Diet-Induced Changes in GEnetic Material

Diet, Healthy Clinical Trial

— DIG 'EM  

Official title:

A Pilot Study to Examine Metabolic Flexibility as a Mechanism for Diet- Induced Epigenetic Alterations in Male Gametes

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06252922
• Other study ID #: PBRC 2023-043
• Status: Recruiting
• Start date: November 11, 2023
• Est. completion date: October 3, 2024

Study information

• Verified date: February 2024
• Source: Pennington Biomedical Research Center
• Contact: Emily Flanagan, PhD
• Phone: (225) 763-2828
• Email: Emily.Flanagan[@]pbrc.edu
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

This is a pilot study in 10 men to test the hypothesis that perturbations in substrate flux and the circulating metabolic and pro-inflammatory milieus during a high-fat diet paradigm will modulate DNA methylation of genes in sperm associated with obesity and cardiometabolic dysfunction.

Description:

The Paternal Origins of Health and Disease (POHaD) hypothesis was introduced to emphasize the need for research on paternal transmission of environmental exposures on offspring disease development. Paternal exposure to an obesogenic diet has been shown to imprint epigenetic predisposition to metabolic diseases which can be evident in offspring for up to 5 generations. In support, observational studies in men show that high-fat diets and diets high in processed foods significantly reduced the quantity and quality of sperm, including motility, morphology, and concentration, and DNA methylation of genes associated with obesity and cardiometabolic dysfunction. Yet, there are no experimental diet manipulation studies in males to understand the contribution of an acute obesogenic diet (i.e., high-fat) on DNA methylation of genes associated with obesity and cardiometabolic diseases in male gametes.

The research aims of this study are to: 1) measure DNA methylation of genes in semen in response to a healthy and high-fat diet, 2) examine metabolic flexibility in response to a healthy and high fat diet and its contribution to DNA methylation in semen, and 3) examine the metabolic and inflammatory milieu in response to a healthy and high fat diet and its contribution to DNA methylation in semen. To achieve these aims, we will conduct a cross-sectional, observational study in 10 healthy male participants 20-35 years of age using two diets (Healthy Diet: 27% Fat, 55% Carbohydrate, 15% Protein followed by a High-Fat Diet: 50% Fat, 35% Carbohydrate, 15% Protein).

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 10
• Est. completion date: October 3, 2024
• Est. primary completion date: October 3, 2024
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Male
• Age group: 20 Years to 35 Years

Eligibility

Inclusion Criteria:

• Male based on biological sex

• Age 20-35 years

• BMI between 18.5 and 24.9 kg/m2

• White/Caucasian

• Willing to consume pre-prepared meals

• Willing to wear an accelerometer and continuous glucose monitor (CGM)

• Willing to track diet intake

• Willing to stay 24 hours, including overnight in a research clinic

• Willing to provide blood and sperm samples

• Willing to consent to whole-genome sequencing of DNA

Exclusion Criteria:

• Unstable weight in the last 3 months (±5% weight loss or gain)

• Shift work or working in a factory setting

• Habitual smoking or use of tobacco products, including vaping, within the past 6 months.

• History of clinically diagnosed diabetes

• Hypertension (>140/90 mmHg measured at screening)

• Has undergone bariatric surgery

• History of cardiovascular disease, neurological disease, or other chronic diseases, including cancer

• History of human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS)

• Adherence to special or restrained diets (e.g., low-CHO, low-fat, or vegetarian/vegan diets) or food allergies associated with study foods.

• Currently engaging in >150 minutes moderate-intensity or >75 minutes of vigorous-intensity physical activity each week

• Drinking more than 14 servings of beer or alcohol per week

• Depressive (Score =10), anxiety (Score =8), and stress (Score=15) symptomology (Score =16) from the 42-item Depression, Anxiety, Stress Scales (DASS)

Related Conditions & MeSH terms

• Body Weight
• Diet, Healthy
• Metabolic Disturbance

Locations

Country	Name	City	State
United States	Pennington Biomedical Research Center	Baton Rouge	Louisiana

Sponsors (1)

Lead Sponsor	Collaborator
Pennington Biomedical Research Center

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Metabolic Flexibility (indirect)	Change in respiratory quotient (RQ) from a fasted to a fed state using a metabolic chamber.	Immediately after the healthy diet, Immediately after the high-fat diet
Other	Metabolic Flexibility (direct)	Changes to circulating glucose from a fasted (0 minutes) to a fed state (240 minutes).	Immediately after the healthy diet, Immediately after the high-fat diet
Other	Continuous glucose monitoring	Mean Amplitude of Glycemic Excursions (MAGE) in response to healthy and high fat diets.	Immediately after the healthy diet, Immediately after the high-fat diet
Other	Insulin sensitivity	Mean 24hr glucose and total 24hr c-peptide excretion	Immediately after the healthy diet, Immediately after the high-fat diet
Primary	Sperm DNA methylation	Incidence of DNA methylation (whole genome/epigenome wide) of genes in sperm measured using bisulphate sequencing	Baseline, Immediately after the healthy diet, Immediately after the high-fat diet
Secondary	Sperm DNA Damage	Comet Assay to determine DNA fragmentation in sperm.	Baseline, Immediately after the healthy diet, Immediately after the high-fat diet

External Links

•   Official Study Landing Page