Leucine, mTOR and Athero (HPL)

Protein, Platelet, and Monocyte

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Atherosclerosis
• Intervention / Treatment: Other: Meal

• Study Type: Interventional
• Enrollment (Estimated): 10
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Missouri
    • St Louis, Missouri, United States, 63110
      • Washington University School of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 95 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

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

Exclusion Criteria:

• 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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Standard protein meal; Participants will receive a standard protein meal, containing about 10% of energy as protein	Other: Meal; Liquid mixed meal with different amounts of protein and leucine
Active Comparator: High protein meal; Participants will receive a high protein meal, containing about 50% of energy as protein	Other: Meal; Liquid mixed meal with different amounts of protein and leucine
Active Comparator: Low protein meal + leucine; 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; Liquid mixed meal with different amounts of protein and leucine

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
p-mTOR in monocytes	change from before meal at 1 hour and 3 hours, compared to before

Collaborators and Investigators

• Sponsor: University of Missouri-Columbia
• Collaborators: Washington University School of Medicine
• Investigators: Principal Investigator: Bettina Mittendorfer, University of Missouri-Columbia

Study record dates

Study Major Dates

• Study Start (Actual): July 12, 2022
• Primary Completion (Actual): August 14, 2023
• Study Completion (Estimated): August 14, 2026

Study Registration Dates

• First Submitted: July 13, 2022
• First Submitted That Met QC Criteria: July 20, 2022
• First Posted (Actual): July 22, 2022

Study Record Updates

• Last Update Posted (Actual): May 11, 2026
• Last Update Submitted That Met QC Criteria: May 5, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Vascular Diseases; Cardiovascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Atherosclerosis; Food; Diet, Food, and Nutrition; Physiological Phenomena; Food and Beverages; Meals
• Other Study ID Numbers: HPL

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: De-identified data will be shared upon reasonable request beginning 12 months and ending 36 months following article publication
• IPD Sharing Time Frame: beginning 12 months and ending 36 months following article publication
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No