Metabolomics Initiative: Mediterranean-amplified vs Habitual Western Diet on Food Signatures, Health, and Microbiome

Dietary Habits Clinical Trial

— Mini-MED  

Official title:

Metabolomics INItiative: Effects of a MEDiterranean-amplified vs Habitual Western Diet on Biomarker Signatures, Cardiometabolic Health, and the Microbiome

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05500976
• Other study ID #: 21-4563
• Secondary ID: R01DK1139572070
• Status: Recruiting
• Phase: N/A
• Start date: November 21, 2022
• Est. completion date: December 31, 2024

Study information

• Verified date: September 2023
• Source: University of Colorado, Denver
• Contact: Nancy F Krebs, MD
• Phone: 303.724.3260
• Email: nancy.krebs[@]cuanschutz.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study plans to learn more about how consuming a diet with foods typical to a Mediterranean Diet such as whole grains, fruits and vegetables in a Western-style diet compares to eating a typical Western-style diet. This study will look at how diet affects overall health including risk factors for heart disease, gut health and inflammation as well as underlying mechanisms linking whole food to health. Findings from this study will potentially inform effective dietary recommendations and interventions, thereby reducing chronic disease in humans.

Description:

The investigators propose to conduct a 16-week randomized, cross-over, semi-controlled feeding study of two isocaloric dietary interventions: 1. Mediterranean-amplified habitual/Western (mini-MED) diet, containing 500 kcal/day from Mediterranean target foods (such as raspberries, avocado, red bell pepper, basil, walnuts, chickpeas, oats, salmon); and

2. Habitual/Western (Western) diet, containing 500 kcal/day from non-Mediterranean target foods (such as potato, beef, sour cream, refined grain bread, chocolate dessert); among individuals who are not already consuming a Mediterranean-style dietary pattern. Participants will have overweight or obesity and meet criteria for Metabolic Syndrome (MetS), and therefore be at increased risk of cardiometabolic disease (CMD).

The primary goal is to validate results from metabolomics analyses of foods and biospecimens from a completed Mediterranean-style dietary intervention in a prospective feeding trial. Secondary aims are to evaluate impacts of incremental changes in diet on cardiometabolic health and microbiome structure/function. The primary hypothesis is that pre-defined metabolomics signatures in participant biospecimens will be responsive to dietary intakes and reproducible within individuals over time. The secondary hypotheses are that a Mediterranean-amplified diet will lead to improvements in cardiometabolic health and changes in microbiome structure/function over time and compared to a habitual Western diet.

Aim 1: Test reproducibility of pre-defined signatures from Mediterranean target foods provided in mini-MED in biospecimens (blood/urine) within individuals over time. Participants will complete a 16-week randomized cross-over dietary intervention of mini-MED vs Western diet. The investigators hypothesize that: (1) novel food-specific compounds will increase in participant biospecimens after consumption of mini-MED and decrease during Western diet, and (2) established biomarkers of fruit/vegetable intake (e.g., plasma and skin carotenoids, urine polyphenols) and other target foods (e.g., plasma alkylresorcinols, astaxanthin) will increase after consumption of mini-MED.

Aim 2: Determine the impact of mini-MED on cardiometabolic health. Cardiometabolic health indicators (e.g., blood pressure, lipid panel, inflammatory cytokines, indicators of subclinical inflammation) will be assessed pre- and post- each intervention. The investigators hypothesize that consumption of mini-MED will lead to improvements in cardiometabolic health indicators (e.g., reductions in blood pressure, total cholesterol, LDL cholesterol, triglycerides, C-reactive protein, bioactive lipids; increases in HDL cholesterol) over time and compared to Western diet.

Aim 3: Evaluate changes in microbiota community structure/function in response to mini-MED. Microbiome structure (taxonomy) and function (metagenomics) will be assessed pre- and post- each intervention. The investigators hypothesize that consumption of mini-MED will lead to increases in microbiome diversity and enrichment in taxa associated with increased production of health-promoting compounds (e.g., short chain fatty acids) over time and compared to Western diet.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 40
• Est. completion date: December 31, 2024
• Est. primary completion date: March 31, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 30 Years to 69 Years

Eligibility

Inclusion Criteria:

• Overweight or obesity (BMI 25-37 kg/m2) and weight-stable;

• Age 30-69 years;

• Nonsmoker (including tobacco, marijuana, and other inhaled substances);

• Consistent physical activity levels for 3 months prior to and throughout the study period;

• Stable medication use for 6 months prior to and throughout the study period;

• Having at least three components of Metabolic Syndrome (MetS): i.e., impaired fasting glucose, hypertension, central adiposity (waist circumference = 94 cm or 80 cm, for men and women, respectively), fasting hypertriglyceridemia, and/or low levels of HDL cholesterol17 OR on medication for the treatment of hyperglycemia, hypertension, or hypercholesterolemia in lieu of meeting the corresponding MetS component;

• Report of baseline consumption of a habitual diet not meeting criteria for a Mediterranean-style dietary pattern, defined as a score of <5 as assessed via the Mediterranean Diet Assessment Tool

• Follows an omnivorous diet and willing to consume all provided foods (e.g., will eat salmon, fruits/vegetables, beef);

• Willingness to refrain from consumption of nutritional supplements, herbal supplements, botanical supplements, and pre- or probiotics aside from those prescribed by a physician for the duration of the study;

• Willingness to come to the CTRC biweekly for clinical assessments and biospecimen collection;

• No plans to relocate or for extended travel (>1 week) within next 6 months; and

• Capable and willing to provide informed consent

Exclusion Criteria:

• Use of medications contraindicating increased consumption of fruits/vegetables (e.g., warfarin);

• Diagnosis of acute or chronic condition impacting appetite, food intake, and/or the metabolism and absorption of foods to be provided (e.g., Crohn's disease, Celiac disease, Ulcerative colitis, short bowel syndrome, chronic diarrhea);

• Impaired liver or kidney function;

• Food allergies to foods provided in either dietary intervention;

• Vegetarian, vegan; and

• For females: pregnant or lactating or planning to become pregnant during study period

Related Conditions & MeSH terms

• Dietary Habits

Intervention

Other:
• Semi-controlled dietary intervention - Western
Participants will complete a 2-week washout prior to a 16-week randomized, crossover semi-controlled feeding study of mini-MED vs Western diet. Each diet intervention will last four weeks, with 500 kcal/day of target Western diet foods (eg, beef, potatoes, bread, sour cream) provided during each intervention and will be repeated twice.
• Semi-controlled dietary intervention - MiniMed
Participants will complete a 2-week washout prior to a 16-week randomized, crossover semi-controlled feeding study of mini-MED vs Western diet. Each diet intervention will last four weeks, with 500 kcal/day of target Mediterranean foods (eg, oatmeal, salmon, nuts, basil, olive oil, fruits) provided during each intervention and will be repeated twice.

Locations

Country	Name	City	State
United States	University of Colorado School of Medicine	Aurora	Colorado

Sponsors (4)

Lead Sponsor	Collaborator
University of Colorado, Denver	National Cattlemen's Beef Association, National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), Purdue University

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Foodomics	Change in the number of unique to food compounds (i.e., putative biomarkers of intake) from baseline to end of each diet intervention period in participant serum samples.	Baseline to endline changes in food-specific compounds over each 4-week dietary intervention period
Secondary	Cardiometabolic Health - IL-6	Changes in blood inflammatory markers including IL-6 over time and between the two dietary interventions.	Baseline to endline changes over each 4-week dietary intervention period
Secondary	Cardiometabolic Health - TNF-alpha	Changes in blood inflammatory markers including TNF-alpha over time and between the two dietary interventions.	Baseline to endline changes over each 4-week dietary intervention period
Secondary	Cardiometabolic Health - C-reactive protein	Changes in blood inflammatory markers including C-reactive protein over time and between the two dietary interventions.	Baseline to endline changes over each 4-week dietary intervention period
Secondary	Cardiometabolic Health - alpha-1-acid glycoprotein	Changes in blood inflammatory markers including alpha-1-acid glycoprotein over time and between the two dietary interventions.	Baseline to endline changes over each 4-week dietary intervention period
Secondary	Cardiometabolic Health - Total Cholesterol	Changes in fasting total cholesterol over time and between the two dietary interventions.	Baseline to endline changes over each 4-week dietary intervention period
Secondary	Cardiometabolic Health - LDL Cholesterol	Changes in fasting LDL cholesterol over time and between the two dietary interventions.	Baseline to endline changes over each 4-week dietary intervention period
Secondary	Cardiometabolic Health - HDL Cholesterol	Changes in fasting HDL cholesterol over time and between the two dietary interventions.	Baseline to endline changes over each 4-week dietary intervention period
Secondary	Cardiometabolic Health - Triglycerides	Changes in fasting triglycerides over time and between the two dietary interventions.	Baseline to endline changes over each 4-week dietary intervention period
Secondary	Cardiometabolic Health - Blood Pressure	Changes in blood pressure over time and between the two dietary interventions.	Baseline to endline changes over each 4-week dietary intervention period
Secondary	Cardiometabolic Health - Insulin	Changes in fasting blood insulin over time and between the two dietary interventions.	Baseline to endline changes over each 4-week dietary intervention period
Secondary	Cardiometabolic Health - Glucose	Changes in fasting blood glucose over time and between the two dietary interventions.	Baseline to endline changes over each 4-week dietary intervention period
Secondary	Cardiometabolic Health - Adipokines	Changes in circulating plasma adipokines over time and between the two dietary interventions.	Baseline to endline changes over each 4-week dietary intervention period
Secondary	Gut Microbiota	Changes in diversity and community composition of the gut microbiota.	Baseline to endline changes over each 4-week dietary intervention period