Project 1: Diet and Exercise Modulate the Sperm Epigenome in Men

Summary

This is a rigorous, controlled clinical trial designed to show that diet, exercise training, and their combination in overweight, inactive men will alter epigenetic programming to create a "healthy" sperm epigenome. Our central hypotheses are: i) overweight and inactive lifestyle results in epimutations in the sperm epigenome relative to the normal epigenetic programming in lean and active men and ii) diet and exercise modulation leads to reversal of these epimutations resulting in both a healthier "phenotype" and "epigenotype" which may persist after stopping the interventions. The study is divided into three parts:

1. We will recruit 20 healthy, active men and 20 obese and inactive Hispanic men between 18 and 40 years to determine the differences in sperm epigenome (DNA methylation, histone modifications and non-coding RNAs) in a cross-sectional study in obese inactive vs. healthy active Hispanic men. Only Hispanic men will be studied because of the high prevalence of obesity and inactivity in Hispanic younger men and to reduce the genetic variability influencing the epigenome.
2. 80 obese and inactive men will be randomized to 4 groups of 20 men: 1) No intervention (control); 2) Low fat, low caloric diet; 3) Supervised, periodized endurance and resistance training without modification of diet; and 4) Both exercise and diet modification to characterize the plasticity of the sperm epigenome in response to 12-week diet and/or exercise training interventions in obese and inactive Hispanic men. Sperm epimutations will be compared before and after intervention within each group and between groups.
3. The sperm epigenome studies in 80 men randomized to no intervention or diet and/or exercise training will be repeated at 12 and 36 weeks after cessation of interventions to Identify the persistent effects of diet and exercise training on the sperm epigenome after stopping the interventions.

Conditions

• Healthy Lifestyle
• Obese
• Men

Interventions

OTHER

Diet

Participants will receive delivered meals every 4 weeks for three months of a variety of foods for breakfast, lunch, dinner, two snacks, and an additional snack or dessert for each day.

OTHER

Exercise

Training will be supervised, individualized, and periodized, incorporating 3 sessions per week, 45-60 min per session for 36 sessions.

OTHER

Standard care

Observational

Sponsors & Collaborators

• Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

  collaborator NIH

• Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center

  lead OTHER

Principal Investigators

• Christina Wang, MD · The Lundquist Institute

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

PARALLEL

Eligibility

Min Age

18 Years

Max Age

40 Years

Sex

MALE

Healthy Volunteers

Yes

Timeline & Regulatory

Start

2020-02-21

Primary Completion

2025-09-03

Completion

2026-06-30

Countries

• United States

Study Locations