized parallel trial of 9 years duration. ~6,000 high risk participants will be recruited comprising individuals with 1) type 2 diabetes, 2) post myocardial infarction (MI), and 3) Statin intolerant individuals. The primary outcome will be CVD event (MI, and stroke, fatal and non-fatal) (1). We believe we will achieve a 20% reduction in CVD events with ~10% related to diet reflected in reduction in traditional risk factors (LDL-C, BP) and 10% to exercise and increased cardiovascular fitness at year 9.

Pilot Study: We therefore propose to undertake a 1 year pilot study with 200 participants to demonstrate feasibility: 1) Successful recruitment (200 participants/year) and 2) retention (>90%)

Background: We have demonstrated the specific CVD reducing potential of the proposed components of our dietary intervention in a series of CIHR funded studies. The core dietary components (dietary portfolio of FDA approved cholesterol-lowering foods) in our recent CIHR-funded trial reduced LDL-C by 13-14% (JAMA 2011) with reductions also in diastolic blood pressure over 6 months. The CVD risk score was reduced by ~10% on the treatment. This approach will be combined with increased levels of monounsaturated fat (MUFA) which in a further CIHR-funded portfolio study raised HDL-C and reduced the total:HDL-C ratio (CMAJ 2010) resulting in an ~11% CVD risk score reduction on the high MUFA compared to the low MUFA portfolio. Low glycemic index foods will be selected which in our CIHR-funded trial in type 2 diabetes increased HDL-C and reduced HbA1c, the total:HDL-C ratio (JAMA 2008) and, with the added emphasis on legumes (dried peas, beans, lentils), significantly reduced BP leading to a CVD risk score reduction of ~5% (Arch Intern Med 2012). We consider this dietary package to have major potential in CVD risk reduction with a possible reduction in relative risk of 24% in the absence of negative or positive interactions.

The physical activity/exercise intervention is the end-product of a 25 year cumulative experience of investigators of the Quebec Heart and Lung Institute regarding physical activity/exercise prescriptions to various types of individuals/patients. Our program has also been recently tested in high risk patients with documented coronary artery disease managed by coronary artery bypass graft procedure (with/without type 2 diabetes). Unpublished preliminary results from this latter intervention in high risk patients indicate that our program not only induces substantial improvements in the CVD risk factor profile beyond clinical guidelines-aligned with optimal pharmacotherapy but that such an intervention appears to induce a significant reduction in carotid artery atherosclerosis assessed by magnetic resonance imaging. The latest meta-analysis estimated that only 150 min/week of moderate exercise reduced CHD risk by 14%. Our Laval program with a 420 min/wk of moderate exercise plus additional structured exercise would therefore also reduce CVD risk by at least 14% (or as much as 39% if the relationship between exercise time and CVD risk reduction were linear). The program aims to reduce sedentary behavior. It is safe and affordable in clinical practice. At a cost of about $900 per patient in the first year where the major training takes place, it is considerably less expensive than the DPP, DPS and Look AHEAD trials.

The research questions are therefore:

1. What is the feasibility in terms of recruitment and retention of implementing a high impact diet and physical activity/exercise program for CVD prevention in high risk or statin-intolerant individuals?

2. Based on the observed retention in the pilot study, the required recruitment for the large trial can be refined, if necessary. ;

Related Conditions & MeSH terms

• Cardiovascular Diseases
• Hypercholesterolemia
• Type 2 Diabetes

• NCT number: NCT01954472
• Study type: Interventional
• Source: St. Michael's Hospital, Toronto
• Status: Withdrawn
• Phase: N/A
• Completion date: October 7, 2014