What side effects are associated with this type of intervention?

Common treatments for atherosclerosis, such as statins and PCSK9 inhibitors, have well-documented side effects. Statins can cause muscle pain, liver enzyme abnormalities, and, in rare cases, rhabdomyolysis. PCSK9 inhibitors, like alirocumab and evolocumab, may cause injection site reactions, hypersensitivity reactions, and, rarely, neurocognitive symptoms. Dietary interventions, particularly those high in protein, may contribute to atherogenesis through mechanisms involving leucine-mediated mTORC1 signaling in macrophages, potentially leading to increased plaque formation and instability.

What prior FDA approvals exist?

FDA-approved treatments for atherosclerosis include statins, which lower cholesterol levels, and PCSK9 inhibitors like evolocumab and alirocumab, which reduce LDL cholesterol. Additionally, mTOR inhibitors such as rapamycin have shown promise in preclinical studies by reducing atherosclerotic plaque progression through mechanisms involving macrophage activity. While rapamycin itself is not specifically approved for atherosclerosis, its effects on mTORC1 signaling are relevant to the ongoing research on high protein intake and atherosclerosis.

What other types of research exist?

Promising alternatives to high protein intake for atherosclerosis patients include: 1) Adopting a diet low in saturated fat, cholesterol, and refined carbohydrates, while emphasizing lean protein sources such as plant-based proteins. 2) Incorporating more fruits, vegetables, legumes, and whole grains into the diet. 3) Using pharmacological interventions that target mTORC1 signaling pathways, such as rapamycin or its analogs, which have shown potential in reducing atherosclerotic plaque formation. 4) Considering statin therapy to manage cholesterol levels and reduce cardiovascular risk.

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High Protein Diet for Atherosclerosis (HPA Trial)

N/A

Recruiting

Led By Bettina Mittendorfer

Research Sponsored by University of Missouri-Columbia

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

>=45 and <=75 years of age

Be older than 18 years old

Must not have

<45 and >75 years of age

inability to grant voluntary informed consent

Timeline

Screening 3 weeks

Treatment Varies

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

Awards & highlights

No Placebo-Only Group

Summary

This trial looks at how eating a lot of protein affects plaque buildup in arteries, which can lead to heart attacks and strokes. It focuses on adults in Western societies who eat a lot of protein. The study suggests that animal proteins might be worse because they interfere with cell cleaning processes, leading to more plaque.

Who is the study for?

This trial is for adults aged 45-75 with a BMI of 25.0 to less than 40.0 kg/m2, who do not smoke and have no significant organ dysfunction or allergies to meal ingredients. It excludes those on certain medications or supplements, highly active individuals, alcohol users with disorders, premenopausal women, prisoners, and anyone unable to consent.

What is being tested?

The study tests the effects of different diets on atherosclerosis: high plant protein meals (with and without extra leucine), standard meals, and high animal protein meals. The focus is on how these diets might influence heart disease by affecting plaque in arteries.

What are the potential side effects?

While specific side effects are not listed for diet interventions like these, participants may experience changes in digestion or energy levels due to dietary adjustments.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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I am between 45 and 75 years old.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I am between 45 and 75 years old.

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I am unable to understand and give voluntary consent for treatment.

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I am a woman who has not gone through menopause.

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I do not have any major organ system problems.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

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

Screening ~ 3 weeks

Treatment ~ Varies

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

This trial's timeline: 3 weeks for screening, Varies for treatment, and change from at 1 hour before meal intake and 3 hours after the meal for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Monocyte p-S6 content

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

4Treatment groups

Experimental Treatment

Active Control

Group I: High plant protein meal with additional leucineExperimental Treatment1 Intervention

Group II: High plant protein mealExperimental Treatment1 Intervention

Group III: High animal protein mealExperimental Treatment1 Intervention

Group IV: Standard mealActive Control1 Intervention

0 / 5Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Common treatments for atherosclerosis often target the pathways involved in plaque formation and progression. For instance, dietary interventions that reduce high-leucine protein intake can mitigate the leucine-mediated mTORC1 signaling in macrophages, which is known to inhibit macrophage mitophagy and aggrephagy, leading to reduced plaque formation. Pharmacological treatments like statins lower cholesterol levels and reduce inflammation, while medications such as rapamycin inhibit mTOR signaling and reduce monocyte chemotaxis, slowing plaque progression. These treatments are vital for atherosclerosis patients as they address the root causes of plaque development, thereby lowering the risk of severe cardiovascular events like heart attacks and strokes.

Rapamycin attenuates atherosclerotic plaque progression in apolipoprotein E knockout mice: inhibitory effect on monocyte chemotaxis.