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

Sponsor

University of Copenhagen (Other)

Overall Status

Recruiting

CT.gov ID

NCT05368194

Collaborator

Deakin University (Other), Monash Health (Other)

Enrollment

Location

Arms

62.4

Anticipated Duration (Months)

0.6

Patients Per Site Per Month

Study Details

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	N/A

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

Anticipated Enrollment :

40 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 :

Oct 20, 2021

Anticipated Primary Completion Date :

Jul 1, 2022

Anticipated Study Completion Date :

Dec 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.

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

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

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
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.
Height [3 weeks]
Measured in meters using a stadiometer (Charder HM-200P Portstad)
Weight [3 weeks]
Measured in kilograms using a scale (Tanita DC 430 SMA)
Body Mass Index (BMI) [3 weeks]
Calculated based on height and weight measurement using the equation BMI=kg/m^2
Waist Circumference [3 weeks]
Measured in centimetres using a flexible measuring tape (SECA Measuring Tape 201 cm)
Hip Circumference [3 weeks]
Measured in centimetres using a flexible measuring tape (SECA Measuring Tape 201 cm)
Body Fat Precentage [3 weeks]
Measured using DEXA Scanner and Software (GE Lunar Prodigy)
C-reactive protein (CRP) [3 weeks]
Measured in milligrams per litre in serum
Lipoproteins [3 weeks]
Measuring high density lipoproteins and low density lipoproteins in milligrams per litre in plasma
Total protein [3 weeks]
Measured in grams per litre in serum
Testosterone [3 weeks]
Measured in nanograms per deciliter in plasma
Follicle stimulating hormone (FSH) [3 weeks]
Measured in international units per milliliter in serum
Luteinizing hormone (LH) [3 weeks]
Measured in international units per liters in plasma
Progesterone [3 weeks]
Measured in nanograms per milliliter in serum
Estradiol [3 weeks]
Measured in picograms per milliliter in serum
Oestradiol [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)
Insulin [3 weeks]
Measured in microunits per milliliter in serum
Haemoglobin A1c (HbA1c) [3 weeks]
Measured in mmol/mol 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)
Leptin [3 weeks]
Measured in ng/mL in plasma
Adiponectin [3 weeks]
Measured in μg/mL in serum
Glucagon-like peptide 1 (GLP-1) [3 weeks]
Measured in pmol/L in plasma
Gastric inhibitory peptide (GIP) [3 weeks]
Measured in pg/mL in serum
Glucagon [3 weeks]
Measured in pg/mL in serum
Ghrelin [3 weeks]
Measured in pg/mL in plasma
Peptide YY (PYY) [3 weeks]
Measured in ng/L in plasma
Fibroblast growth factor 21 (FGF-21) [3 weeks]
Measured in pg/ml in serum
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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

20 Years to 35 Years

Sexes Eligible for Study:

Male

Accepts Healthy Volunteers:

Yes

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

	Site	City	State	Country	Postal Code
1	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

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

University of Copenhagen

ClinicalTrials.gov Identifier:

NCT05368194

Other Study ID Numbers:

H-20061598

First Posted:

May 10, 2022

Last Update Posted:

May 10, 2022

Last Verified:

Oct 1, 2021

Individual Participant Data (IPD) Sharing Statement:

Plan to Share IPD:

Studies a U.S. FDA-regulated Drug Product:

Studies a U.S. FDA-regulated Device Product:

Additional relevant MeSH terms:

Infertility

Overnutrition

Study Results

No Results Posted as of May 10, 2022