Effect of Dietary Flavonoids on Intestinal Microbiota, Intestinal Inflammation and Metabolic Syndrome

• ClinicalTrials.gov Identifier: NCT02728570
• Recruitment Status: Completed
• First Posted: April 5, 2016
• Last Update Posted: April 15, 2016
• Sponsor: Utah State University
• Information provided by (Responsible Party): Utah State University

Tracking Information

• First Submitted Date: March 30, 2016
• First Posted Date: April 5, 2016
• Last Update Posted Date: April 15, 2016
• Study Start Date: November 2013
• Actual Primary Completion Date: March 2015 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: March 30, 2016)

• Fecal calprotectin [ Time Frame: 6 weeks ]
  Primary endpoint for intestinal inflammation
• Serum C-reactive protein [ Time Frame: 6 weeks ]
  One of two primary endpoints for systemic inflammation
• Serum soluble tumor necrosis factor receptor-1 [ Time Frame: 6 weeks ]
  One of two primary endpoints for systemic inflammation
• Serum insulin [ Time Frame: 6 weeks ]
  Primary endpoint for insulin resistance

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: March 30, 2016)

• Fecal microbiome composition [ Time Frame: 6 weeks ]
  Includes relative abundances of operational taxonomic units and assigned taxonomy as well as alpha and beta diversity measurements
• Fecal short chain fatty acids [ Time Frame: 6 weeks ]
  Measure of fecal microbiome metabolic capabilities and includes acetate, propionate, butyrate, valerate and caproate.
• Fecal eosinophil protein X [ Time Frame: 6 weeks ]
  Secondary endpoint for intestinal inflammation
• Fecal myeloperoxidase [ Time Frame: 6 weeks ]
  Secondary endpoint for intestinal inflammation
• Intestinal permeability by four sugar differential absorption test [ Time Frame: 6 weeks ]
  Secondary endpoint for intestinal inflammation
• Serum endotoxin [ Time Frame: 6 weeks ]
  Secondary endpoint for intestinal inflammation
• Serum interleukin-6 [ Time Frame: 6 weeks ]
  Secondary endpoint for systemic inflammation
• Serum soluble tumor necrosis factor receptor-2 [ Time Frame: 6 weeks ]
  Secondary endpoint for systemic inflammation
• Serum fasting glucose [ Time Frame: 6 weeks ]
  Secondary endpoint for insulin resistance
• Calculated Homeostatic Model Assessment-Insulin Resistance [ Time Frame: 6 weeks ]
  Secondary endpoint for insulin resistance
• Serum C-peptide [ Time Frame: 6 weeks ]
  Secondary endpoint for insulin resistance
• Plasma lipids [ Time Frame: 6 weeks ]
  Secondary endpoint for insulin resistance. Includes LDL-cholesterol, HDL-cholesterol and triglycerides
• Blood pressure [ Time Frame: 6 weeks ]
  Secondary endpoint for insulin resistance. Includes systolic and diastolic blood pressure

• Original Secondary Outcome Measures: Same as current

Current Other Pre-specified Outcome Measures (submitted: March 30, 2016)

• Serum resistin [ Time Frame: 6 weeks ]
  Measure of adipocyte inflammation and systemic metabolism
• Serum visfatin [ Time Frame: 6 weeks ]
  Measure of adipocyte inflammation and systemic metabolism
• Serum adiponectin [ Time Frame: 6 weeks ]
  Measure of adipocyte inflammation and systemic metabolism
• Serum leptin [ Time Frame: 6 weeks ]
  Measure of adipocyte inflammation and systemic metabolism
• Body weight [ Time Frame: 6 weeks ]

• Original Other Pre-specified Outcome Measures: Same as current

Descriptive Information

• Brief Title: Effect of Dietary Flavonoids on Intestinal Microbiota, Intestinal Inflammation and Metabolic Syndrome
• Official Title: Effect of Dietary Flavonoids on Intestinal Microbiota, Intestinal Inflammation and Metabolic Syndrome
• Brief Summary: The investigators have hypothesized that dietary flavonoids reduce insulin resistance and subclinical inflammation secondary to reductions in intestinal inflammation and permeability and that these events are mediated through alterations in gut microbiota composition. To test this hypothesis, 30 overweight/obese men and women will be provided two well-controlled diets that are identical in macronutrient content (Protein, 17% en; Fat, 30% en; Carbohydrate, 53% en), but differ markedly in flavonoid content (Low Flavonoid Diet, 10 mg/1000 Kcals; High Flavonoid Diet, 340 mg/1000 Kcals). All meals for both diets will be prepared and fed for 6 weeks each in a randomized cross-over design with endpoints determined in duplicate during the last week of each diet period.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Not Applicable
• Study Design: Allocation: Randomized; Intervention Model: Crossover Assignment; Masking: Triple (Participant, Investigator, Outcomes Assessor); Primary Purpose: Basic Science

Condition

• Metabolic Syndrome X
• Inflammation

Intervention

• Other: High Dietary Flavonoids
  A prepared diet consisting of whole foods with a macronutrient composition of 17% en from protein, 30% en from fat and 53% energy from carbohydrate and containing high levels of dietary flavonoids including anthocyanins, flavanones, flavan-3-ols, flavonols, flavones, and polyflavonoids.
• Other: Low Dietary Flavonoids
  A prepared diet consisting of whole foods with a macronutrient composition of 17% en from protein, 30% en from fat and 53% energy from carbohydrate and containing low levels of dietary flavonoids including anthocyanins, flavanones, flavan-3-ols, flavonols, flavones, and polyflavonoids.

Study Arms

• Experimental: Low Flavonoids then High Flavonoids
  Participants receive a prepared diet with Low Dietary Flavonoids (10 mg of flavonoids/1000 Kcals) for six weeks. After a minimum washout period of 2 weeks, participants receive a prepared diet with High Dietary Flavonoids (340 mg of flavonoids/1000 Kcals) for six weeks.
  Interventions:

  • Other: High Dietary Flavonoids
  • Other: Low Dietary Flavonoids
• Experimental: High Flavonoids then Low Flavonoids
  Participants receive a prepared diet with High Dietary Flavonoids (340 mg of flavonoids/1000 Kcals) for six weeks. After a minimum washout period of 2 weeks, participants receive a prepared diet with Low Dietary Flavonoids (10 mg of flavonoids/1000 Kcals) for six weeks.
  Interventions:

  • Other: High Dietary Flavonoids
  • Other: Low Dietary Flavonoids

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: March 30, 2016): 30
• Original Actual Enrollment: Same as current
• Actual Study Completion Date: October 2015
• Actual Primary Completion Date: March 2015 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• BMI between 25 and 35 kg/m2

Exclusion Criteria:

• Documented presence of atherosclerotic disease;
• Diabetes mellitus
• Uncontrolled hypertension
• Renal, hepatic, endocrine, gastrointestinal or other systemic disease
• For women, pregnancy, breast feeding or postpartum < 6 months
• History of drug or alcohol abuse
• History of depression or mental illness requiring hospitalization within the last 12 months
• Use of antibiotics within the last 6 months
• Multiple food allergies or significant food preferences or restrictions that would interfere with diet adherence
• Chronic use of over-the-counter medication which would interfere with study endpoints including NSAIDS, laxatives and antacids
• Lifestyle or schedule incompatible with the study protocol
• Other medical, psychiatric, or behavioral conditions that in the view of the principal investigator may present a safety hazard to the participant or interfere with study participation or the ability to follow the intervention protocol.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 70 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT02728570
• Other Study ID Numbers: USU #5483
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided

IPD Sharing Statement

• Plan to Share IPD: Yes
• Plan Description: De-identified individual data will be deposited into a public repository as the data are published.

• Responsible Party: Utah State University
• Study Sponsor: Utah State University
• Collaborators: Not Provided

Investigators

• Principal Investigator: Michael Lefevre, PhD; Utah State University

• PRS Account: Utah State University
• Verification Date: April 2016