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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
Information provided by (Responsible Party):
Sonia Anand, McMaster University

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 Not Applicable

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.

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Study Type : Interventional  (Clinical Trial)
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 : July 2012
Estimated Primary Completion Date : December 2016
Estimated Study Completion Date : December 2016

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).

Primary Outcome Measures :
  1. gene expression measuring ANRIL production [ Time Frame: baseline and 2 weeks ]
  2. epigenetic marks [ Time Frame: baseline and 2 weeks ]

Secondary Outcome Measures :
  1. high-sensitivity C-reactive protein [ Time Frame: baseline and 2 weeks ]
    Biomarker of inflammation

  2. interferon-alpha-21 [ Time Frame: baseline and 2 weeks ]
    Biomarker of inflammation

  3. interferon-gamma [ Time Frame: baseline and 2 weeks ]
    Biomarker of inflammation

  4. interleukin-1-alpha [ Time Frame: baseline and 2 weeks ]
    Biomarker of inflammation

  5. total cholesterol [ Time Frame: baseline and 2 weeks ]
    lipid risk factor for cardiovascular disease

  6. low-density lipoprotein-cholesterol [ Time Frame: baseline and 2 weeks ]
    lipid risk factor for cardiovascular disease

  7. high-density lipoprotein-cholesterol [ Time Frame: baseline and 2 weeks ]
    lipid risk factor for cardiovascular disease

  8. apolipoprotein-B [ Time Frame: baseline and 2 weeks ]
    lipid risk factor for cardiovascular disease

  9. fasting glucose [ Time Frame: baseline and 2 weeks ]
    indicator of insulin resistance

  10. systolic blood pressure [ Time Frame: baseline and 2 weeks ]

  11. diastolic blood pressure [ Time Frame: baseline and 2 weeks ]

  12. interleukin-6 [ Time Frame: baseline and 2 weeks ]
    Biomarker of inflammation

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 80 Years   (Adult, Older Adult)
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)

Information from the National Library of Medicine

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

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Canada, Ontario
McMaster University
Hamilton, Ontario, Canada, L8S 4K1
Sponsors and Collaborators
McMaster University
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Principal Investigator: Sonia S Anand, MD, PhD McMaster University; Hamilton Health Sciences Center; Population Health Research Institute

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Responsible Party: Sonia Anand, Professor, McMaster University
ClinicalTrials.gov Identifier: NCT01658137    
Other Study ID Numbers: DIGEST-Pilot
First Posted: August 6, 2012    Key Record Dates
Last Update Posted: June 7, 2016
Last Verified: June 2016
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Plan Description: Because sensitive genetic material was collected as part of this pilot study, data from this study will not be shared.
Keywords provided by Sonia Anand, McMaster University:
dietary pattern
gene expression
diet-gene interaction
Additional relevant MeSH terms:
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Cardiovascular Diseases
Pathologic Processes
Lipid Metabolism Disorders
Metabolic Diseases
Glucose Metabolism Disorders