Clinical trial NCT05500976: Metabolomics Initiative: Mediterranean-amplified vs Habitual Western Diet on Food Signatures, Health, and Microbiome
Official title: Metabolomics INItiative: Effects of a MEDiterranean-amplified vs Habitual Western Diet on Biomarker Signatures, Cardiometabolic Health, and the Microbiome
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: NA
Conditions: Dietary Habits
Keywords: Mediterranean diet
Foodomics
Metabolomics
Food-specific signatures
Cardiometabolic health
Microbiome
Lead sponsor: University of Colorado, Denver
Sponsor class: OTHER
Collaborators: name: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
name: National Cattlemen's Beef Association
name: Purdue University
First posted: 2022-08-15
Enrollment: 22
Sex: ALL
Minimum age (years): 30
Maximum age (years): 69
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: Participants will complete a 16-week randomized cross-over semi-controlled feeding study comparing two isocaloric dietary interventions. The two diets will be a 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 their habitual/Western (Western) diet,

Participants will be randomized (1:1) to start one of the dietary interventions, with subsequent assignment to the other upon completion of the first. A permuted block randomization scheme using block size of 2 and stratification by sex will be utilized to ensure balance between intervention order and number of males and females in each arm.
Primary purpose: BASIC_SCIENCE

Brief 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.

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: Foodomics
timeFrame: Baseline to endline changes in food-specific compounds over each 4-week dietary intervention period
Secondary outcomes:
measure: Cardiometabolic Health - IL-6
timeFrame: Baseline to endline changes over each 4-week dietary intervention period
measure: Cardiometabolic Health - TNF-alpha
timeFrame: Baseline to endline changes over each 4-week dietary intervention period
measure: Cardiometabolic Health - C-reactive protein
timeFrame: Baseline to endline changes over each 4-week dietary intervention period
measure: Cardiometabolic Health - alpha-1-acid glycoprotein
timeFrame: Baseline to endline changes over each 4-week dietary intervention period
measure: Cardiometabolic Health - Total Cholesterol
timeFrame: Baseline to endline changes over each 4-week dietary intervention period
measure: Cardiometabolic Health - LDL Cholesterol
timeFrame: Baseline to endline changes over each 4-week dietary intervention period
measure: Cardiometabolic Health - HDL Cholesterol
timeFrame: Baseline to endline changes over each 4-week dietary intervention period
measure: Cardiometabolic Health - Triglycerides
timeFrame: Baseline to endline changes over each 4-week dietary intervention period
measure: Cardiometabolic Health - Blood Pressure
timeFrame: Baseline to endline changes over each 4-week dietary intervention period
measure: Cardiometabolic Health - Insulin
timeFrame: Baseline to endline changes over each 4-week dietary intervention period
measure: Cardiometabolic Health - Glucose
timeFrame: Baseline to endline changes over each 4-week dietary intervention period
measure: Cardiometabolic Health - Adipokines
timeFrame: Baseline to endline changes over each 4-week dietary intervention period
measure: Gut Microbiota
timeFrame: Baseline to endline changes over each 4-week dietary intervention period
Other outcomes:
Locations:
city: Aurora
country: United States
facility: University of Colorado School of Medicine
state: Colorado
Study officials:
affiliation: University of Colorado School of Medicine
name: Nancy F Krebs, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Colorado School of Pharmacy
name: Nichole Reisdorph, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Purdue University
name: Wayne Campbell, PhD
role: PRINCIPAL_INVESTIGATOR
References: