Highly Processed Foods and Vascular Health

January 20, 2026 updated by: Kevin Davy, Virginia Polytechnic Institute and State University

Reducing Highly Processed Foods to Improve Vascular Health in Middle-Aged Adults

Age is the primary risk factor for cardiovascular disease (CVD) and age-related vascular dysfunction is considered the key process linking the two. Middle age is a particularly vulnerable period when risk factors exceed diagnostic thresholds and clinical expression of CVD first becomes evident. Ultra-processed foods (UPF) comprise almost 60% of total energy in the standard American diet. The results of observational studies suggest that UPF consumption increases CVD risk, independent of overall diet quality (i.e., saturated fat, sodium, sugar, and dietary fiber intake). The "industrialized microbiota" may link diet, particularly UPF, to increased inflammation and CVD in middle-aged adults. High intake of UPF increases the likelihood of an excess heart age >10 years and doubles the risk of subclinical coronary atherosclerosis in middle-aged adults. However, the impact of reducing UPF consumption on vascular function in middle-aged adults is unknown. The overall objective of this study is to establish proof-of-concept for an improvement in vascular function following reductions in UPF consumption in mid-life adults, in order to conduct a larger, more comprehensive and mechanistic trial in the future. In addition, changes in gut microbial composition and function, intestinal inflammation and permeability, serum endotoxin concentrations, and inflammatory cytokines as potential mechanisms by which UPF consumption influences vascular function will be investigated.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
17

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.
  • Name: Elaina Marinik, PhD
  • Phone Number: 540-231-0923
  • Email: emarinik@vt.edu

Study Contact Backup

  • Name: Kevin Davy, PhD
  • Phone Number: 540-231-3487
  • Email: kdavy@vt.edu

Study Locations

  • United States
    • Virginia
      • Blacksburg, Virginia, United States, 24061
        • Virginia Polytechnic and State University

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

45 years to 65 years (Adult, Older Adult)

Accepts Healthy Volunteers

Yes

Description

Inclusion Criteria:

  • Weight stable for previous 6 months (<2 kg change)
  • Sedentary to recreationally active
  • No plans to gain/lose weight or change physical activity level
  • Willing to pick up food daily and consume foods provided for an 8-week period
  • Verbal and written informed consent
  • Approval by Medical Director
  • Usual UPF intake +/-15% of US average of 60% total energy
  • Estrogen or testosterone usage is acceptable, if on stable dose for >6 months
  • Lipid-lowering medication usage is acceptable, if on a stable dose for >6 months

Exclusion Criteria:

  • BMI >35 kg/m2
  • Diabetes or diabetes medication
  • Antibiotic, prebiotic or prebiotic use in prior 3 months
  • Total Cholesterol >6.2 mmol/L; Triglycerides >4.5 mmol/L
  • Blood pressure (BP) > 159/99 mmHg (Stable BP on antihypertensive medications is acceptable)
  • Diagnosed inflammatory bowel disease
  • Past or current heart diseases, stroke, respiratory disease, endocrine or metabolic disease, or hematological-oncological disease
  • Vegetarian or vegan
  • Pregnant or plans to become pregnant
  • Food allergies or aversions
  • 3 or fewer stools per week or regular laxative use
  • Lipid-lowering medication usage <6 months

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Single

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: No UPF (Ultra-processed foods)
Following a 2-week eucaloric lead-in diet, participants will be provided and consume a diet without UPF (0% total energy) for 6 weeks.
Other: No UPF controlled diet
Following a two-week eucaloric lead-in diet, participants will be provided and consume a diet without UPF (0% total energy) for 6 weeks. Diets will be eucaloric (50% carbohydrate, 35% fat, 15% protein) and matched for dietary soluble and insoluble fiber, added sugar, mono- and polyunsaturated fat, saturated fat, antioxidant nutrients, sodium, pre- and probiotics, and overall diet quality.
Experimental: High UPF
Following a 2-week eucaloric lead-in diet, participants will be provided and consume a diet composed of 81% UPF for 6 weeks.
Other: High UPF controlled diet
Following a two-week eucaloric lead-in diet, participants will be provided and consume a diet with high UPF intake (81% total energy) for 6 weeks. Diets will be eucaloric (50% carbohydrate, 35% fat, 15% protein) and matched for dietary soluble and insoluble fiber, added sugar, mono- and polyunsaturated fat, saturated fat, antioxidant nutrients, sodium, pre- and probiotics, and overall diet quality.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Change in brachial artery function from baseline to 6-weeks post no or high UPF diet
Time Frame: 30-minute measurement in the laboratory, 2 timepoints (baseline, 6 weeks post no or high UPF diet)
Flow Mediated Dilation (FMD) of the brachial artery will be assessed using duplex ultrasonography (GE Logiq e) with a high-resolution linear array transducer. Reactive hyperemia will be produced by inflation of a pediatric BP cuff around the forearm for 5 minutes. Offline analysis of baseline and post-reactive hyperemic diameters and velocities will be performed using edge detection software (Vascular Analysis Tools, Medical Imaging Applications, Inc). Endothelium independent vasodilation (EID) will be assessed by measuring brachial arterial dilation for 10 minutes following administration of 0.4 mg of sublingual nitroglycerine. Both FMD and EID will be expressed as mm and % change from baseline diameter.
30-minute measurement in the laboratory, 2 timepoints (baseline, 6 weeks post no or high UPF diet)

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Change in arterial stiffness (Carotid femoral pulse wave velocity) from baseline to 6-weeks post no or high UPF diet
Time Frame: 45-minute measurement in the laboratory, 2 timepoints (baseline, 6 weeks post no or high UPF diet)
Carotid femoral (C-F) pulse wave velocity (PWV), the primary measure of arterial stiffness, will be measured. C-F waveforms will be obtained via tonometry (NIHem, Cardiovascular Engineering, Inc). Aortic PWV will be calculated from signal averaged waveforms using the ECG as the fiducial point, and body surface measurements.
45-minute measurement in the laboratory, 2 timepoints (baseline, 6 weeks post no or high UPF diet)
Change in gut microbial composition from baseline to post 6-weeks no or high UPF diet
Time Frame: 3-day collection during free-living, 2 timepoints (baseline, 6 weeks post no or high UPF diet)
Stool samples will be collected daily for 3 days before and during the final 3 days of the diet interventions. Samples will be collected daily and placed in sterile plastic containers, stored in personal freezers, and placed in coolers for transport. Upon return to the lab, they will be immediately frozen at -80°C until final processing and analysis.
3-day collection during free-living, 2 timepoints (baseline, 6 weeks post no or high UPF diet)
Change in gut microbial function from baseline to post 6-weeks no or high UPF diet
Time Frame: 3-day collection during free-living, 2 timepoints (baseline, 6 weeks post no or high UPF diet)
Stool samples will be collected daily for 3 days before and during the final 3 days of the diet interventions. Samples will be collected daily and placed in sterile plastic containers, stored in personal freezers, and placed in coolers for transport. Upon return to the lab, they will be immediately frozen at -80°C until final processing and analysis.
3-day collection during free-living, 2 timepoints (baseline, 6 weeks post no or high UPF diet)
Change in intestinal inflammation from baseline to post 6-weeks no or high UPF diet
Time Frame: 3-day collection during free-living, 2 timepoints (baseline, 6 weeks post no or high UPF diet)
Intestinal inflammation will be assessed using fecal calprotectin, lactoferrin, and lipocalin-2, measured using ELISA.
3-day collection during free-living, 2 timepoints (baseline, 6 weeks post no or high UPF diet)
Change in intestinal permeability from baseline to post 6-weeks no or high UPF diet
Time Frame: 3-day collection during free-living, 2 timepoints (baseline, 6 weeks post no or high UPF diet)
Intestinal permeability will be assessed using serum zonulin (Immunodiagnostik AG, Bensheim, Germany) concentrations, measured using ELISA.
3-day collection during free-living, 2 timepoints (baseline, 6 weeks post no or high UPF diet)
Change in inflammatory cytokines from baseline to post 6-weeks no or high UPF diet
Time Frame: 5-minute blood collection in the laboratory, 2 timepoints (baseline, 6 weeks post no or high UPF diet)
Inflammatory cytokines, including Tumor Necrosis Factor alpha, Interleukin 6, and Monocyte Chemoattractant Protein-1, will be measured using ELISA (American Diagnostica Inc).
5-minute blood collection in the laboratory, 2 timepoints (baseline, 6 weeks post no or high UPF diet)
Change in endotoxin from baseline to post 6-weeks no or high UPF diet
Time Frame: 5-minute blood collection in the laboratory, 2 timepoints (baseline, 6 weeks post no or high UPF diet)
Serum endotoxin will be assessed using the PyroGene Recombinant Factor C endotoxin assay (Lonza, Basel, Switzerland).
5-minute blood collection in the laboratory, 2 timepoints (baseline, 6 weeks post no or high UPF diet)

Other Outcome Measures

Other Outcome Measures

For clinical trials, a planned measurement described in the protocol that is used to determine the effect of an intervention/treatment on participants. For observational studies, a measurement or observation that is used to describe patterns of diseases or traits, or associations with exposures, risk factors, or treatment. Types of outcome measures include primary outcome measure and secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Change in insulin sensitivity from baseline to 6-weeks post no or high UPF diet
Time Frame: 2-hour test in laboratory, 2 timepoints (baseline, 6-weeks post no or high UPF diet)
Insulin sensitivity assessed using a 2-hour oral glucose tolerance test (75g glucose load). Blood will be collected at baseline (fasting), and thereafter, at 30-minute intervals (5 total measurements in 2 hours).
2-hour test in laboratory, 2 timepoints (baseline, 6-weeks post no or high UPF diet)
Change in 24-hour glucose control (24-hour mean) from baseline to 6-weeks post no or high UPF diet
Time Frame: 6-day measurement during free-living, 2 timepoints (baseline, 6 weeks post no or high UPF diet)
24-hour glucose control (24-hour mean glucose concentration) will be assessed using continuous glucose monitoring for a 6-day period.
6-day measurement during free-living, 2 timepoints (baseline, 6 weeks post no or high UPF diet)
Change in 24-hour glucose control (AUC) from baseline to 6-weeks post no or high UPF diet
Time Frame: 6-day measurement during free-living, 2 timepoints (baseline, 6 weeks post no or high UPF diet)
24-hour glucose control (24-hour AUC) will be assessed using continuous glucose monitoring for a 6-day period.
6-day measurement during free-living, 2 timepoints (baseline, 6 weeks post no or high UPF diet)
Change in 24-hour glucose control (time in range) from baseline to 6-weeks post no or high UPF diet
Time Frame: 6-day measurement during free-living, 2 timepoints (baseline, 6 weeks post no or high UPF diet)
24-hour glucose control (time in range) will be assessed using continuous glucose monitoring for a 6-day period.
6-day measurement during free-living, 2 timepoints (baseline, 6 weeks post no or high UPF diet)
Change in 24-hour glucose control (glycemic variability [GV]) from baseline to 6-weeks post no or high UPF diet
Time Frame: 6-day measurement during free-living, 2 timepoints (baseline, 6 weeks post no or high UPF diet)
24-hour glucose control (GV) will be assessed using continuous glucose monitoring for a 6-day period.
6-day measurement during free-living, 2 timepoints (baseline, 6 weeks post no or high UPF diet)
Change in 24-hour glucose control (postprandial glucose) from baseline to 6-weeks post no or high UPF diet
Time Frame: 6-day measurement during free-living, 2 timepoints (baseline, 6 weeks post no or high UPF diet)
Free-living postprandial glucose concentration will be assessed using continuous glucose monitoring for a 6-day period.
6-day measurement during free-living, 2 timepoints (baseline, 6 weeks post no or high UPF diet)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Virginia Polytechnic Institute and State University

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Duke University

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Kevin Davy, PhD, Virginia Polytechnic Institute and State University

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
July 19, 2023

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
December 18, 2024

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
September 30, 2025

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
November 16, 2022

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
November 16, 2022

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
November 28, 2022

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
January 22, 2026

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
January 20, 2026

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
January 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 22-819

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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