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Dietary Protein and Monocyte/Macrophage Mammalian Target of Rapamycin (mTOR) Signaling (mTOR)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03946774
Recruitment Status : Suspended (Temporarily paused due to COVID-19 and expected to resume. This is not a suspension of IRB approval.)
First Posted : May 13, 2019
Last Update Posted : May 27, 2020
Sponsor:
Information provided by (Responsible Party):
Washington University School of Medicine

Tracking Information
First Submitted Date  ICMJE March 12, 2019
First Posted Date  ICMJE May 13, 2019
Last Update Posted Date May 27, 2020
Actual Study Start Date  ICMJE January 22, 2019
Estimated Primary Completion Date December 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 12, 2020)
Determination of amino acid levels and mTOR activation in circulating monocytes isolated from subjects ingesting high vs low protein drinks. [ Time Frame: 0 Hour, 1 Hour, and 3 Hours ]
Changes in amino acid levels and corresponding changes in mTOR activation will be quantified at baseline (time 0 hour prior to ingestion of a protein shake), then at 1 and 3 hours after ingestion of a protein shake.
Original Primary Outcome Measures  ICMJE
 (submitted: May 8, 2019)
Determination of amino acid levels and mTOR activation in circulating monocytes isolated from subjects ingesting high vs low protein drinks. [ Time Frame: 0 Hour, 1 Hour, and 4 Hours ]
Changes in amino acid levels and corresponding changes in mTOR activation will be quantified at baseline (time 0 hour prior to ingestion of a protein shake), then at 1 and 4 hours after ingestion of a protein shake.
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: May 12, 2020)
  • Determination of changes in autophagy and apoptosis markers in circulating monocytes over time after ingestion of a protein shake [ Time Frame: 0 Hour, 1 Hour and 3 Hours ]
    Blood collected at three different time points (0, 1 and 3 hours) will be used to measure changes in markers of autophagy and apoptosis at baseline (time 0 hour prior to ingestion of a protein shake), then at 1 and 3 hours after ingestion of a protein shake.
  • Determination of changes in reactive oxygen species in circulating monocytes over time after ingestion of a protein shake. [ Time Frame: 0 Hour, 1 Hour, and 3 Hours ]
    Blood collected at three different time points (0, 1 and 3 hours) will be used to measure changes in levels of reactive oxygen species at baseline (time 0 hour prior to ingestion of a protein shake), then at 1 and 3 hours after ingestion of a protein shake.
  • Determination of changes in inflammatory markers in circulating monocytes over time after ingestion of a protein shake. [ Time Frame: 0 Hour, 1 Hour, and 3 Hours ]
    Blood collected at three different time points (0, 1 and 3 hours) will be used to measure changes in cytokines at baseline (time 0 hour prior to ingestion of a protein shake), then at 1 and 3 hours after ingestion of a protein shake.
Original Secondary Outcome Measures  ICMJE
 (submitted: May 8, 2019)
  • Determination of changes in autophagy and apoptosis markers in circulating monocytes over time after ingestion of a protein shake [ Time Frame: 0 Hour, 1 Hour and 4 Hours ]
    Blood collected at three different time points (0, 1 and 4 hours) will be used to measure changes in markers of autophagy and apoptosis at baseline (time 0 hour prior to ingestion of a protein shake), then at 1 and 4 hours after ingestion of a protein shake.
  • Determination of changes in reactive oxygen species in circulating monocytes over time after ingestion of a protein shake. [ Time Frame: 0 Hour, 1 Hour, and 4 Hours ]
    Blood collected at three different time points (0, 1 and 4 hours) will be used to measure changes in levels of reactive oxygen species at baseline (time 0 hour prior to ingestion of a protein shake), then at 1 and 4 hours after ingestion of a protein shake.
  • Determination of changes in inflammatory markers in circulating monocytes over time after ingestion of a protein shake. [ Time Frame: 0 Hour, 1 Hour, and 4 Hours ]
    Blood collected at three different time points (0, 1 and 4 hours) will be used to measure changes in cytokines at baseline (time 0 hour prior to ingestion of a protein shake), then at 1 and 4 hours after ingestion of a protein shake.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Dietary Protein and Monocyte/Macrophage Mammalian Target of Rapamycin (mTOR) Signaling
Official Title  ICMJE Acute Effects of Dietary Protein on Monocyte/Macrophage mTOR Signaling and Downstream Sequela
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.

The investigators propose to administer high and low protein shakes to participants and measure effects on circulating monocytes, immune cells critical to the development of atherosclerosis and cardiovascular disease. In order to study circulating monocytes, blood will be collected from the study participants just prior to drinking the shake, and then 1 and 4 hours after drinking the shake.

In order to assess functional effects on monocytes, investigators will perform a series of assays comparing the results between individuals who drank high protein vs low protein shakes.

Detailed Description

Cardiovascular disease remains the leading cause of death globally with obesity as of one of the dominant modifiable risk factors. Obesity is also a precursor to several other cardiovascular risk factors including hypertension, hyperlipidemia, and diabetes. Almost all weight loss efforts utilize dietary modification with high protein/low carbohydrate diets serving as one of the most popular approaches. Despite the metabolic benefits of high dietary protein, recent studies have raised a concerning association with increased risk of atherosclerosis and cardiovascular disease. Although this remains controversial, there is some animal data showing evidence of dietary protein's proatherogenic role. These data are correlative and no mechanistic studies have been undertaken.

The downstream events after protein ingestion involve digestion of the protein into amino acids, increases in blood amino acids, and distribution to target tissues. Mouse models have definitively shown that circulating monocytes and macrophages of arterial blood vessels are particularly sensitive to this amino acid load with robust activation of the mTOR (mammalian target of rapamycin) signaling pathway. This in turn leads to inhibition of essential degradative processes of the macrophage such as autophagy and promotes release of pro-inflammatory cytokines. Thus, macrophage function in vascular beds becomes pathogenic leading to atherogenesis and cardiovascular disease

The translation of these mechanistic studies in animal models to human is the next obvious step in this research. However, no studies have elucidated the mechanisms of monocyte activation and function following administration of high dietary protein in humans. The investigators propose a pilot study to bridge an important gap in translational research which will elucidate the mechanisms by which dietary protein affects human monocyte function and the risk of atherosclerotic plaque formation. Specifically, the investigators will evaluate the acute activation of mTOR signaling and downstream sequelae in circulating monocytes following the administration of protein shakes. This study will address the hypothesis that humans exposed to high dietary protein will have significantly higher post-prandial monocyte mTOR activation with concomitant development of impaired degradative capacity and a proinflammatory state.

An understanding of these mechanisms has broad implications in the evaluation and future therapeutic interventions of cardiovascular disease.

In addition, this can provide a valuable clinical tool for health care providers in educating patients on dietary changes to ameliorate cardiovascular risk.

Study Type  ICMJE Interventional
Study Phase  ICMJE Not Applicable
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)
Primary Purpose: Basic Science
Condition  ICMJE Dietary Protein
Intervention  ICMJE Dietary Supplement: Dietary protein shake

It is a milk based protein shake. Ingredients include a combination of the following depending on protein content: Boost Plus (a commercial supplement), Unjury (a commercial whey protein isolate), nonfat dry milk powder, Sol Carb (commercial supplement composed of a carbohydrate polymer), canola oil, and water.

In order to ensure consistency across all participants each beverage will be prepared in the Clinical Translational Research Unit Metabolic Kitchen under the supervision of a registered dietitian prior to the study participant's visit. Ingredients are individually weighed on a food scale by metabolic kitchen staff to the nearest 0.1 g and then mixed using a magnetic stir plate.

Nutritional breakdown of the smoothies (high versus low protein):

High protein drink nutrition: 500 kcal per serving, 50% protein, 17% fat, and 36% carbohydrate.

Low (standard) protein drink nutrition: 500 kcal per serving, 10% protein, 17% fat, and 73% carbohydrate.

Study Arms  ICMJE
  • Active Comparator: High protein
    Subjects getting high protein shake
    Intervention: Dietary Supplement: Dietary protein shake
  • Active Comparator: Low protein
    Subjects getting low protein shake
    Intervention: Dietary Supplement: Dietary protein shake
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Suspended
Estimated Enrollment  ICMJE
 (submitted: May 8, 2019)
20
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE December 2020
Estimated Primary Completion Date December 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. 18+ years of age
  2. Able to drink milk based protein shake

Exclusion Criteria:

  1. Current Pregnancy
  2. Any food allergies
  3. Personal Hx of Diabetes
  4. Personal Hx of Heart Disease
  5. Personal Hx of High blood pressure
  6. Personal Hx of Stroke
  7. Personal Hx of Cancer
  8. Personal Hx of Organ transplant
  9. Taking Rapamycin/Sirolimus
  10. Taking Torisel/Temsirolimus
  11. Taking Afinitor/Everolimus
  12. Taking any statin medication (eg.simvastatin/atorvastatin/rosuvastatin etc)
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03946774
Other Study ID Numbers  ICMJE 201808084
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Washington University School of Medicine
Study Sponsor  ICMJE Washington University School of Medicine
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account Washington University School of Medicine
Verification Date May 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP