AtherosclerosisHPANCT05235464
High Protein Diet and Atherosclerosis
A study testing Standard meal, High animal protein meal and High plant protein meal in people with Atherosclerosis, run by University of Missouri-Columbia at 1 site in United States.
Trial summary
Atherosclerosis is the underlying cause of the majority of cardiovascular diseases, including myocardial infarction and strokes, and results in tremendous morbidity and mortality. Read more about this study
- Who is it for?
- Ages 45 to 75 yearsHealthy volunteers can take part
- Conditions the study is for
- Atherosclerosis
- What is being tested?
- Standard meal, High animal protein meal and High plant protein meal
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 24 participants
- Where
- 1 siteUnited States
- Study dates
- 13 Mar 2023to 31 Mar 2028
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 45 to 75 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- >=45 and <=75 years of age
- body mass index >=25.0 and <40.0 kg/m2
Who cannot join
- <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
Show all 12Show fewer
- engaged in regular structured exercise >150 min per week
- alcohol use disorder
- premenopausal women
- persons who smoke
- prisoners
- inability to grant voluntary informed consent
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
University of Missouri School of Medicine
Columbia, Missouri, 65212
Vasavi Shabrish, v.shabrish@missouri.edu
About this study
Official title: Dissecting the Impact of Dietary Protein on Macrophage mTOR Signaling and Atherosclerosis
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
- Being tested
- Standard meal, High animal protein meal, High plant protein meal, High plant protein meal with additional leucine
- Medical subject headings
- Atherosclerosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Standard mealOther
Standard meal
High animal protein mealOther
Meal with high animal protein content
High plant protein mealOther
Meal with high plant protein content
High plant protein meal with additional leucineOther
Meal with high plant protein content and additional leucine
| Study group | Role | What they receive |
|---|---|---|
| Standard meal | Active comparator | Not described Receives: Other: Standard meal |
| High animal protein meal | Experimental | Not described Receives: Other: High animal protein meal |
| High plant protein meal | Experimental | Not described Receives: Other: High plant protein meal |
| High plant protein meal with additional leucine | Experimental | Not described Receives: Other: High plant protein meal with additional leucine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Monocyte proatherogenic pathway activation
Change in proatherogenic pathway activation
Measured: baseline before meal intake to 3 hours after the meal
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Feb 2022
- Study start13 Mar 2023
- Primary completion31 Mar 2027 (estimated)
- Study completion31 Mar 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for AtherosclerosisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Crossover
- Model description
- Randomized cross-over study
- Masking
- Double blind
- Who is masked
- Participant, Outcomes assessor
- Enrolment
- 24 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Missouri-Columbia
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Bettina Mittendorfer, University of Missouri-Columbia
- Investigators
- Bettina Mittendorfer, Principal investigator, University of Missouri-Columbia
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05235464
- Sponsor's protocol ID
- 2097342
- Acronym
- HPA
- Status last verified
- Apr 2026
- First submitted
- 18 Jan 2022
- Last updated
- 11 May 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Fappi A, Shabrish V, Hollomon H, Islam T, Zhang X, Razani B, Klein S, Mittendorfer B. High animal protein and high plant protein meals differentially alter postprandial plasma amino acid concentrations but not glucose homeostasis in people with overweight/obesity in a randomized, cross-over, single-meal study. Am J Clin Nutr. 2026 Aug 10:101468. doi: 10.1016/j.ajcnut.2026.101468. Online ahead of print.
PubMed 42575285
Study at a glance
From the registry record, last updated by the sponsor on 11 May 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Dissecting the Impact of Dietary Protein on Macrophage mTOR Signaling and Atherosclerosis
- ClinicalTrials.gov ID
- NCT05235464
- Acronym / sponsor ID
- HPA / 2097342
- Conditions
- Atherosclerosis
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 24 participants (estimated)
- Lead sponsor
- University of Missouri-ColumbiaUniversity, hospital or other
- Study start
- 13 Mar 2023 (actual)
- Primary completion
- 31 Mar 2027 (estimated)
- Study completion
- 31 Mar 2028 (estimated)
- First posted
- 11 Feb 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind (participant, outcomes assessor)
- Number of arms
- 4
- Model description
- Randomized cross-over study
| Arm | Type | Receives |
|---|---|---|
| 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 |
Who may qualify
- Ages
- 45 to 75 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- >=45 and <=75 years of age
- body mass index >=25.0 and <40.0 kg/m2
Key exclusion criteria (12 listed)
- <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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Standard mealStandard meal | Other | Standard meal |
| High animal protein mealMeal with high animal protein content | Other | High animal protein meal |
| High plant protein mealMeal with high plant protein content | Other | High plant protein meal |
| High plant protein meal with additional leucineMeal with high plant protein content and additional leucine | Other | High plant protein meal with additional leucine |
Primary outcome
Monocyte proatherogenic pathway activation
Time frame: baseline before meal intake to 3 hours after the meal
Change in proatherogenic pathway activation
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 May 2026.
- Derived from this study: PubMed 42575285Fappi A, Shabrish V, Hollomon H, Islam T, Zhang X, Razani B, Klein S, Mittendorfer B. High animal protein and high plant protein meals differentially alter postprandial plasma amino acid concentrations but not glucose homeostasis in people with overweight/obesity in a randomized, cross-over, single-meal study. Am J Clin Nutr. 2026 Aug 10:101468. doi: 10.1016/j.ajcnut.2026.101468. Online ahead of print.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Bettina Mittendorfer principal investigator
University of Missouri-Columbia
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Standard meal, High animal protein meal and High plant protein meal in people with Atherosclerosis, run by University of Missouri-Columbia at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 11 May 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Bettina Mittendorfer, PhD (6186103465, b.mittendorfer@missouri.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Monocyte proatherogenic pathway activation (time frame: baseline before meal intake to 3 hours after the meal). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05235464, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 May 2026; AzTrials last refreshed its copy on 31 Oct 2026.