Clinical trial NCT00462436: Innovative Strategies For Risk Reduction Following CABG
Official title: Do Innovative Strategies Complement Medical Management to Reduce Cardiovascular Risk Factors Following Coronary Artery Bypass Graft Surgery?
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Coronary Artery Disease
Type II Diabetes Mellitus
Keywords: functional foods
soy
nuts
LDL cholesterol
fibre
secondary prevention
risk reduction
endothelial function
endothelial progenitor cells
inflammation
glycemic control
HOMA
Lead sponsor: Unity Health Toronto
Sponsor class: OTHER
Collaborators: name: Canadian Diabetes Association
First posted: 2007-04-19
Enrollment: 35
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: PREVENTION

Brief summary: Background: Treatment targets for cardiac risk factor reduction are not being met. Therefore, there is a need for new strategies to assist patients in meeting these goals.

Objective: To determine the amount of any additional benefit on risk factor reduction associated with the consumption of the "dietary portfolio" (a low fat diet with soy, nuts and viscous fibres), above that achieved with medical management in diabetic patients following cardiac surgery.

Description: 35 cardiac surgery patients with diabetes will be instructed on how to incorporate the dietary portfolio foods into their diet for four weeks. Changes in blood cholesterol, markers of inflammation, blood sugar control and modifiable risk factors will be assessed after 2 and 4 weeks of therapy.

Relevance: Maximizing cardiac risk factor reduction through a combined approach (dietary plus medication) should improve outcomes, reduce rates of re-hospitalization and improve quality of life in diabetic patients after heart surgery.

Detailed description: Introduction: The consumption of a dietary portfolio has been found to successfully reduce LDL cholesterol by 30% in hyperlipidemic, non-diabetic patients under highly controlled conditions. Given the burden of cardiovascular disease in the diabetic population, it is now important that we evaluate whether consumption of the dietary portfolio can reduce modifiable risk factors and improve diabetic control above that associated with medical therapy alone in this population. The reduction of modifiable risk factors, particularly in the diabetic patient with coronary artery disease, should not only improve long-term outcomes thereby reducing re-admissions and subsequently the burden of the diabetic patient on the health care system, but also improve quality of life for these patients. This pilot project will determine the efficacy, feasibility and tolerability of an aggressive dietary strategy, the dietary portfolio of functional foods to reduce cardiovascular risk factors in diabetic patients following CABG.

Study Objectives: This study will determine to what extent the self selected "modified" dietary portfolio (without sterols) together with statin therapy will:

* reduce total and LDL cholesterol
* increase endothelial cell number and function and reduce CRP levels.
* reduce markers of inflammation and insulin resistance
* the study will also determine the tolerability of and compliance with the portfolio diet

Primary Hypothesis: The consumption of the modified dietary portfolio will have a pleiotropic effect with current statin therapy resulting in an additional reduction in LDL cholesterol of 25% after four weeks of treatment.

Secondary Hypotheses: The addition of the dietary portfolio together with statin therapy will:

* significantly increase measures of endothelial function and endothelial progenitor cell counts
* significantly reduce CRP levels
* be feasible and well tolerated by most bypass patients
* result in a compliance rate of 70% with the main components of the diet
* significantly improve the plasma total-C:HDL-C ratio, and total-C, HDL-C, apolipoproteins A-I and B levels after both two and four weeks of treatment
* significantly reduce markers of inflammation at four weeks (CRP, IL-6 and TNF)
* improve indices of glycemic control (HOMA), oxidized LDL and LDL particle size

Trial Design:

Subject Selection: Participants will be screened from those patients returning for their routine six week follow-up visit following their coronary artery bypass graft surgery. Eligible patients will be invited to participate in this secondary prevention trial by their surgeon. The six week time point for recruitment not only allows direct patient interaction but also ensures that sufficient time has passed for normalization of the lipid profile post CABG (20). Finally, at this time, most patients have also seen their cardiologist and have had their medication regimen adjusted following surgery, which should allow for a window of stable medical care over the course of the study.

Patients with type II diabetes are selected for this study as 1) this group of patients is at a higher risk of developing post-operative complications and therefore are most likely to receive the maximal benefit from risk factor modification, and 2) this group has increased cardiovascular risk and therefore should benefit on multiple levels by the addition of the portfolio diet including, but not limited to reduced LDL cholesterol, blood pressure, CRP and inflammatory response but also in improved insulin sensitivity and endothelial function. Finally since estrogen levels influence endothelial function, pre-menopausal women will be excluded from this pilot study.

Study Design: This is non-randomized pilot study investigating the magnitude of cardiovascular risk reduction achieved by the addition of a "modified portfolio diet" (DPF)(without plant sterols) consumed for one month under real life conditions in diabetic patients on statin therapy who have known cardiovascular disease. The four week intervention period has previously been found to be sufficient for significant changes in the primary outcome variable (LDL cholesterol) to occur but will be short enough to minimize the confounding effects of changes in medication and physical activity in hypercholesterolemic subjects not on statin therapy(21).

The study will involve one baseline and two follow-up visits (Figure 1). At baseline, demographic, anthropometric (weight, height, body mass index (BMI), waist/hip ratio) and medical/cardiac history will be obtained including a detailed list of current medications. Resting blood pressure will be measured (see analytic methods). Information regarding exercise and smoking habits will also be obtained at this time. Participants will receive comprehensive dietary advice by a trained registered dietitian at the Risk Factor Modification Centre. The DPF group will conform to current therapeutic diets appropriate for hypercholesterolemic subjects (\<7% of energy saturated fat, \<200 mg/d cholesterol) with the addition of a combination of viscous fibers, soy protein and almonds. Participants will be instructed on how to select and follow this diet and will be provided with samples of appropriate foods to assist in the initial selection of and compliance with the DPF. All participants will receive a weekly allowance for the purchase of appropriate foods. The portfolio diet plan will include foods which contribute 8 g/1000 kcal viscous fiber as β-glucan (oats, barley, oat bran breads and soups) and psyllium (cereal), 17 g soy protein/1000 kcal (soy burgers, hot dogs, links, other meat analogues, milks, yogurts and cheese) and 22 g nuts (almonds)/1000 kcal. Participants at the Risk Factor Modification Centre have been maintained on this level of fiber intake for 4-month periods (22). Moderate weight loss (0.5kg/week) for those with a BMI \>25 and routine physical activity using the guidelines from the Guide to Cardiac surgery will be encouraged as part of this secondary prevention strategy. During the baseline visit, the coordinator (MSc student) will complete a 24 hour dietary recall to obtain an idea of estimated dietary intake. This recall together with calculated energy requirements using established equations will be used to assess individual energy intake. Using this estimate, the coordinator will advise the participant on how to incorporate the DPF into their eating patterns. The coordinator will instruct patients on detailed diet history recording, and each participant will be provided printed booklets in which to record the food items and their approximate size. Since determining compliance is an important end-point, self-taring scales will be provided to assist with accuracy. Subjects will be asked to complete daily a checklist of their consumption of the three key foods or food components of the portfolio diet (23,24). Assessment of the checklists for the three key dietary components will provide not only an estimate of compliance but will also assist patients in monitoring on a daily basis how many foods from the portfolio they have consumed. The coordinator will complete 4 random 24 hour recalls with each study subject, using standardized techniques, throughout the study period in order to validate the compliance checklist data. Recall data will be analyzed using a program based on USDA data (25) with additional data on foods analyzed in the laboratory for protein, total fat, and dietary fiber using the methods of the Association of Official Analytical Chemists (AOAC) (26) as well as the tables of Anderson and Bridges (27).

Since the DPF is part of a comprehensive secondary prevention strategy, all participants will be encouraged to follow the guidelines for physical activity (30 minutes, 3-5 times per week) outlined in the Guide for Cardiac Surgery Outpatient Handbook. The amount of physical activity will be recorded using a pedometer and will be recorded at the bottom of their food checklist. Fasting blood samples will be collected for primary and secondary markers of cardiovascular risk, insulin resistance and endothelial function. Brachial artery vasoreactivity will be completed at the same time of day with each participant under fasting conditions. Medications will be held the morning of the test.

Significance of Proposal: This study will determine the magnitude of any additional cardiovascular risk reduction associated with the consumption of the "modified dietary portfolio" in diabetic patients with coronary artery disease on statin therapy. Furthermore, since the dietary portfolio is an aggressive strategy, this study will also determine the feasibility and tolerability of this type of intervention in patients living in the community. Finally, this study may justify a larger secondary prevention trial looking at the effect of this intervention on cardiac outcomes and rates of re-hospitalization following bypass grafting. Aggressive, innovative, patient driven dietary strategies may complement medical management improving the ability of patients to meet treatment targets ultimately resulting in improved patient outcomes and quality of life following bypass graft surgery.

Eligibility criteria: Inclusion Criteria:

1. Patients with type II diabetes mellitus
2. Recently (\<5 months) undergone coronary artery bypass graft surgery
3. Taking cholesterol lowering medication

Exclusion Criteria:

1. Can not speak English and have no available interpreter
2. Refuse Informed Consent
3. Had "off pump" CABG
4. Are intolerant of statins
5. Are pre-menopausal (women) or are on HRT
6. Have serious concomitant disease
7. Take insulin
8. Are \<18 years of age
9. receive incomplete revascularization
10. documented history of drug or alcohol abuse
11. Intend to become pregnant during study period
12. Have an unreliable psychological condition that makes them unlikely to comply

Primary outcomes:
measure: Primary Outcome: Reduction of total and LDL cholesterol
timeFrame: baseline to 4 weeks
Secondary outcomes:
measure: Improvement in endothelial function and EPC counts
timeFrame: Baseline to 4 weeks
measure: Reduction in CRP
timeFrame: baseline to 4 weeks
measure: Feasibility and tolerability
timeFrame: Baseline to 4 Weeks
measure: Reduction in markers of inflammation ie TNF, IL-6
timeFrame: Baseline to 4 weeks
measure: Improved markers of glycemic control - fructosamine, HOMA
timeFrame: baseline to 4 weeks
Other outcomes:
Locations:
city: Toronto
country: Canada
facility: St. Michael's Hospital
state: Ontario
Study officials:
affiliation: Unity Health Toronto
name: Mary Keith, PhD, RD
role: PRINCIPAL_INVESTIGATOR
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