High Protein Diet and Atherosclerosis

NCT05235464 | Recruiting DMC

• 1 other identifier: 2097342
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief Summary

Atherosclerosis is the underlying cause of the majority of cardiovascular diseases, including myocardial infarction and strokes, and results in tremendous morbidity and mortality. A Western-type diet is a major risk factor for atherosclerosis because of the high saturated fat, cholesterol, and refined carbohydrate contents. Dietary strategies to reduce cardiovascular disease burden therefore focus on restriction of saturated fat, cholesterol, and refined carbohydrates whereas "lean" protein intake is recommended and has become popular. However, results from studies conducted in animal models suggest high dietary protein intake is also atherogenic. The investigators' extensive preliminary data in animal models show that dietary protein increases atherosclerotic plaque formation and size and promotes necrotic core formation, a characteristic of rupture-prone plaques. The goal of the current proposal is to provide deeper insights into the relationship between protein intake and the pathogenesis of atherosclerosis by studying the mechanisms involved in protein-mediated atherogenesis and formation of necrotic plaques. The overarching hypothesis is that high protein intake drives atherosclerosis via leucine-mediated mTORC1 signaling in macrophages, which inhibits macrophage mitophagy and aggrephagy and stimulates macrophage proliferation. Furthermore, the investigators hypothesize that proteins from animal sources are more atherogenic than proteins from plant sources, because animal proteins contain more leucine than plant proteins. The investigators will test these hypotheses by using a sophisticated array of experimental strategies, including assays in primary macrophages and human monocyte-derived macrophages and genetically engineered mouse models. In addition, they will begin to translate the results obtained in vitro and in animals to people, and explore approaches to pharmacologically target the pro-atherogenic pathways as novel cardiovascular therapeutics. This proposal represents a paradigm shift in how a Western-type diet affects vascular health which has important implications since many adults in Western societies consume excess protein and dietary protein is heavily marketed for its presumed beneficial health effects.

Conditions

Atherosclerosis

Outcome Measures

Primary Outcomes (1)

• Monocyte p-S6 content

  phospho-S6 content in monocytes

  change from at 1 hour before meal intake and 3 hours after the meal

Study Arms (4)

Standard meal

ACTIVE COMPARATOR

Other: Standard meal

High animal protein meal

EXPERIMENTAL

Other: High animal protein meal

High plant protein meal

EXPERIMENTAL

Other: High plant protein meal

High plant protein meal with additional leucine

EXPERIMENTAL

Other: High plant protein meal with additional leucine

Interventions

Standard meal OTHER

Standard meal

Standard meal

High animal protein meal OTHER

Meal with high animal protein content

High animal protein meal

High plant protein meal OTHER

Meal with high plant protein content

High plant protein meal

High plant protein meal with additional leucine OTHER

Meal with high plant protein content and additional leucine

High plant protein meal with additional leucine

Eligibility Criteria

• Age: 45 Years - 75 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• \>=45 and \<=75 years of age
• body mass index \>=25.0 and \<40.0 kg/m2

You may not qualify if:

• \<45 and \>75 years of age
• body mass index \<25.0 or \>39.9 kg/m2
• plasma triglyceride \<125 mg/dl
• history of or current significant organ system dysfunction
• allergies or intolerances to meal ingredients
• use of medications or dietary supplements that could confound the study outcomes
• engaged in regular structured exercise \>150 min per week
• alcohol use disorder
• premenopausal women
• persons who smoke
• prisoners
• inability to grant voluntary informed consent

Sponsors & Collaborators

• University of Missouri-Columbia: lead

Study Sites (1)

University of Missouri School of Medicine

Columbia, Missouri, 65212, United States

RECRUITING

MeSH Terms

Conditions

Atherosclerosis

Condition Hierarchy (Ancestors)

Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases; Cardiovascular Diseases

Study Officials

• Bettina Mittendorfer

  University of Missouri-Columbia

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Bettina Mittendorfer, PhD

CONTACT

6186103465; b.mittendorfer@missouri.edu

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, OUTCOMES ASSESSOR
• Purpose: OTHER
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Senior Associate Dean for Research

Model Details: Randomized cross-over study

Study Record Dates

• First Submitted: January 18, 2022
• First Posted: February 11, 2022
• Study Start: March 13, 2023
• Primary Completion (Estimated): March 31, 2027
• Study Completion (Estimated): March 31, 2028
• Last Updated: March 17, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)