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The Addition of Whole Grains to the Diets of Adults: A Study of Digestive Health and Natural Defenses

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ClinicalTrials.gov Identifier: NCT01902394
Recruitment Status : Completed
First Posted : July 18, 2013
Last Update Posted : May 21, 2015
Sponsor:
Collaborators:
General Mills Inc.
Tufts Medical Center
Information provided by (Responsible Party):
Simin Meydani, Tufts University

Brief Summary:

The purpose of this study is to determine if substituting whole grains for refined grains in the diets of healthy adults over a period of 6 weeks alters the composition of the bacteria in the gut, and has beneficial effects on immune function, digestive health, cardiovascular health, regulation of body weight and composition, and vitamin K status.

The investigators hypothesize that whole grain consumption over a period of 6 weeks will alter the gut microflora toward a more beneficial bacterial profile, improve the immune response while reducing oxidative stress and inflammatory markers, have favorable effects on factors influencing the regulation of body weight and composition,increase bacterial vitamin K synthesis, and beneficially effect surrogate markers of cholesterol synthesis/absorption, vitamin D concentrations, and whole genome DNA methylation patterns. In statin users it is hypothesized that, consumption of whole grains will alter statin pharmacokinetics by decreasing rate of statin absorption, resulting in more sustained plasma concentrations.


Condition or disease Intervention/treatment Phase
Digestive Health and Immune Function Other: Whole grains Other: Refined grains Not Applicable

Detailed Description:
This study is a randomized parallel-arm trial using a six-week dietary intervention following a 2 week run-in period. Healthy volunteers will be randomized to two groups (n=40/group), and consume either a diet rich in whole grains or a diet rich in refined grains provided at estimated energy requirements for 6 weeks. Outcomes will be measured during the run-in period and at week 6 of the intervention. To control for variation in microbiota an additional 10 volunteers will serve as "negative controls" and not undergo any diet intervention.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 108 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Official Title: The Addition of Whole Grains to the Diets of Adults: A Study of Digestive Health and Natural Defenses
Study Start Date : June 2012
Actual Primary Completion Date : September 2014
Actual Study Completion Date : September 2014

Arm Intervention/treatment
Experimental: Whole grain rich diet
Participants in the whole grain (WG) group will receive a diet providing 100% of energy requirements in a diet rich in whole grains.
Other: Whole grains
Following completion of the baseline period (a 2-week run-in phase), participants in the WG group will receive a diet providing 100% of energy requirements in a diet rich in whole grains and the RG group will be provided with 100% of energy requirements in a diet rich in refined grains but otherwise similar to the WG diet for 6 weeks.

Placebo Comparator: Refined grain rich diet
Participants in the refined grain (RG) group will receive a diet providing 100% of energy requirements in a diet rich in refined grains.
Other: Refined grains
Following completion of the baseline period (a 2-week run-in phase), participants in the WG group will receive a diet providing 100% of energy requirements in a diet rich in whole grains and the RG group will be provided with 100% of energy requirements in a diet rich in refined grains but otherwise similar to the WG diet for 6 weeks.

No Intervention: Negative control
Subjects randomized to the negative control group will consume their own usual diet (i.e. not receive foods and beverages from the study).



Primary Outcome Measures :
  1. change in T Cell-mediated immunity [ Time Frame: week 2 of washout diet and week 6 of diet intervention ]
    Delayed-type hypersensitivity (DTH) and lymphocyte proliferation will be measured at baseline (week 2 of washout period) and at week-6 of the diet intervention to assess adaptive immune function, specifically T cell-mediated immunity.

  2. change in Lymphocyte proliferation [ Time Frame: week 2 of washout diet and week 6 of diet intervention ]
    Whole blood collected at baseline (week 2 of washout period) and at week-6 of the diet intervention will be investigated for the ability of lymphocytes to proliferate by quantifying the incorporation of tritium following mitogen stimulation.

  3. change in Natural Killer Function [ Time Frame: week 2 of washout diet and week 6 of diet intervention ]
    The ability of peripheral blood mononuclear cells to bind and kill leukemia cells will be measured at baseline (week 2 of washout period) and at week-6 of the diet intervention

  4. change in Cytokines [ Time Frame: week 2 of washout diet and week 6 of diet intervention ]
    Peripheral blood and stool samples will be analyzed at baseline (week 2 of washout diet) and week-6 of diet intervention for cytokines.

  5. change in Salivary immunoglobulin A (IgA) [ Time Frame: week 2 of washout diet and week 6 of intervention diet ]
    Salivary IgA will be analyzed at baseline (week 2 of washout period) and at week-6 of the diet intervention.


Secondary Outcome Measures :
  1. change in gut microbiota composition [ Time Frame: week 2 of washout diet and week 6 of intervention diet ]
    Phylogenetic composition and relative abundance of bacteria in stool will be analyzed from 24-hour fresh sample collected at baseline (week 2 of washout diet) and at week 6 of intervention diet

  2. change in cardiovascular health risk factors [ Time Frame: week 2 of washout diet and week 6 of intervention diet ]
    Consumption of the whole grain (WG) diet will be beneficial for multiple outcomes of cardiovascular health including a favorable blood lipid profile (low density lipoprotein, very low-density lipoprotein, high density lipoprotein, total cholesterol and triglycerides), and a decrease in blood pressure, and in oxidative stress status (secondary hypothesis).

  3. change in vitamin K status [ Time Frame: week 2 of washout diet and week 6 of intervention diet ]
    Fecal menaquinones concentrations; Fasting serum phylloquinone and menaquinones concentration from 72-hour stool collected at baseline (week 2 of washout diet) and at week 6 of intervention diet

  4. change in body composition [ Time Frame: week 2 of washout diet and week 6 of intervention diet ]
    Fat and fat free mass; waist and hip circumference

  5. change in appetite [ Time Frame: Weekly for 8 weeks ]
    Visual analog scales to assess hunger, fullness and satisfaction while on the study diet

  6. change in fasting gut hormone concentration [ Time Frame: week 2 of washout diet and week 6 of intervention diet ]
    Plasma glucagon-like peptide-1 and peptide-YY will be measured from blood samples collected at baseline (week 2 of washout diet) and week 6 of intervention diet

  7. change in fasting serum leptin [ Time Frame: week 2 of washout diet and week 6 of intervention diet ]
  8. change in glycemic regulation [ Time Frame: week 2 of washout diet and week 6 of intervention diet ]
    48 hr continuous glucose monitoring; fasting serum glucose; fasting serum insulin; HOMA-IR

  9. change in resting energy metabolism [ Time Frame: week 2 of washout diet and week 6 of intervention diet ]
    Resting energy expenditure; substrate oxidation at rest

  10. change in eating behaviors [ Time Frame: week 2 of washout diet and week 6 of intervention diet ]
    Questionnaires will be administered at baseline (week 2 of washout diet) and week 6 of intervention diet

  11. change in quality of life [ Time Frame: week 2 of washout diet and week 6 of intervention diet ]
    Questionnaires will be administered at baseline (week 2 of washout diet) and week 6 of intervention diet

  12. change in breath hydrogen and methane [ Time Frame: week 2 of washout diet and week 6 of intervention diet ]
  13. change in stool pH [ Time Frame: week 2 of washout diet and week 6 of intervention diet ]
    Will be measured from 72-hour stool sample collected at baseline (week 2 of washout diet) and week 6 of intervention diet

  14. change in 72hr fecal weight [ Time Frame: week 2 of washout diet and week 6 of intervention diet ]
    Will be measured from 72-hour stool sample collected at baseline (week 2 of washout diet) and week 6 of intervention diet

  15. change in stool water content [ Time Frame: week 2 of washout diet and week 6 of intervention diet ]
    Will be measured from 72-hour stool sample collected at baseline (week 2 of washout diet) and week 6 of intervention diet

  16. change in total stool anaerobic and aerobic bacterial counts [ Time Frame: week 2 of washout diet and week 6 of intervention diet ]
    Will be measured from 72-hour stool sample collected at baseline (week 2 of washout diet) and week 6 of intervention diet

  17. change in stool energy content [ Time Frame: week 2 of washout diet and week 6 of intervention diet ]
    Will be measured from 72-hour stool sample collected at baseline (week 2 of washout diet) and week 6 of intervention diet

  18. change in DNA methylation [ Time Frame: week 2 of washout diet and week 6 of intervention diet ]
  19. change in concentrations of the cholesterol synthesis (squalene, desmosterol, lathosterol) and absorption (campesterol, sitosterol, cholestanol) markers [ Time Frame: week 2 of washout diet and week 6 of intervention diet ]
    Plasma squalene, desmosterol, lathosterol), campesterol, sitosterol, and cholestanol concentrations will be measured at baseline (week 2 of washout diet) and week 6 of intervention diet

  20. change in serum vitamin D [ Time Frame: week 2 of washout diet and week 6 of intervention diet ]


Information from the National Library of Medicine

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Ages Eligible for Study:   40 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Subjects Inclusion Criteria

  • Healthy male and female subjects aged 40-65 y (women must be > 1 year postmenopausal or had both ovaries removed, if premenopausal).
  • Body mass index (BMI) 20-35 kg/m.2
  • Pass screening blood and urine tests

    • Creatinine ≤ 1.5 mg/dL
    • glutamic oxaloacetic transaminase/serum glutamate pyruvate transaminase/total bilirubin ≤ twice the upper limit of normal range
    • Fasting glucose <125 mg/dL
    • hematocrit ≥ 32%
    • white blood cell count ≥ 1.8 x 103/mm3 (M)
    • PLT ≥ 100 x 103/mm3 (thou/µL)
  • Must be willing to be randomized.
  • Those randomized to either the WG or RG groups must be willing to consume only study foods and beverages provided.

Exclusion Criteria

  • Self reported weight change >4kg within the past 3 months.
  • Have participated in a weight loss program within the last 3-months; eligible if in weight reduction program to maintain body weight.
  • Not willing to reduce habitual daily fiber intake (including prebiotics) within 2 wk prior to enrollment to < ~7g/1000kcal/d for men, or <~8g/1000kcal/d for women if currently consuming greater amounts.
  • Not willing to stop consumption of probiotic or prebiotic supplements within 2 weeks prior to start of study if currently taking these, as well as during study participation.
  • Vegetarian diet.
  • Not willing to stop taking multivitamins, and supplements (with the exception of vitamin D and calcium), including fish oil or n-3 fatty acids and herbal supplements, for 30 days prior to or during study participation, if currently taking these.
  • Regular use of laxatives, stool softeners, or anti-diarrheal medications, and medications influencing food intake and/or appetite.
  • Not willing to undergo a 3-month washout period after colonoscopy prior to enrollment, and not willing to defer colonoscopy until after study completion.
  • Eating disorder within the past 10 years.
  • Disinhibited eating behavior as indicated by a score above 12 on the Three Factor Eating Questionnaire.
  • Food allergies or aversions or other issues with foods that would preclude use of study diets, including gluten, milk, nuts, or eggs.
  • Individuals identified during screening as having barriers expected to deter compliance with dietary requirements (e.g., stated dislike of study foods, inadequate resources to store and reheat meals, inability to adhere to food pick-up schedule).
  • Alcohol consumption >2 drinks per day.
  • Not willing to abstain from alcohol consumption during the study.
  • Smoking or using nicotine containing products in the last 6 months.
  • Use of aspirin, non-steroidal anti-inflammatory medications (NSAIDs) or antihistamine prescribed by a physician or clinician, or the inability to discontinue the use of these substances for 72 hrs before first day blood draw until 48 hrs after DTH implant (i.e. after second reading).
  • Use of anabolic steroids, insulin, growth hormone or testosterone.
  • Type I or type II diabetes.
  • Uncontrolled major illnesses. (Will include if stable on drugs used to control cardiovascular, liver, and renal diseases, asthma, and dysphagia).
  • Current use of proton pump inhibitors and H2 blockers to control acid-reflux/heart burn
  • Use of medications which interfere with energy metabolism including oral glycemic agents and insulin.
  • Uncontrolled hypertension as determined by study physician or nurse.
  • Use of immunosuppressive drugs.
  • Active cancer or current cancer diagnosis (except non-melanoma skin cancer).
  • Active infection within 2 weeks of study enrollment, blood draws or skin tests; however, may participate if admission is postponed or study activity is rescheduled > 2 weeks after resolution of symptoms.
  • Any antibiotic use within the past 3 months, except topical antibiotic use.
  • History of dysphagia, malabsorptive disorders, inflammatory bowel disease or other gastrointestinal disorders such as ulcerative colitis, Crohn's disease, celiac disease , chronic diarrhea or constipation.
  • Gastric bypass or other surgery for weight loss.
  • Splenectomy or partial splenectomy.
  • Autoimmune diseases such as rheumatoid arthritis and psoriasis. Autoimmune thyroid disease that has been treated and with stable replacement doses is not an exclusion.
  • Taking warfarin or coumadin any time during the previous 6 months.
  • Current diagnosis of or treatment for psychosis (i.e. schizophrenia, etc.). Include depression if has been stable on treatment regimen for > 6 months.
  • Blindness or deafness not corrected with use of glasses and hearing aids.
  • Does not speak English; due to insufficient funds to hire a translator and to get all study materials translated into another language to allow us to recruit non-English speaking participants non-English speakers will not be eligible to participate.

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): NCT01902394


Locations
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United States, Massachusetts
HNCRA at Tufts University
Boston, Massachusetts, United States, 02111
Sponsors and Collaborators
Tufts University
General Mills Inc.
Tufts Medical Center
Investigators
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Principal Investigator: Simin N Meydani, DVM, PhD Human Nutrition Research Center on Aging
Study Director: Junaidah B Barnett, MCH(N), PhD Human Nutrition Research Center on Aging

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Simin Meydani, Director of the Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts, Tufts University
ClinicalTrials.gov Identifier: NCT01902394     History of Changes
Other Study ID Numbers: 2720
First Posted: July 18, 2013    Key Record Dates
Last Update Posted: May 21, 2015
Last Verified: May 2015

Keywords provided by Simin Meydani, Tufts University:
digestive health and natural defenses