Ignite Creation Date:
2024-10-26 @ 3:35 PM
Last Modification Date:
2024-10-26 @ 3:35 PM
Study NCT ID:
NCT06509776
Status:
NOT_YET_RECRUITING
Last Update Posted:
None
First Post:
2024-07-15
Brief Title:
Skeletal Maturation and Endocrine Health in Young Adults
Sponsor:
None
Organization:
None
Study Overview
Official Title:
Early Life Determinants of Skeletal Maturation and Endocrine Health in Young Adults - A Nationwide Birth Cohort Study
Status:
NOT_YET_RECRUITING
Status Verified Date:
2024-07
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
No
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
EPIPEAK
Brief Summary:
Diseases which can be the result of poor lifestyle choices in adult life such as osteoporosis obesity or poor muscle mass sarcopenia can also be driven by heritable genetic factors More surprisingly perhaps the genes we inherit from our parents can be modified as a result of influences that affected the health and pregnancy of our mothers and hence the environment experienced in the womb and at birth The purpose of this study is to investigate which factors are needed for good bone health and hormonal health in young adulthood as well as good muscle mass and normal fat mass and how this is influenced by factors before birth and by childhood health Specifically we will measure bone mass and body composition in young adults 18 years of age and measure hormones in blood and in hair samples The clinical visits will be available nationwide at several centers to make participation swift and easy for participants The changes known as epigenetic modification to genes at birth will be studied in dried blood spot samples stored from birth 18 years ago in the Danish Serum Institute and we will use national health registers to identify factors during pregnancy and in childhood that contribute to health effects at age 18
Detailed Description:
Population-based nationwide cross-sectional clinical study with already available early life exposure data including bio banked neonatal biological samples An embedded design using the full 20062007 birth cohorts is used to demonstrate external validity of the clinically assessed cohort We will obtain the necessary ethics and regulatory approval and individual consent from the participants who are all aged 18
The overall aim of the project addresses whether the following sets of potential determinants are associated with young adult hormonal status lipids bone turnover markers bone mineral density BMD fat mass and lean body mass at age 18 years a maternal risk factors during preconception and pregnancy b risk factors at birth c neonatal epigenetic signature d childhood risk factors
Aim 1 - Epigenetics - Is peak bone mass and body size influenced by epigenetic profile for endocrine signals at birth From the second trimester of pregnancy and until early adulthood bone is gradually developed and shaped with longitudinal growth dominating the later stages of fetal life infancy and childhood This is followed by a period of rapid bone mineral accrual occurring up to and during puberty with bone mass accretion ultimately reaching a plateau in young adult life It is strongly suggested by prior research that epigenetic variation at birth can result from differences in maternal health lifestyle nutrition smoking and medication usage and result in long-term changes in gene expression and metabolism
As existing childhood cohorts either lack BMD information suffer from significant cohort attrition and low recruitment success there is an opportunity to instead use national invitations to recruit directly into an efficient endocrine and bone outcomes study and use already archived biological material from early infancy and register data and obtain individual study subject consent
Aim 2 - Endocrine status in young adulthood - Does maternal medication use and health issues prior to pregnancy or in pregnancy affect endocrine health in young adults This question will be addressed using data from Danish national registers While it is straightforward to link binary events data eg malformations or paediatric admissions eg epilepsy diabetes failure to thrive to registry capture of their maternal exposures we will be obtaining detailed information about continuous outcomes including endocrine serum biochemistry thyroid axis GH axis PTH-vitamin D-calcium axis lipids HbA1c hair cortisol levels a cumulative serum cortisol metric as well as body composition and bone density metrics
Aim 3 - DXA measured muscle fat mass and lipid status in young adults - Do suboptimal conditions prior to pregnancy during pregnancy birth and childhood such as lifestyle poor health and low socioeconomics adversely influence establishment of healthy body composition and lipid status in young adulthood Detailed register-based information prior to pregnancy about pregnancy birth and childhood health will be used to identify areas open to prevention Detailed information will be obtained via the Danish national health registers
Statistical consideration - With a study population of 2000 the power given α005 available to detect a 02 SD effect on a continuous outcome such as PBM for a risk factor with a population prevalence of 20 is 90 With inclusion of 1500 subjects the corresponding study power is 90 for detection of an effect size of 024 SD or 80 for detection of an effect size of 02 SD The study needs this resolving power to be able to address multiple contributing factors and for the inclusion of factors in the model that may have a population prevalence below 20 Less common factors would even if powerful drivers of skeletal health be somewhat less useful in population impact even if successfully modified
Biological material - All material for use in the current project will be stored in a research biobank during the current study during its term Any remaining material is transferred to biobank for future research with the approval of the Danish Data Protection Agency The purpose of the biobank is to ensure validation of the analysis methods used over time The participants must give consent to the storage of their biological material in the biobank It is completely optional if the participants want to donate their excess biological material to the biobank and if they do not want this it does not affect their participation in the study For new research new consent must be obtained but the Scientific Ethics Committee can grant exemption from the consent requirement
All material will be stored in compliance with Danish legislation on data protection
24 mL of blood will be drawn All blood samples are encoded so that all samples are anonymized and the key is under special protection and only with access for authorized personnel All extra material will be kept in the biobank
To ensure uniformity between neonatal and adolescent samples DBS will be created from the freshly drawn whole blood DBS are created by spotting 3x75µL onto a cotton filter paper of the same type used in 2006-2007 The cards are left overnight at ambient temperatures then transferred to -20C for long term storage DNA is be extracted from two 32mm disks excised from the DBS card then purified using magnetic silica beads Finally concentrations are measured using intercalating dyes
All hair samples minimum 20 mg per participant will be encoded so that all samples are pseudonymised and the key is under special protection and only with access for authorized personnel All hair samples will be used in the analyses and then discarded
The overall aim of the project addresses whether the following sets of potential determinants are associated with young adult hormonal status lipids bone turnover markers bone mineral density BMD fat mass and lean body mass at age 18 years a maternal risk factors during preconception and pregnancy b risk factors at birth c neonatal epigenetic signature d childhood risk factors
Aim 1 - Epigenetics - Is peak bone mass and body size influenced by epigenetic profile for endocrine signals at birth From the second trimester of pregnancy and until early adulthood bone is gradually developed and shaped with longitudinal growth dominating the later stages of fetal life infancy and childhood This is followed by a period of rapid bone mineral accrual occurring up to and during puberty with bone mass accretion ultimately reaching a plateau in young adult life It is strongly suggested by prior research that epigenetic variation at birth can result from differences in maternal health lifestyle nutrition smoking and medication usage and result in long-term changes in gene expression and metabolism
As existing childhood cohorts either lack BMD information suffer from significant cohort attrition and low recruitment success there is an opportunity to instead use national invitations to recruit directly into an efficient endocrine and bone outcomes study and use already archived biological material from early infancy and register data and obtain individual study subject consent
Aim 2 - Endocrine status in young adulthood - Does maternal medication use and health issues prior to pregnancy or in pregnancy affect endocrine health in young adults This question will be addressed using data from Danish national registers While it is straightforward to link binary events data eg malformations or paediatric admissions eg epilepsy diabetes failure to thrive to registry capture of their maternal exposures we will be obtaining detailed information about continuous outcomes including endocrine serum biochemistry thyroid axis GH axis PTH-vitamin D-calcium axis lipids HbA1c hair cortisol levels a cumulative serum cortisol metric as well as body composition and bone density metrics
Aim 3 - DXA measured muscle fat mass and lipid status in young adults - Do suboptimal conditions prior to pregnancy during pregnancy birth and childhood such as lifestyle poor health and low socioeconomics adversely influence establishment of healthy body composition and lipid status in young adulthood Detailed register-based information prior to pregnancy about pregnancy birth and childhood health will be used to identify areas open to prevention Detailed information will be obtained via the Danish national health registers
Statistical consideration - With a study population of 2000 the power given α005 available to detect a 02 SD effect on a continuous outcome such as PBM for a risk factor with a population prevalence of 20 is 90 With inclusion of 1500 subjects the corresponding study power is 90 for detection of an effect size of 024 SD or 80 for detection of an effect size of 02 SD The study needs this resolving power to be able to address multiple contributing factors and for the inclusion of factors in the model that may have a population prevalence below 20 Less common factors would even if powerful drivers of skeletal health be somewhat less useful in population impact even if successfully modified
Biological material - All material for use in the current project will be stored in a research biobank during the current study during its term Any remaining material is transferred to biobank for future research with the approval of the Danish Data Protection Agency The purpose of the biobank is to ensure validation of the analysis methods used over time The participants must give consent to the storage of their biological material in the biobank It is completely optional if the participants want to donate their excess biological material to the biobank and if they do not want this it does not affect their participation in the study For new research new consent must be obtained but the Scientific Ethics Committee can grant exemption from the consent requirement
All material will be stored in compliance with Danish legislation on data protection
24 mL of blood will be drawn All blood samples are encoded so that all samples are anonymized and the key is under special protection and only with access for authorized personnel All extra material will be kept in the biobank
To ensure uniformity between neonatal and adolescent samples DBS will be created from the freshly drawn whole blood DBS are created by spotting 3x75µL onto a cotton filter paper of the same type used in 2006-2007 The cards are left overnight at ambient temperatures then transferred to -20C for long term storage DNA is be extracted from two 32mm disks excised from the DBS card then purified using magnetic silica beads Finally concentrations are measured using intercalating dyes
All hair samples minimum 20 mg per participant will be encoded so that all samples are pseudonymised and the key is under special protection and only with access for authorized personnel All hair samples will be used in the analyses and then discarded
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None