Leucine, MTOR and Athero

NCT05470218 | Active Not Recruiting

• 1 other identifier: HPL
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief Summary

High protein low carbohydrate diets have become popular in recent years to help facilitate weight loss. It is controversial if these diets are associated with an increased risk of cardiovascular disease. Recent work in mice has implicated monocytes/macrophages and mTOR signaling as the culprit cell type driving the increased cardiovascular risk with high protein diets. We aim to build on this preclinical research by evaluating the effects of liquid meals with different protein and leucine (a potent mTOR activator) contents on circulating human monocytes and platelets. Study participants will be given either a low protein liquid meal, a high protein liquid meal, or a low protein liquid meal with additional leucine. Blood will be collected from study participants just just prior to and for several hours after ingestion of the meals. Activation of amino acid-dependent signaling pathways (particularly mTOR) and downstream sequelae will be evaluated in the isolated monocytes and platelets.

Conditions

Atherosclerosis

Outcome Measures

Primary Outcomes (1)

• p-mTOR in monocytes

  change from before meal at 1 hour and 3 hours, compared to before

Study Arms (3)

Standard protein meal

ACTIVE COMPARATOR

Participants will receive a standard protein meal, containing about 10% of energy as protein

Other: Meal

High protein meal

ACTIVE COMPARATOR

Participants will receive a high protein meal, containing about 50% of energy as protein

Other: Meal

Low protein meal + leucine

ACTIVE COMPARATOR

Participants will receive a standard protein meal, containing about 10% of energy as protein to which leucine has been added to match the total leucine content of the high protein meal

Other: Meal

Interventions

Meal OTHER

Liquid mixed meal with different amounts of protein and leucine

High protein meal; Low protein meal + leucine; Standard protein meal

Eligibility Criteria

• Age: 18 Years - 95 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• years or older
• able to drink milk-based liquid mixed meal

You may not qualify if:

• Current Pregnancy
• Allergies to meal ingredients
• History of Diabetes
• History of Heart Disease
• History of High blood pressure
• History of Stroke
• History of Cancer
• History of Organ transplant
• Taking Rapamycin/Sirolimus
• Taking Torisel/Temsirolimus
• Taking Afinitor/Everolimus
• Taking any statin medication

Sponsors & Collaborators

• University of Missouri-Columbia: lead
• Washington University School of Medicine: collaborator

Study Sites (1)

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

MeSH Terms

Conditions

Atherosclerosis

Interventions

Meals

Condition Hierarchy (Ancestors)

Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Food; Diet, Food, and Nutrition; Physiological Phenomena; Food and Beverages

Study Officials

• Bettina Mittendorfer

  University of Missouri-Columbia

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Medicine

Model Details: Single-group crossover

Study Record Dates

• First Submitted: July 13, 2022
• First Posted: July 22, 2022
• Study Start: July 12, 2022
• Primary Completion: August 14, 2023
• Study Completion (Estimated): August 14, 2026
• Last Updated: March 17, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL
• Time Frame: beginning 12 months and ending 36 months following article publication

Locations

US (1)