Age-associated Arterial Dysfunction, Western Diet, and Aerobic Exercise: Role of the Gut Microbiome

The risk of developing cardiovascular diseases increases with aging largely due to age-related declines in the function of arteries (arterial dysfunction), which are influenced by common lifestyle factors such as consumption of a "Western" diet and lack of sufficient physical activity; thus, it is important to study how these factors interact to affect artery function. This study will determine whether changes to the gut microbiome (the collection of bacteria and other "microbes" living in the intestinal tract) with aging, Western diet consumption and aerobic exercise influence arterial function, and the biological pathways (mechanisms) involved. Specifically, the investigators will perform a randomized, single-blind, controlled feeding crossover study design (comparing Western diet to non-Western diet consumption) in young and older, exercising and non-exercising healthy adults to determine the time course effects (temporal association) of diet on the gut microbiome and arterial function. Overall, this research has potential to establish the gut microbiome as a possible target for treating/preventing age-related arterial dysfunction and reducing the risk of age-associated cardiovascular diseases.

Study Overview

• Status: Recruiting
• Conditions: Aging
• Intervention / Treatment: Other: Western Diet; Other: Non-Western Diet

Detailed Description

In order to investigate how age-related changes to the gut microbiome, as modulated by Western diet and exercise, influences arterial function in humans, the investigators will capitalize on the plasticity of the gut microbiome to dietary perturbations. A randomized, single-blind, 2x1-week dietary intervention crossover study (with 3 week washout) will be conducted in young (18-29 years) and old (60-79 years), exercising and non-exercising, male and female adults from all races and ethnic backgrounds. Testing will take place on the University of Colorado Boulder main campus at the Clinical and Translational Research Center (CTRC - located in the Wardenburg Health Center). Subjects will undergo telephone and in-person CTRC screening, with those eligible assigned to either Group A or Group B using block randomization stratified by age and exercise status. Group A will undergo isocaloric WD feeding (high fat [40%], high sugar [25%], low fiber [15g], low nutrient) during Phase 1 (first 1-week treatment period) and non-WD feeding (low-fat [25%], low sugar [15%], high fiber [22g], high nutrient) during Phase 2 (second 1-week treatment period). Group B will undergo the dietary interventions in the opposite order. Phases 1 and 2 will be separated by a 3-week washout period to prevent carry over effects. During each 1-week intervention period, fecal swabs will be collected daily to characterize the gut microbiome and vascular function, will be measured at baseline and after 2 and 7 days of controlled feeding to gain insight into the temporal relation between these outcomes.

• Study Type: Interventional
• Enrollment (Anticipated): 120
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Kara Lubieniecki, MS; Phone Number: 303-735-6410; Email: ipalab@colorado.edu
• Study Contact Backup: Name: Vienna E Brunt, PhD; Phone Number: 303-735-4936; Email: vienna.brunt@colorado.edu

Study Locations

• United States
  • Colorado
    • Boulder, Colorado, United States, 80309
      • Recruiting
      • University of Colorado Boulder
      • Contact: Kara Lubieniecki, MS; Phone Number: 303-735-6410; Email: ipalab@colorado.edu
      • Contact: Vienna E Brunt, PhD; Phone Number: 303-735-4936; Email: vienna.brunt@colorado.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 79 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Age 18-29 or 60-79 years
• Participating in < 30 min aerobic exercise < 2x/wk for >3 years OR > 45 min vigorous aerobic exercise > 4x/wk for > 3 yrs
• Currently consuming levels of dietary fat intake with the 40th-60th percentile of Americans based on the NHANES survey (29-37% calories from fat)
• Healthy (no clinical disease)
• Body mass index < 30 kg/m2
• Ankle-brachial blood pressure index > 0.9
• Total cholesterol < 240 mg/dl
• Fasting plasma glucose < 110 mg/dl
• Weight stable in the past 6 months

Exclusion Criteria:

• Current or past (within 3 months of screening) use of dietary supplements, anti-inflammatory medications, drugs known to affect the gut microbiome (antibiotics, pre/probiotics, antifungals, antivirals, antiparasitics), or gastrointestinal-targeted drugs (proton pump inhibitors, H2 receptor antagonists, laxatives, antidiarrheal medications)
• Current of past (within 5 years) smoking
• Major change in health status in the last 6 months
• Chronic clinical diseases (e.g., inflammatory bowl diseases, cardiovascular disease, diabetes, neurological disorders, dementia or other brain diseases of aging)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Western diet first; To receive Western diet controlled feeding first, followed by non-Western diet controlled feeding	Other: Western Diet; high fat (40%), high sugar (25%) and low fiber (15g/day); Other: Non-Western Diet; low fat (25%), low sugar (15%), high fiber (30g/day)
Other: Non-Western diet first; To receive non-Western diet controlled feeding first, followed by Western diet controlled feeding	Other: Western Diet; high fat (40%), high sugar (25%) and low fiber (15g/day); Other: Non-Western Diet; low fat (25%), low sugar (15%), high fiber (30g/day)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in the gut microbiome	Sterile fecal swabs will be collected and analyzed using 16S rRNA sequencing	7 days
Change in endothelial function	Brachial artery flow-mediated dilation	7 days
Change in arterial stiffness	Carotid-femoral pulse wave velocity	7 days

Collaborators and Investigators

• Sponsor: University of Colorado, Boulder
• Collaborators: University of California, San Diego

Study record dates

Study Major Dates

• Study Start (Actual): March 15, 2018
• Primary Completion (Anticipated): December 31, 2021
• Study Completion (Anticipated): December 31, 2021

Study Registration Dates

• First Submitted: November 1, 2017
• First Submitted That Met QC Criteria: November 2, 2017
• First Posted (Actual): November 7, 2017

Study Record Updates

• Last Update Posted (Actual): October 28, 2021
• Last Update Submitted That Met QC Criteria: October 27, 2021
• Last Verified: October 1, 2021

More Information

Terms related to this study

• Other Study ID Numbers: 16-0633

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No