Food Intake and Epigenetic Alteration in the Spermatozoa of Singletons and Twins

Not Applicable

Completed

• Conditions: Fertility Issues; Nutrition, Healthy; Epigenetic Disorder; Overnutrition
• Interventions: Dietary Supplement: Isocaloric Unprocessed Diet; Dietary Supplement: Excess Calorie Unprocessed Diet; Dietary Supplement: Isocaloric Processed Diet; Dietary Supplement: Excess Calorie Processed Diet

• Registration Number: NCT05368194
• Lead Sponsor: University of Copenhagen

Brief Summary

The purpose of this study is to elucidate the role of acute dietary intake in male populations, and its impact on spermatozoa quality, integrity, content and epigenetic programming.

Detailed Description

The FEASST study has been designed to determine the impact of diet on the content, quality, and genetic programming of sperm. They are specifically interested in determining if a man's diet plays a role in influencing the health of his potential, future offspring through modifications of the sperm. Previous research has highlighted that certain dietary patterns in fathers-to-be may lead to variable health outcome for their children. However, the specific effect of a man's diet has yet to be fully understood. This study will help understand the impact of a man's diet on semen quality and potential downstream implications for child health, to aid in the development of dietary guidelines for future fathers-to-be.

For this study, male participants will be provided with two prescribed diets for three-week increments punctuated by a three month break. Health information and biological samples such as blood, semen, and saliva will be collected from study participants throughout the five month period. The diets will consist of a 'Processed diet', mimicking a traditional Western dietary intake pattern and an 'Unprocessed diet', based upon current dietary guidelines at quantities either adequate for the participants energetic needs or 500 calories in excess per day.

Patient information and samples will be collected before and after each dietary intervention. Aspects of patient health examined at various time points include weight, body fat percentage, sperm quality, epigenetic sequencing, serum levels of metabolic parameters, and survey information surrounding health history, typical diet, physical activity patterns, and treatment adherence.

Basic Information
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Recruitment & Eligibility
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Study & Design
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Trial Locations

Study Timeline

• Study Start: 2021-10-20
• Study First Submitted: 2021-12-16
• Study First Submitted QC: 2022-05-09
• Study First Posted: 2022-05-10
• Primary Completion: 2022-07-01
• Study Completion: 2022-07-01
• Status Verified: 2023-12
• Last Update Submitted: 2023-12-06
• Last Update Posted: 2023-12-13

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Male
• Target Recruitment: 43

Inclusion Criteria

• Male
• 20 to 35 years old
• BMI 18.5 to 30
• Located within the Copenhagen region
• Fluent in English and/or Danish language
• Sperm concentration of >15 mil/mL according to the WHO's criteria for semen quality
• Semen volume of >1.5mL mL according to the WHO's criteria for semen quality
• Clinician approval for participation in study
• Obtained informed consent

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Exclusion Criteria

• Self-reported history of serious or chronic illness

• Self-reported history of Obesity

• History of any food restrictions

• History of allergies to any food products

• History of disordered eating

• Record of current use of drugs, alcohol (>14 units per week and/or chronic binge drinking), and/or tobacco/nicotine products within the past month

• Current use of prescription medication

• Engage in > 200 minutes of vigorous aerobic exercise per week

• Currently actively trying to conceive a child

• Diagnosis of infertility or disease of the reproductive system

• Evidence of dysregulated metabolism, characterized by the occurrence of any one of the following:

  • Waist circumference >102 cm
  • Blood pressure > 130/85 mm Hg

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Isocaloric Arm	Isocaloric Unprocessed Diet	Participants within the isocaloric arm will be provided with food provisions in accordance with their nutrition needs. Participants within this arm will be further randomised to the order of first and second dietary interventions for the crossover design; unprocessed diet or processed diet.
Isocaloric Arm	Isocaloric Processed Diet	Participants within the isocaloric arm will be provided with food provisions in accordance with their nutrition needs. Participants within this arm will be further randomised to the order of first and second dietary interventions for the crossover design; unprocessed diet or processed diet.
Excess Calorie Arm	Excess Calorie Unprocessed Diet	Participants within the excess calorie arm will be provided with food provisions in accordance with their nutrition needs plus an additional 500 kilocalories per day. Participants within this arm will be further randomised to the order of first and second dietary interventions for the crossover design; unprocessed diet or processed diet.
Excess Calorie Arm	Excess Calorie Processed Diet	Participants within the excess calorie arm will be provided with food provisions in accordance with their nutrition needs plus an additional 500 kilocalories per day. Participants within this arm will be further randomised to the order of first and second dietary interventions for the crossover design; unprocessed diet or processed diet.

Primary Outcome Measures

Name	Time	Method
Spermatozoa DNA Methylation via Reduced Representation Bisulfite Sequencing	3 weeks	Differential methylation of CpG sites within mature spermatozoa determined from extracted genomic DNA which has undergone library preperation with Ovation® RRBS Methyl-Seq (NuGEN Technologies) and sequenced on a NextSeq Illumina platform.

Secondary Outcome Measures

Name	Time	Method
C-reactive protein (CRP)	3 weeks	Measured in milligrams per litre in serum
Follicle stimulating hormone (FSH)	3 weeks	Measured in international units per milliliter in serum
Body Mass Index (BMI)	3 weeks	Calculated based on height and weight measurement using the equation BMI=kg/m\^2
Hip Circumference	3 weeks	Measured in centimetres using a flexible measuring tape (SECA Measuring Tape 201 cm)
Testosterone	3 weeks	Measured in nanograms per deciliter in plasma
Leptin	3 weeks	Measured in ng/mL in plasma
Gastric inhibitory peptide (GIP)	3 weeks	Measured in pg/mL in serum
Glucagon	3 weeks	Measured in pg/mL in serum
Sperm Concentration	3 weeks	Measured in million sperm per mL using LensHooke X1 Pro Semen Quality Analyser and Microscopy-based methodology
Semen Volume	3 weeks	Measured in mL assuming the density of semen to be 1 g/ml
Sperm Motility	3 weeks	Measured in precent of sperm classified as progressively motile and non-progressively motile using LensHooke X1 Pro Semen Quality Analyser and Microscopy-based methodology
Weight	3 weeks	Measured in kilograms using a scale (Tanita DC 430 SMA)
Body Fat Precentage	3 weeks	Measured using DEXA Scanner and Software (GE Lunar Prodigy)
Total protein	3 weeks	Measured in grams per litre in serum
Progesterone	3 weeks	Measured in nanograms per milliliter in serum
Estradiol	3 weeks	Measured in picograms per milliliter in serum
Fasting Blood Glucose	3 weeks	Measured in whole blood using a handheld glucometer and test strip (Contour next Blood Glucose Meter and Blood Sugar Test strip)
Spermatozoa smallRNA expression via sequencing of total smallRNA species	3 weeks	Differential expression of small RNA species within mature spermatozoa performed by generation of RNA sequencing libraries using NEXTFLEX® Small RNA-Seq Kit for Illumina (PerkinElmer), according to the manufacturer's instructions, and sequenced on a NextSeq Illumina platform.
Lipoproteins	3 weeks	Measuring high density lipoproteins and low density lipoproteins in milligrams per litre in plasma
Insulin	3 weeks	Measured in microunits per milliliter in serum
Haemoglobin A1c (HbA1c)	3 weeks	Measured in mmol/mol in plasma
Waist Circumference	3 weeks	Measured in centimetres using a flexible measuring tape (SECA Measuring Tape 201 cm)
Oestradiol	3 weeks	Measured in picograms per milliliter in serum
Ghrelin	3 weeks	Measured in pg/mL in plasma
Peripheral blood mononuclear cell (PBMC) DNA methylation via Reduced Representation Bisulfite Sequencing	3 weeks	Differential methylation of CpG sites within PBMCs determined from extracted genomic DNA which has undergone library preperation with Ovation® RRBS Methyl-Seq (NuGEN Technologies) and sequenced on a NextSeq Illumina platform.
Luteinizing hormone (LH)	3 weeks	Measured in international units per liters in plasma
Blood pressure	3 weeks	Systolic and Diastolic blood pressure measured in mmHg using an automatic blood pressure cuff (Omron M6 Comfort Automatic Upper Arm Blood Pressure Monitor, 22-42cm)
Glucagon-like peptide 1 (GLP-1)	3 weeks	Measured in pmol/L in plasma
Fibroblast growth factor 21 (FGF-21)	3 weeks	Measured in pg/ml in serum

Trial Locations

Locations (1)

University of Copenhagen; 🇩🇰 Copenhagen, Denmark