Food Intake and Epigenetic Alteration in the Spermatozoa of Singletons and Twins (FEASST)

• ClinicalTrials.gov Identifier: NCT05368194
• Recruitment Status: Active, not recruiting
• First Posted: May 10, 2022
• Last Update Posted: November 3, 2022
• Sponsor: University of Copenhagen
• Collaborators: Deakin University; Monash Health
• Information provided by (Responsible Party): University of Copenhagen

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Fertility Issues; Nutrition, Healthy; Epigenetic Disorder; Overnutrition	Dietary Supplement: Isocaloric Unprocessed Diet; Dietary Supplement: Isocaloric Processed Diet; Dietary Supplement: Excess Calorie Unprocessed Diet; Dietary Supplement: Excess Calorie Processed Diet	Not Applicable

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 43 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Double (Participant, Outcomes Assessor)
• Primary Purpose: Basic Science
• Official Title: The FEASST Study: Food Intake and Epigenetic Alteration in the Spermatozoa of Singletons and Twins
• Actual Study Start Date: October 20, 2021
• Actual Primary Completion Date: July 1, 2022
• Estimated Study Completion Date: December 31, 2026

Arms and Interventions

Arm	Intervention/treatment
Experimental: Isocaloric Arm; 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.	Dietary Supplement: Isocaloric Unprocessed Diet; Intervention consists of an unprocessed diet meeting the Nordic and Australian Dietary Guidelines for food groups and micronutrients, wherein participants will be supplied with food providing kilocalories (kcal) in accordance with their nutritional needs as calculated based on theSchofield equation based on their weight, activity multiplier, and age at baseline. Almost all food and beverage products provided during this treatment to fall into the category of unprocessed/minimally processed foods and processed culinary ingredients in accordance with the NOVA classification system.; Dietary Supplement: Isocaloric Processed Diet; Intervention consists of a processed diet based on the dietary intake pattern resembling a processed western dietary intake pattern representative of the typical intake pattern of American men aged 19- 50, wherein participants will be supplied with food providing kcals in accordance with their nutritional needs as calculated based on the Schofield equation based on their height, weight, activity multiplier, and age at baseline. Almost all food and beverage products provided during this treatment to fall into the category of processed foods and ultra-processed foods in accordance with the NOVA classification system.
Experimental: Excess Calorie Arm; 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.	Dietary Supplement: Excess Calorie Unprocessed Diet; Intervention consists of an unprocessed diet meeting the Nordic and Australian Dietary Guidelines for food groups and micronutrients, wherein participants will be supplied with food providing kilocalories (kcal) in accordance with their nutritional needs as calculated based on theSchofield equation based on their weight, activity multiplier, and age at baseline, plus an excess of 500 kcal per day. Almost all food and beverage products provided during this treatment to fall into the category of unprocessed/minimally processed foods and processed culinary ingredients in accordance with the NOVA classification system.; Dietary Supplement: Excess Calorie Processed Diet; Intervention consists of a processed diet based on the dietary intake pattern resembling a processed western dietary intake pattern representative of the typical intake pattern of American men aged 19- 50, wherein participants will be supplied with food providing kcals in accordance with their nutritional needs as calculated based on the Schofield equation based on their height, weight, activity multiplier, and age at baseline, plus an excess of 500 kcal per day. Almost all food and beverage products provided during this treatment to fall into the category of processed foods and ultra-processed foods in accordance with the NOVA classification system.

Outcome Measures

Primary Outcome Measures :

1. Spermatozoa DNA Methylation via Reduced Representation Bisulfite Sequencing [ Time Frame: 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 :

1. Sperm Concentration [ Time Frame: 3 weeks ]
   Measured in million sperm per mL using LensHooke X1 Pro Semen Quality Analyser and Microscopy-based methodology
2. Semen Volume [ Time Frame: 3 weeks ]
   Measured in mL assuming the density of semen to be 1 g/ml
3. Sperm Motility [ Time Frame: 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
4. Spermatozoa smallRNA expression via sequencing of total smallRNA species [ Time Frame: 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.
5. Height [ Time Frame: 3 weeks ]
   Measured in meters using a stadiometer (Charder HM-200P Portstad)
6. Weight [ Time Frame: 3 weeks ]
   Measured in kilograms using a scale (Tanita DC 430 SMA)
7. Body Mass Index (BMI) [ Time Frame: 3 weeks ]
   Calculated based on height and weight measurement using the equation BMI=kg/m^2
8. Waist Circumference [ Time Frame: 3 weeks ]
   Measured in centimetres using a flexible measuring tape (SECA Measuring Tape 201 cm)
9. Hip Circumference [ Time Frame: 3 weeks ]
   Measured in centimetres using a flexible measuring tape (SECA Measuring Tape 201 cm)
10. Body Fat Precentage [ Time Frame: 3 weeks ]
    Measured using DEXA Scanner and Software (GE Lunar Prodigy)
11. C-reactive protein (CRP) [ Time Frame: 3 weeks ]
    Measured in milligrams per litre in serum
12. Lipoproteins [ Time Frame: 3 weeks ]
    Measuring high density lipoproteins and low density lipoproteins in milligrams per litre in plasma
13. Total protein [ Time Frame: 3 weeks ]
    Measured in grams per litre in serum
14. Testosterone [ Time Frame: 3 weeks ]
    Measured in nanograms per deciliter in plasma
15. Follicle stimulating hormone (FSH) [ Time Frame: 3 weeks ]
    Measured in international units per milliliter in serum
16. Luteinizing hormone (LH) [ Time Frame: 3 weeks ]
    Measured in international units per liters in plasma
17. Progesterone [ Time Frame: 3 weeks ]
    Measured in nanograms per milliliter in serum
18. Estradiol [ Time Frame: 3 weeks ]
    Measured in picograms per milliliter in serum
19. Oestradiol [ Time Frame: 3 weeks ]
    Measured in picograms per milliliter in serum
20. Fasting Blood Glucose [ Time Frame: 3 weeks ]
    Measured in whole blood using a handheld glucometer and test strip (Contour next Blood Glucose Meter and Blood Sugar Test strip)
21. Insulin [ Time Frame: 3 weeks ]
    Measured in microunits per milliliter in serum
22. Haemoglobin A1c (HbA1c) [ Time Frame: 3 weeks ]
    Measured in mmol/mol in plasma
23. Blood pressure [ Time Frame: 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)
24. Leptin [ Time Frame: 3 weeks ]
    Measured in ng/mL in plasma
25. Adiponectin [ Time Frame: 3 weeks ]
    Measured in μg/mL in serum
26. Glucagon-like peptide 1 (GLP-1) [ Time Frame: 3 weeks ]
    Measured in pmol/L in plasma
27. Gastric inhibitory peptide (GIP) [ Time Frame: 3 weeks ]
    Measured in pg/mL in serum
28. Glucagon [ Time Frame: 3 weeks ]
    Measured in pg/mL in serum
29. Ghrelin [ Time Frame: 3 weeks ]
    Measured in pg/mL in plasma
30. Peptide YY (PYY) [ Time Frame: 3 weeks ]
    Measured in ng/L in plasma
31. Fibroblast growth factor 21 (FGF-21) [ Time Frame: 3 weeks ]
    Measured in pg/ml in serum
32. Peripheral blood mononuclear cell (PBMC) DNA methylation via Reduced Representation Bisulfite Sequencing [ Time Frame: 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.

Eligibility Criteria

• Ages Eligible for Study: 20 Years to 35 Years (Adult)
• Sexes Eligible for Study: Male
• Accepts Healthy Volunteers: Yes

Criteria

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

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

Contacts and Locations

Locations

Denmark

University of Copenhagen

Copenhagen, Denmark, 2200

Sponsors and Collaborators

University of Copenhagen

Deakin University

Monash Health

Investigators

• Principal Investigator: Romain Barrès, PhD; University of Copenhagen Novo Nordisk Foundation Center for Basic Metabolic Research

More Information

• Responsible Party: University of Copenhagen
• ClinicalTrials.gov Identifier: NCT05368194
• Other Study ID Numbers: H-20061598
• First Posted: May 10, 2022
• Last Update Posted: November 3, 2022
• Last Verified: November 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Infertility; Overnutrition; Nutrition Disorders