Effects of Dietary Flaxseed on Symptoms of Cardiovascular Disease in Patients With Peripheral Arterial Disease (FLAXPAD)

A Double Blind, Randomized, Placebo Controlled, Study for Assessment of Dietary Flaxseed on Improving Symptoms of Cardiovascular Disease in Patients With Peripheral Arterial Disease

This Clinical Trial is being conducted to study how patients with peripheral arterial disease (a condition in which the blood vessels of the extremities are affected) respond to a dietary regimen of flaxseed. The purpose of the study is to examine whether or not dietary flaxseed have any effect on improving symptoms of cardiovascular disease. Additionally, the effects of dietary flaxseed on exercise tolerance will be assessed.

Study Overview

• Status: Completed
• Conditions: Peripheral Arterial Disease
• Intervention / Treatment: Dietary supplement: Placebo; Dietary supplement: Flaxseed

Detailed Description

The proposed trial is a one year, double blinded, placebo controlled study designed to examine and compare the effects of dietary ground flaxseed supplementation in volunteers with claudication secondary to lower extremity atherosclerotic arterial disease (peripheral arterial disease). The original proposal was for a two year study duration but this was truncated at one year to insure patient compliance remained high. This patient population is likely to benefit from flaxseed because there is a high prevalence of accelerated atherosclerosis and a higher than normal incidence of arrhythmias, myocardial infarctions and stroke. This study will be focus on whether dietary flaxseed can reduce clinical manifestations of peripheral arterial disease and increase exercise capacity in these patients. Two general hypotheses will be tested in this proposal. First, we hypothesize that fewer primary and secondary events (all-cause mortality, cardiovascular mortality, stroke, myocardial infarctions, angina, arrhythmias) will occur in patients who ingest flaxseed in their diet. Secondly, we hypothesize that dietary flaxseed supplementation will be associated with beneficial effects on exercise performance, blood pressure and circulating lipid levels. This trial will generate data on the safety, tolerability, cardiovascular efficacy and genomic response to a diet rich in flaxseed in patients with peripheral arterial disease (PAD).

• Study Type: Interventional
• Enrollment (Actual): 110
• Phase: Phase 2; Phase 3

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years to 100 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Subjects with peripheral arterial disease for more than 6 months.
• Male or female with claudication secondary to lower extremity atherosclerotic arterial disease. (with limited IC but not incapacitated for walking on the level) confirmed with ankle/brachial pressures< or = to 0.9 in one or both legs) or who have had a previous intervention for peripheral arterial disease.
• Over 40 years old
• Able to comply with protocol requirements
• Able to provide informed consent
• Subjects taking anti-platelet therapy medication must be on a stable dose for 3 months prior to as well as during the study.
• Subjects taking lipid lowering medication must be on a stable dose for 3 months prior to as well as during the study.

Exclusion Criteria:

• Patients with ischemic rest pain in limbs, ulceration, or gangrene.
• At baseline, any condition that prevents walking on a treadmill.
• History of major bleeding.
• Patients with bowel disease (including Crohn's disease, celiac disease, peptic ulcer disease, irritable bowel syndrome and diverticulosis).
• Patients with an estimated life expectancy less than 2 years and with high baseline cardiac risk (post ischemic or diabetic cardiomyopathy with EF<40%, Canadian Cardiovascular Society Class 3 or 4 angina or need for coronary revascularization procedures).
• Moderate to severe renal failure.
• Subjects that are on supplements other that those prescribed by their clinician for the entire duration of the study.
• Fish limitations (no more than 2 fish meals per week)
• Gluten allergy
• Subjects with allergies to any ingredient in the study product or placebo.
• Patients who plan to undergo surgery during the course of the trial.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; Randomized, Blinded Controlled Arm of patients receiving placebo food products (ie: bagels, muffins, bars, pasta, buns, and milled seeds) containing a mixture of wheat and wheat bran to replace the flaxseed daily for one year.	Dietary supplement: Placebo; Wheat and Mixed Dietary Oils
Experimental: Flaxseed; Randomized, Blinded group of patients that will be given food products (ie: bagels, muffins, bars, pasta, buns, and milled seeds) containing 30 g of milled flaxseed daily for one year	Dietary supplement: Flaxseed; 30 grams of milled flaxseed per day in food products or on its own.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Number of Participants With All-cause Mortality, Cardiovascular Mortality, Stroke, and Myocardial Infarctions	1 year

Secondary Outcome Measures

Outcome Measure	Time Frame
Effects on Exercise Performance, Blood Pressure and Circulating Lipid Levels.	1 year

Collaborators and Investigators

• Sponsor: Dr. Grant Pierce
• Investigators: Principal Investigator: Grant Pierce, PhD, University of Manitoba

Publications and helpful links

General Publications

• Caligiuri SP, Rodriguez-Leyva D, Aukema HM, Ravandi A, Weighell W, Guzman R, Pierce GN. Dietary Flaxseed Reduces Central Aortic Blood Pressure Without Cardiac Involvement but Through Changes in Plasma Oxylipins. Hypertension. 2016 Oct;68(4):1031-8. doi: 10.1161/HYPERTENSIONAHA.116.07834. Epub 2016 Aug 15.
• Edel AL, Rodriguez-Leyva D, Maddaford TG, Caligiuri SP, Austria JA, Weighell W, Guzman R, Aliani M, Pierce GN. Dietary flaxseed independently lowers circulating cholesterol and lowers it beyond the effects of cholesterol-lowering medications alone in patients with peripheral artery disease. J Nutr. 2015 Apr;145(4):749-57. doi: 10.3945/jn.114.204594. Epub 2015 Feb 18.
• Caligiuri SP, Aukema HM, Ravandi A, Guzman R, Dibrov E, Pierce GN. Flaxseed consumption reduces blood pressure in patients with hypertension by altering circulating oxylipins via an alpha-linolenic acid-induced inhibition of soluble epoxide hydrolase. Hypertension. 2014 Jul;64(1):53-9. doi: 10.1161/HYPERTENSIONAHA.114.03179. Epub 2014 Apr 28.

Helpful Links

• Canadian Centre for Agri-food Research in Health and Medicine

Study record dates

Study Major Dates

• Study Start: October 1, 2008
• Primary Completion (Actual): March 1, 2011
• Study Completion (Actual): October 1, 2016

Study Registration Dates

• First Submitted: October 28, 2008
• First Submitted That Met QC Criteria: October 28, 2008
• First Posted (Estimate): October 29, 2008

Study Record Updates

• Last Update Posted (Estimate): December 12, 2016
• Last Update Submitted That Met QC Criteria: October 27, 2016
• Last Verified: October 1, 2016

More Information

Terms related to this study

• Keywords: Diabetes; PAD; Atherosclerosis; Peripheral Arterial Disease; Functional Foods; Flax; Flaxseeds; Essential Fatty Acids; Winnipeg
• Additional Relevant MeSH Terms: Vascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Atherosclerosis; Cardiovascular Diseases; Peripheral Arterial Disease; Peripheral Vascular Diseases
• Other Study ID Numbers: 10941-011