Diet Intervention and GEnetic STudy (DIGEST-Pilot) (DIGEST)
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|ClinicalTrials.gov Identifier: NCT01658137|
Recruitment Status : Unknown
Verified June 2016 by Sonia Anand, McMaster University.
Recruitment status was: Active, not recruiting
First Posted : August 6, 2012
Last Update Posted : June 7, 2016
|Condition or disease||Intervention/treatment||Phase|
|Cardiovascular Diseases Inflammation Dyslipidemias Blood Pressure Hyperglycemia||Other: Prudent Diet Other: Typical Western Diet||Not Applicable|
Cardiovascular disease (CVD) is the leading cause of death globally. The majority of CVD is explained by conventional risk factors including cigarette smoking, abnormal lipids, high blood pressure, obesity, diabetes, and health behaviours including dietary intake, physical activity, and psychosocial stressors. Genetic factors contribute to the development of these risk factors, and directly to CVD through other novel pathways. Since the advent of high throughput chip-based genotyping, more than 30 genetic variants have been found to be associated with myocardial infarction. The most robust genetic variant which has been consistently associated with myocardial infarction and other forms of arterial disease is the 9p21 variant. This genetic variant located on Chromosome 9 is common in the population, with 50% of people carrying one copy of the risk allele, and an additional 25% of the population carrying two copies of the risk allele. Compared with those with no copies of the risk allele, the risk of myocardial infarction with one copy of the risk allele is 15-20% higher, and the increased risk among carriers of 2 risk alleles is 20-40%. To date the exact mechanism by which the 9p21 variant increases the risk of myocardial infarction is unknown, although some data suggests that other genes and pathways associated with cell proliferation and inflammation are involved. Recently we made the observation that among carriers of the 9p21 variant, the risk of MI may be "turned off" if individuals consumed a diet high in fruits and vegetables. However the "mechanism" underlying this interaction is unknown. We seek to discover how a "Prudent" (i.e. anti-inflammatory) diet interacts with the 9p21 risk allele(s) to alter the risk of myocardial infarction.
We postulate that a "Prudent" diet (i.e. a diet high in fruits, vegetables, whole grains, non-processed foods) in comparison to a "Western" or "inflammatory diet" (eg, a typical North American diet high in saturated fats and processed foods) will differentially alter the gene expression (measured by RNA) of the 9p21 locus, change the epigenetic marks in this region, and alter several inflammatory markers suspected to mediate the effect of 9p21 on CVD risk (eg, hs-CRP, IF-alpha21, IFN-γ , interleukin 1-alpha, interleukin 1-beta, and interleukin 6) among people with one or two copies of the risk allele compared to people without the risk allele.
The proposed study offers an unique approach to studying dietary relationships with endpoints believed to be influenced by 9p21 gene variants. Rather than testing nutritional supplements, our results will be generalizable to the setting of most dietary counseling practices, which aim to alter dietary patterns, not specific nutrients. This trial will help us to unravel the basis for gene-diet interactions and gain a greater understanding of how inflammation is linked to the development of atherosclerosis, CVD, and possibly some cancers.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||84 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||None (Open Label)|
|Official Title:||Dietary Intervention Trial to Understand the Mechanism Underlying the 9p21 Variant Interaction With High Fruits and Vegetable Consumption|
|Study Start Date :||July 2012|
|Estimated Primary Completion Date :||December 2016|
|Estimated Study Completion Date :||December 2016|
Active Comparator: Typical Western Diet
The comparator dietary pattern ("Typical Western Diet") approximates the inflammatory dietary pattern typically consumed by North Americans. It contains refined grains, processed foods, dairy fat, meats, sugar and high glycemic index foods, and few fruits, nuts, legumes, and vegetables. The fruits and vegetables are highly processed (e.g. juices) and lower in micronutrients than those in the intervention diet. The saturated fat content of this diet does not meet national guidelines for health. The polyunsaturated fat:saturated fat ratio is ~0.5 (low).
Other: Typical Western Diet
This intervention lasts 2 weeks (14 days).
Experimental: Prudent Diet
The experimental dietary pattern ("Prudent Diet") is based on intakes of foods hypothesized to have beneficial effects on inflammation and long-term health. This dietary pattern includes micronutrient and macronutrient levels consistent with healthy eating in epidemiological studies and randomized controlled trials. The diet is constructed with low-fat dairy products, fish, chicken, and lean meats to minimize saturated fat and increase protein and calcium. The diet is rich in fruits, vegetables, whole grains, nuts, legumes, and seeds that are good sources of potassium, magnesium, and dietary fiber. This diet provides a 'favorable' macronutrient profile that is low in saturated fat, has a polyunsaturated/saturated fat ratio of ~1.0 (high), and low in high glycemic index carbohydrates.
Other: Prudent Diet
This intervention lasts 2 weeks (14 days).
- gene expression measuring ANRIL production [ Time Frame: baseline and 2 weeks ]
- epigenetic marks [ Time Frame: baseline and 2 weeks ]
- high-sensitivity C-reactive protein [ Time Frame: baseline and 2 weeks ]Biomarker of inflammation
- interferon-alpha-21 [ Time Frame: baseline and 2 weeks ]Biomarker of inflammation
- interferon-gamma [ Time Frame: baseline and 2 weeks ]Biomarker of inflammation
- interleukin-1-alpha [ Time Frame: baseline and 2 weeks ]Biomarker of inflammation
- total cholesterol [ Time Frame: baseline and 2 weeks ]lipid risk factor for cardiovascular disease
- low-density lipoprotein-cholesterol [ Time Frame: baseline and 2 weeks ]lipid risk factor for cardiovascular disease
- high-density lipoprotein-cholesterol [ Time Frame: baseline and 2 weeks ]lipid risk factor for cardiovascular disease
- apolipoprotein-B [ Time Frame: baseline and 2 weeks ]lipid risk factor for cardiovascular disease
- fasting glucose [ Time Frame: baseline and 2 weeks ]indicator of insulin resistance
- systolic blood pressure [ Time Frame: baseline and 2 weeks ]mmHg
- diastolic blood pressure [ Time Frame: baseline and 2 weeks ]mmHg
- interleukin-6 [ Time Frame: baseline and 2 weeks ]Biomarker of inflammation
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01658137
|Hamilton, Ontario, Canada, L8S 4K1|
|Principal Investigator:||Sonia S Anand, MD, PhD||McMaster University; Hamilton Health Sciences Center; Population Health Research Institute|