Diet Intervention and GEnetic STudy (DIGEST-Pilot)

Sponsor

McMaster University (Other)

Overall Status

Unknown status

CT.gov ID

NCT01658137

Collaborator

(none)

Enrollment

Location

Arms

Duration (Months)

1.6

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Genetic factors contribute to risk factors for cardiovascular disease, such as blood lipids, blood pressure, obesity, diabetes, and may also influence dietary choices, physical activity, and responses to stress. The most robust genetic variant associated with myocardial infarction (MI) is the 9p21 variant, which may raise the risk of MI by up to 40% in those who carry 2 copies of the gene. The investigators recently found that among those who carry the 9p21 variant, the risk of MI may be "turned off" if individuals eat a diet high in fruits and vegetables. The investigators seek to determine how a "prudent" or "anti-inflammatory" diet interacts with the 9p21 risk allele to alter the risk of MI.

Condition or Disease	Intervention/Treatment	Phase
Cardiovascular Diseases Inflammation Dyslipidemias Blood Pressure Hyperglycemia	Other: Prudent Diet Other: Typical Western Diet	N/A

Detailed Description

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 Design

Study Type:

Interventional

Actual Enrollment :

84 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Prevention

Official Title:

Dietary Intervention Trial to Understand the Mechanism Underlying the 9p21 Variant Interaction With High Fruits and Vegetable Consumption

Study Start Date :

Jul 1, 2012

Anticipated Primary Completion Date :

Dec 1, 2016

Anticipated Study Completion Date :

Dec 1, 2016

Arms and Interventions

Arm	Intervention/Treatment
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).

Arm

Intervention/Treatment

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).

Outcome Measures

Primary Outcome Measures

gene expression measuring ANRIL production [baseline and 2 weeks]
epigenetic marks [baseline and 2 weeks]

Secondary Outcome Measures

high-sensitivity C-reactive protein [baseline and 2 weeks]
Biomarker of inflammation
interferon-alpha-21 [baseline and 2 weeks]
Biomarker of inflammation
interferon-gamma [baseline and 2 weeks]
Biomarker of inflammation
interleukin-1-alpha [baseline and 2 weeks]
Biomarker of inflammation
total cholesterol [baseline and 2 weeks]
lipid risk factor for cardiovascular disease
low-density lipoprotein-cholesterol [baseline and 2 weeks]
lipid risk factor for cardiovascular disease
high-density lipoprotein-cholesterol [baseline and 2 weeks]
lipid risk factor for cardiovascular disease
apolipoprotein-B [baseline and 2 weeks]
lipid risk factor for cardiovascular disease
fasting glucose [baseline and 2 weeks]
indicator of insulin resistance
systolic blood pressure [baseline and 2 weeks]
mmHg
diastolic blood pressure [baseline and 2 weeks]
mmHg
interleukin-6 [baseline and 2 weeks]
Biomarker of inflammation

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 80 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

Inclusion Criteria:

18-80 years old
non-smokers
Body-Mass-Index <=30 kg/m^2
willing and able to cook, prepare, and eat provided study foods

Exclusion Criteria:

Aged below 18 years or above 80 years
current tobacco smoking
Body mass index above 30 kg/m2
Unwillingness or inability to cook, prepare and eat provided study foods (e.g. for medical, philosophical, or religious reasons)
Excessive use of alcohol (>14 drinks/week in men; >7 drinks/week in women)
Significant morbidity that would interfere with participation or assessment, including :
Cancer
HIV
chronic renal disease
renal failure
Hepatitis/Jaundice
Liver Disease
Chronic Obstructive Pulmonary Disease
Inflammatory bowel disease (Crohn's / Colitis)
High blood or urine sugar/diabetes
High blood cholesterol or triglycerides
Angina/Heart attack/Coronary artery disease
Heart failure
Other heart disease
Angioplasty (balloon opening of an artery) or coronary bypass surgery
Medications or nutritional supplements (including multivitamins) that could affect outcome measurements. Excluded medications would include:
Lipid/cholesterol lowering pills
Insulin/oral hypoglycemic agents
Medication for stroke
Antibiotics
oral contraceptives
hormone replacement therapy
non-steroidal anti-inflammatory drugs
corticosteroids
unwillingness to stop nutritional supplements 1 week prior to and for duration of intervention
anticipated difficulties maintaining body weight (e.g. athletic training)