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

NCT04175678 | Active Not Recruiting

• 2 other identifiers: 31568-011P50HD098593-01
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 1

Brief 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. 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. 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. 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

Keywords

Hispanic Men; Healthy Men; Obese Men; Exercise; Diet

Outcome Measures

Primary Outcomes (1)

• Changes in the sperm epigenome

  The Primary endpoint is to compare alterations in the sperm epigenome (DNA methylation, histone modifications, non-coding RNAs) in obese, physically inactive men before and following diet modulation and/or exercise training; this will be contrasted to a parallel no intervention group.

  5 years

Secondary Outcomes (5)

• Sperm Epigenetic Signals

  5 years

• Effects of Diet and Exercise Training on the Sperm Epigenome

  5 years

• Effects of Diet or /and Exercise on Phenotypic Features

  5 years

• Analyze persistent effects of diet and/or exercise

  5 years

• Correlate alterations in sperm epigenome with clinical and biochemical fitness biomarkers

  5 years

Study Arms (5)

Normal/Active

ACTIVE COMPARATOR

No intervention

Other: Standard care

Obese/Inactive

PLACEBO COMPARATOR

Observational clinic visits

Other: Standard care

Diet

EXPERIMENTAL

low fat/low caloric diet

Other: Diet

Exercise Training

EXPERIMENTAL

≥3 sessions with fitness trainer per week, for ≥30 min, at moderate to high intensity

Other: Exercise

Diet and exercise training

EXPERIMENTAL

low fat/low caloric diet and ≥3 sessions with fitness trainer per week, for ≥30 min, at moderate to high intensity

Other: Diet; Other: Exercise

Interventions

Diet OTHER

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.

Also known as: low fat/low cal diet

Diet; Diet and exercise training

Exercise OTHER

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

Diet and exercise training; Exercise Training

Standard care OTHER

Observational

Normal/Active; Obese/Inactive

Eligibility Criteria

• Age: 18 Years - 40 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Male volunteers in good health as confirmed by physical examination, medical history, and clinical laboratory tests of blood and urine within the reference range at the time of screening
• Must have Hispanic Father and Mother from Mexico or Central America
• Normal weight, active subjects:
• BMI 18.5 - 24.9 calculated as weight in Kg/ (height in cm)2
• Participates in ≥150 min/week of moderate intensity physical activity as assessed by accelerometer
• Consume \< 30% of calories as fat/day
• Fasting lipid panel within reference range or not clinically significant above the reference ranges
• Obese and physically inactive subjects:
• BMI ≥ 30 calculated as weight in Kg/ (height in cm)2 in obese subjects
• Have risk factors for developing type 2 diabetes (first degree relatives with Diabetes Mellitus type 2, BP≥130/80, HDL-cholesterol ≤ 35mg/dL or triglycerides ≥200mg/dL, fasting plasma glucose ≥100mg/dl to 125mg/dL or HgbA1c ≥ 5.7 to 6.4%, abnormal liver transaminases (not more than 3 times upper limit of normal suggestive of hepatic steatosis)
• Participates in ≤150 min/week of moderate intensity physical activity
• Consume \>30 % fat as calories/day
• Stable weight for past six months prior to the first screening visit
• Willing to commit to 12 weeks of three times a week personalized exercise training
• Willing to commit to 12 weeks of weight loss diet (low fat and low calories)

You may not qualify if:

• Men who meet any of the following criteria are NOT eligible for enrollment in the trial:
• Men participating in another clinical trial within the last 30 days prior to the first screening visit
• Men not living in the catchment's area of the clinic or within a reasonable distance from the site
• Clinically significant abnormal findings at screening except for those stated above for the obese, inactive group
• Sperm concentration below 15 million/mL in more than one of three screening samples
• Diastolic (D) blood pressure (BP) \> 30 and Systolic (S) BP \> 130 mm Hg for the healthy, non-obese and active group; and diastolic (D) blood pressure (BP) \> 150 and Systolic (S) BP \> 100 mm Hg for the obese, inactive group on in the opinion of the investigator not suitable for exercise training (BP will be taken 3 times at 5 minute intervals and the mean of all measurements be considered)
• History of hypertension, including hypertension controlled with treatment in the healthy, active group
• Known history of reproductive dysfunction including vasectomy or infertility
• Known history of cardiac, renal, hepatic, cardiac or respiratory disease
• A serious systemic disease such as diabetes mellitus defined by the American Diabetes Association or morbid obesity (body weight greater than 120% of ideal body weight or BMI limitation as above)
• Known or suspected alcoholism or drug abuse or chronic infections
• Serious digestive and/or absorptive problems, including inflammatory bowel disease and
• Chronic food intolerance or diarrhea that preclude adherence to the study diet.
• Cardiovascular, respiratory or musculoskeletal disease or joint problems that preclude moderate physical activity.
• Psychiatric disorders (including eating disorders) or conditions that, in the opinion of the investigator, would preclude participation in the study intervention (e.g. untreated major depression or psychosis, substance abuse, severe personality disorder).

Sponsors & Collaborators

• Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD): collaborator
• Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center: lead

Study Sites (1)

The Lundquist Institute

Torrance, California, 90502, United States

Location

MeSH Terms

Conditions

Obesity; Multiple Endocrine Neoplasia Type 1; Motor Activity

Interventions

Diet; Exercise; Standard of Care

Condition Hierarchy (Ancestors)

Overweight; Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Multiple Endocrine Neoplasia; Endocrine Gland Neoplasms; Neoplasms by Site; Neoplasms; Neoplasms, Multiple Primary; Neoplastic Syndromes, Hereditary; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Endocrine System Diseases; Behavior

Intervention Hierarchy (Ancestors)

Nutritional Physiological Phenomena; Diet, Food, and Nutrition; Physiological Phenomena; Motor Activity; Movement; Musculoskeletal Physiological Phenomena; Musculoskeletal and Neural Physiological Phenomena; Quality Indicators, Health Care; Quality of Health Care; Health Services Administration; Health Care Quality, Access, and Evaluation

Study Officials

• Christina Wang, MD

  The Lundquist Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: November 21, 2019
• First Posted: November 25, 2019
• Study Start: February 21, 2020
• Primary Completion: September 3, 2025
• Study Completion (Estimated): June 30, 2026
• Last Updated: March 10, 2026

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)