Highly Processed Foods and Vascular Health

Cardiovascular Diseases Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05628350
• Other study ID #: 22-819
• Status: Recruiting
• Phase: N/A
• Start date: July 19, 2023
• Est. completion date: July 2025

Study information

• Verified date: April 2024
• Source: Virginia Polytechnic Institute and State University
• Contact: Kevin Davy, PhD
• Phone: 540-231-3487
• Email: kdavy[@]vt.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 42
• Est. completion date: July 2025
• Est. primary completion date: April 2025
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 40 Years to 65 Years

Eligibility

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

Related Conditions & MeSH terms

• Cardiovascular Diseases

Intervention

Other:
• No UPF controlled diet
Following a two-week eucaloric lead-in diet, participants will be provided and consume a diet without UPF (0% energy). Diets will be eucaloric (50% carbohydrate, 35% fat,15% protein), 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, for 6 weeks.
• Standard UPF controlled diet
Following a two-week eucaloric lead-in diet, participants will be provided and consume a diet maintaining usual UPF intake (59% energy). Diets will be eucaloric (50% carbohydrate, 35% fat, 15% protein), 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, for 6 weeks.

Locations

Country	Name	City	State
United States	Virginia Polytechnic and State University	Blacksburg	Virginia

Sponsors (2)

Lead Sponsor	Collaborator
Virginia Polytechnic Institute and State University	Duke University

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Change in insulin sensitivity from baseline to 6-weeks post no or standard 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 standard UPF diet)
Other	Change in 24-hour glucose control (24-hour mean) from baseline to 6-weeks post no or standard 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 standard UPF diet)
Other	Change in 24-hour glucose control (AUC) from baseline to 6-weeks post no or standard 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 standard UPF diet)
Other	Change in 24-hour glucose control (time in range) from baseline to 6-weeks post no or standard 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 standard UPF diet)
Other	Change in 24-hour glucose control (glycemic variability [GV]) from baseline to 6-weeks post no or standard 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 standard UPF diet)
Other	Change in 24-hour glucose control (postprandial glucose) from baseline to 6-weeks post no or standard 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 standard UPF diet)
Primary	Change in brachial artery function from baseline to 6-weeks post no or standard 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 standard UPF diet)
Secondary	Change in arterial stiffness (Carotid femoral pulse wave velocity) from baseline to 6-weeks post no or standard 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 standard UPF diet)
Secondary	Change in arterial stiffness (Beta-stiffness index) from baseline to 6-weeks post no or standard UPF diet	Beta-stiffness index will be measured using high resolution ultrasonography and tonometry of the carotid artery.	45-minute measurement in the laboratory, 2 timepoints (baseline, 6 weeks post no or standard UPF diet)
Secondary	Change in gut microbial composition from baseline to post 6-weeks no or standard 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 standard UPF diet)
Secondary	Change in gut microbial function from baseline to post 6-weeks no or standard 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 standard UPF diet)
Secondary	Change in intestinal inflammation from baseline to post 6-weeks no or standard 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 standard UPF diet)
Secondary	Change in intestinal permeability from baseline to post 6-weeks no or standard 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 standard UPF diet)
Secondary	Change in inflammatory cytokines from baseline to post 6-weeks no or standard 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 standard UPF diet)
Secondary	Change in endotoxin from baseline to post 6-weeks no or standard 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 standard UPF diet)