Diet Intervention and GEnetic STudy (DIGEST-Pilot)

The recruitment status of this study is unknown because the information has not been verified recently.
Verified August 2012 by McMaster University.
Recruitment status was  Recruiting
Sponsor:
Information provided by (Responsible Party):
Sonia Anand, McMaster University
ClinicalTrials.gov Identifier:
NCT01658137
First received: July 28, 2012
Last updated: August 1, 2012
Last verified: August 2012
  Purpose

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 Intervention
Cardiovascular Diseases
Inflammation
Dyslipidemias
Blood Pressure
Hyperglycemia
Other: Prudent Diet
Other: Typical Western Diet

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: 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

Resource links provided by NLM:


Further study details as provided by McMaster University:

Primary Outcome Measures:
  • gene expression measuring ANRIL production [ Time Frame: baseline and 2 weeks ] [ Designated as safety issue: No ]
  • epigenetic marks [ Time Frame: baseline and 2 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • high-sensitivity C-reactive protein [ Time Frame: baseline and 2 weeks ] [ Designated as safety issue: No ]
    Biomarker of inflammation

  • interferon-alpha-21 [ Time Frame: baseline and 2 weeks ] [ Designated as safety issue: No ]
    Biomarker of inflammation

  • interferon-gamma [ Time Frame: baseline and 2 weeks ] [ Designated as safety issue: No ]
    Biomarker of inflammation

  • interleukin-1-alpha [ Time Frame: baseline and 2 weeks ] [ Designated as safety issue: No ]
    Biomarker of inflammation

  • total cholesterol [ Time Frame: baseline and 2 weeks ] [ Designated as safety issue: No ]
    lipid risk factor for cardiovascular disease

  • low-density lipoprotein-cholesterol [ Time Frame: baseline and 2 weeks ] [ Designated as safety issue: No ]
    lipid risk factor for cardiovascular disease

  • high-density lipoprotein-cholesterol [ Time Frame: baseline and 2 weeks ] [ Designated as safety issue: No ]
    lipid risk factor for cardiovascular disease

  • apolipoprotein-B [ Time Frame: baseline and 2 weeks ] [ Designated as safety issue: No ]
    lipid risk factor for cardiovascular disease

  • fasting glucose [ Time Frame: baseline and 2 weeks ] [ Designated as safety issue: No ]
    indicator of insulin resistance

  • systolic blood pressure [ Time Frame: baseline and 2 weeks ] [ Designated as safety issue: No ]
    mmHg

  • diastolic blood pressure [ Time Frame: baseline and 2 weeks ] [ Designated as safety issue: No ]
    mmHg

  • interleukin-6 [ Time Frame: baseline and 2 weeks ] [ Designated as safety issue: No ]
    Biomarker of inflammation


Estimated Enrollment: 80
Study Start Date: July 2012
Estimated Study Completion Date: July 2013
Estimated Primary Completion Date: July 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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).

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.

  Eligibility

Ages Eligible for Study:   18 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

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)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01658137

Contacts
Contact: Sujane Kandasamy, HBScI, BA (905) 525-9140 ext 22091 kandas3@mcmaster.ca

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

Additional Information:
Publications:
Responsible Party: Sonia Anand, Professor, McMaster University
ClinicalTrials.gov Identifier: NCT01658137     History of Changes
Other Study ID Numbers: DIGEST-Pilot
Study First Received: July 28, 2012
Last Updated: August 1, 2012
Health Authority: Canada: Ethics Review Committee

Keywords provided by McMaster University:
diet
dietary pattern
gene
gene expression
epigenomics
diet-gene interaction
inflammation
9p21
fruits
vegetables

Additional relevant MeSH terms:
Cardiovascular Diseases
Hyperglycemia
Inflammation
Dyslipidemias
Glucose Metabolism Disorders
Metabolic Diseases
Pathologic Processes
Lipid Metabolism Disorders

ClinicalTrials.gov processed this record on August 21, 2014