PubertyNCT06690866
Negative Emotionality and Epigenetics During Puberty
An observational study of Puberty and Healthy, run by International Research Training Group 2804 at 1 site in Germany.
Trial summary
Pubertal transition leads to enduring neuroendocrine changes along with changes in the epigenome. The prevalence of psychiatric disorders significantly increases in females compared to males after puberty. Read more about this study
- Who is it for?
- Ages 8 to 17 years, women onlyHealthy volunteers can take part
- What is being tested?
- Stress
- Type of treatment
- Lifestyle or therapy programme
- How many people
- 100 participants
- Where
- 1 siteGermany
- Study dates
- 26 Mar 2024to Apr 2026
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 8 to 17 years
- Women only
- Healthy volunteers accepted
- Child
Study population: Pubescent girls between 8 and 17 years of age living and schooling in Tübingen and surrounding area
Who may be able to join
- healthy girls
- aged between 8-10 and having pubertal stage 1 or between 15-17 and having pubertal stage 5
- normal body mass index according to age (between 5th and 85th percentile)
- non-smoking
- German language fluency
- Attending age-appropriate schools
Who cannot join
- neurological or psychiatric disease
- medical problems such as hormonal, metabolic, developmental or chronic diseases (e.g., congenital disorders, precocious puberty, polycystic ovarian syndrome, diabetes or congestive heart failure)
- any kind of hormonal, pharmacological or psychotropic treatment in the last three months
- engaging in competitive/extreme sports
- Additional exclusion criteria for MRI:
- People with non-removable metal objects on or in the body
Show all 11Show fewer
- Tattoos (if not MRI-incompatible according to expert guidelines)
- Pathological hearing or increased sensitivity to loud noises
- Claustrophobia
- Surgery less than three months ago
- Moderate or severe head injury
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Germany1 site, 1 recruiting
- Recruiting
University of Tuebingen; Department of Psychiatry & Psychotherapy; Tuebingen
Tübingen, Baden-Wurttemberg, 72076
Vanessa Nieratschker, Prof. Dr., +497071 29-85523, vanessa.nieratschker@med.uni-tuebingen.de
Mirac Nur Musaoglu, MD
About this study
Official title: Negative Emotionality in Relation to Epigenetics of Estrogen Signaling During Puberty
Pubertal transition leads to enduring neuroendocrine changes along with changes in the epigenome. The prevalence of psychiatric disorders significantly increases in females compared to males after puberty. There is likely to be an interaction between epigenetics, hormones and neurophysiological processes during puberty, leading to the increased prevalence of mental disorders in females. This study aims to shed light on these interactions underlying the emerging sex differences after puberty. Specifically, it seeks to investigate the epigenetic modifications and subsequent changes in gene expression during the pubertal transition and their association with negative emotionality (e.g., acute stress response and depressive symptoms) at molecular, neuronal, subjective and physiological levels.
Read the detailed description
In order to investigate epigenetic and neuroimaging correlates of negative emotionality in pubertal girls, the study employs a cross-sectional design, enrolling 50 pre-pubescent girls (8-10 years) and 50 post-pubescent girls (15-17 years) as healthy participants. Comprehensive data will be collected using self- and parent-report questionnaires on pubertal status, prenatal complications, adverse life events, stress and coping mechanisms, mood and anxiety symptoms, gender identity, and reproductive health. To delve into the neuronal correlates of stress, participants will undergo (f)MRI and MIST. Additionally, physiological stress responses will be assessed through heart rate and skin conductance measurements. Participants will provide blood, saliva, and hair samples for hormone, methylation and expression analysis. DNA methylation analysis will be performed on whole blood and saliva samples using pyrosequencing, focusing on genes that are responsive to estrogen and genes involved in estrogen signaling, based on the previous literature reporting an overrepresentation of estrogen-responsive genes among the differentially methylated sites across the entire genome in girls during puberty. The effects of methylation on gene expression will be measured using reverse transcription real-time PCR. Cortisol levels will be assessed from saliva collected six times during MIST to evaluate the acute stress response and from hair to assess chronic stress. Sex steroids such as estrogen and progesterone from blood will be analyzed using LC-MS/MS. The study aims to provide insights into the intricate relationship between epigenetic modifications, gene expression and negative emotionality (e.g., stress reactivity and internalizing symptoms) during puberty in girls.
- Being tested
- Stress
- Keywords
- Stress reactivity, DNA methylation, fMRI
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
StressBehavioural
Montreal Imaging Stress Task is a stress paradigm in the scanner to examine neuronal correlates of acute psychosocial stress.
| Study group | Role | What they receive |
|---|---|---|
| Pre-pubertal girls (children) | 8-10 years of girls having pubertal stage 1 Receives: Behavioral: Stress | |
| Post-pubertal girls (adolescents) | 15-17 years of girls having pubertal stage 5 Receives: Behavioral: Stress |
What is being measured
The primary outcome is the main question the study is designed to answer.
DNA methylation differences between pre- and post-pubertal girls in candidate genes
DNA methylation (DNAm) leves in genes involved in estrogen signaling and neuronal estrogen responsive genes in blood and saliva
Measured: Measured once after MRI measurement (approximately 30 minutes).
Correlation between DNA methylation and neuronal activity during acute stress
Neuronal activity during acute stress is determined by the contrast differences between stress and control conditions assessed with task-based fMRI, Montreal Imaging Stress Task (MIST). The correlation between neuronal activity and DNA methylation. Comparing pre- and post-pubescent girls.
Measured: Measured once: 3 runs of MIST lasting 20 minutes in total.
The mediating role of sex steroids in DNA methlation and negative emotionality
The mediating effect of estradiol, progesterone, testosterone and allopregnanolone levels in blood on the correlation between DNA methylation and indicators of negative emotionality (e.g., neuronal activity during stress (MIST task) and mood symptoms). Comparing pre- and post-pubescent girls
Measured: Measured once for each part: 20 minutes for MIST, 30 minutes for blood and saliva collection, and 1 hour for questionnaires
Secondary outcomes (6)
Correlation between DNA methylation and gene expression in candidate genes
The expression levels of genes involved in estrogen signaling and neuronal estrogen responsive genes in blood and saliva with RT-PCR. Correlation between DNA methlaytion and expression.
Measured: Measured once after MRI measurement (approximately 30 minutes)
Correlation between DNA methylation and HPA-axis response
Cortisol levels from saliva samples collected before and after MIST. Correlation between area under the curve (AUC) for cortisol and DNA methylation. Is there a mediating role of DNA methylation on the correlation between HPA-axis reactivity and negative emotionality (e.g., internalizing symptoms and stress processing)? Comparing pre- and post-pubescent girls.
Measured: Measured six times: 1 hour before MIST(1), just before(1) and after(1) MIST, and three times more in 20-minute intervals after MIST. Each saliva collection lasts approx. 2 minutes.
Correlation between DNA methylation and subjective stress response
Correlation between emotional ratings and stress levels assessed with each saliva sample before and after MIST and DNA methylation. Emotional ratings are based on self-assessment mannikin (SAM) which is a non-verbal pictorial tool. Stress levels evaluated with a stress thermometer using a scale of 1-10; 1 indicating not at all, 10 very strong. Is there a mediating effect of DNA methylation on the correlation between subjective stress response and negative emotionality (e.g., internalizing symptoms and stress processing). Comparing pre-and post-pubertal girls
Measured: Measured six times: 1 hour before MIST(1), just before(1) and after(1) MIST, and three times more in 20-minute intervals after MIST. Each rating takes approx. 10 minutes.
Correlation between DNA methylation and phsiological stress response
Correlation between HR, HRV and skin conductance changes during stress task (MIST) and DNA methylation. The interaction between physiological acute stress response and DNA methylation in relation to negative emotionality (e.g., internalizing symptoms and stress processing). Comparing pre-and post-pubertal girls
Measured: Measured once: 20 minutes for phsiological data during MRI measurement
Correlation between DNA methylation and functional connectivity
The correlation between functional connectivity in brain networks (e.g., default mode network (DMN) and salience network (SN)) and DNA methlaytion. The correlation between regions of interest (i.e., amygdala, anterior cingulate cortex, and hippocampus) activity during rest condition and DNA methylation. Is there a mediating role of DNA methylation on the correlation between resting-state neuronal activity and negative emotionality (e.g., mood and anxiety symptoms)? Comparing pre- and post-pubertal girls.
Measured: Measured once with resting-state functional MRI, approximately 10 mintes
Correlation between DNA methylation and brain gray matter structure
The correlation between gray matter volumes obtained from anatomical T1-weighted images in regions of interest (i.e., amygdala, dorsolateral prefrontal cortex, putamen, anterior cingulate, hippocampus, ventral striatum) and DNA methylation. Is there a mediating role of DNA methylation on the correlation between region of interest gray matter volumes and negative emotionality (e.g., stress processing, mood and anxiety symptoms). Comparing pre- and post-pubescent girls.
Measured: Measured once with MPRAGE MRI, approximately 10 minutes. Analyzed and reported over the course of the study, in average of 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Nov 2024
- Study start26 Mar 2024
- Primary completionDec 2025 (estimated)
- Study completionApr 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for PubertyStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Cross-sectional
- Enrolment
- 100 participants (estimated)
Sponsor and investigators
- Lead sponsor
- International Research Training Group 2804
- Sponsor type
- University, hospital or other
- Collaborators
- University Hospital Tuebingen, Uppsala University, German Research Foundation
- Responsible party
- Sponsor
- Investigators
- Vanessa Nieratschker, Prof., Principal investigator, University Hospital TuebingenMirac Nur Musaoglu, MD, Study director, University Hospital Tuebingen
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06690866
- Sponsor's protocol ID
- IRTG_P01
- Status last verified
- Nov 2024
- First submitted
- 8 Nov 2024
- Last updated
- 15 Nov 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: After the publication of the key results of the study, all anonymized imaging data will be made publicly available.
Study at a glance
From the registry record, last updated by the sponsor on 15 Nov 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Negative Emotionality in Relation to Epigenetics of Estrogen Signaling During Puberty
- ClinicalTrials.gov ID
- NCT06690866
- Acronym / sponsor ID
- IRTG_P01
- Keywords
- Stress reactivity, DNA methylation, fMRI
- Study type
- Observational
- Recruitment status
- Recruiting
- Enrolment
- 100 participants (estimated)
- Lead sponsor
- International Research Training Group 2804University, hospital or other
- Collaborators
- University Hospital Tuebingen, Uppsala University, German Research Foundation
- Study start
- 26 Mar 2024 (actual)
- Primary completion
- Dec 2025 (estimated)
- Study completion
- Apr 2026 (estimated)
- First posted
- 15 Nov 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Pubertal transition leads to enduring neuroendocrine changes along with changes in the epigenome. The prevalence of psychiatric disorders significantly increases in females compared to males after puberty. There is likely to be an interaction between epigenetics, hormones and neurophysiological processes during puberty, leading to the increased prevalence of mental disorders in females. This study aims to shed light on these interactions underlying the emerging sex differences after puberty. Specifically, it seeks to investigate the epigenetic modifications and subsequent changes in gene expression during the pubertal transition and their association with negative emotionality (e.g., acute stress response and depressive symptoms) at molecular, neuronal, subjective and physiological levels.
Detailed description
In order to investigate epigenetic and neuroimaging correlates of negative emotionality in pubertal girls, the study employs a cross-sectional design, enrolling 50 pre-pubescent girls (8-10 years) and 50 post-pubescent girls (15-17 years) as healthy participants. Comprehensive data will be collected using self- and parent-report questionnaires on pubertal status, prenatal complications, adverse life events, stress and coping mechanisms, mood and anxiety symptoms, gender identity, and reproductive health. To delve into the neuronal correlates of stress, participants will undergo (f)MRI and MIST. Additionally, physiological stress responses will be assessed through heart rate and skin conductance measurements. Participants will provide blood, saliva, and hair samples for hormone, methylation and expression analysis. DNA methylation analysis will be performed on whole blood and saliva samples using pyrosequencing, focusing on genes that are responsive to estrogen and genes involved in estrogen signaling, based on the previous literature reporting an overrepresentation of estrogen-responsive genes among the differentially methylated sites across the entire genome in girls during puberty. The effects of methylation on gene expression will be measured using reverse transcription real-time PCR. Cortisol levels will be assessed from saliva collected six times during MIST to evaluate the acute stress response and from hair to assess chronic stress. Sex steroids such as estrogen and progesterone from blood will be analyzed using LC-MS/MS. The study aims to provide insights into the intricate relationship between epigenetic modifications, gene expression and negative emotionality (e.g., stress reactivity and internalizing symptoms) during puberty in girls.
Study design
- Observational model
- Cohort
- Time perspective
- Cross-sectional
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Pre-pubertal girls (children) | – | Behavioral: Stress8-10 years of girls having pubertal stage 1 |
| Post-pubertal girls (adolescents) | – | Behavioral: Stress15-17 years of girls having pubertal stage 5 |
Who may qualify
- Ages
- 8 to 17 years
- Sex
- Female only
- Healthy volunteers
- Accepted
- Age groups
- Child
- Study population
- Pubescent girls between 8 and 17 years of age living and schooling in Tübingen and surrounding area
Key inclusion criteria (6 listed)
- healthy girls
- aged between 8-10 and having pubertal stage 1 or between 15-17 and having pubertal stage 5
- normal body mass index according to age (between 5th and 85th percentile)
- non-smoking
- German language fluency
Key exclusion criteria (11 listed)
- neurological or psychiatric disease
- medical problems such as hormonal, metabolic, developmental or chronic diseases (e.g., congenital disorders, precocious puberty, polycystic ovarian syndrome, diabetes or congestive heart failure)
- any kind of hormonal, pharmacological or psychotropic treatment in the last three months
- engaging in competitive/extreme sports
- People with non-removable metal objects on or in the body
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| StressMontreal Imaging Stress Task is a stress paradigm in the scanner to examine neuronal correlates of acute psychosocial stress. | Behavioural | Post-pubertal girls (adolescents), Pre-pubertal girls (children) |
Primary outcome
DNA methylation differences between pre- and post-pubertal girls in candidate genes
Time frame: Measured once after MRI measurement (approximately 30 minutes).
DNA methylation (DNAm) leves in genes involved in estrogen signaling and neuronal estrogen responsive genes in blood and saliva
Correlation between DNA methylation and neuronal activity during acute stress
Time frame: Measured once: 3 runs of MIST lasting 20 minutes in total.
Neuronal activity during acute stress is determined by the contrast differences between stress and control conditions assessed with task-based fMRI, Montreal Imaging Stress Task (MIST). The correlation between neuronal activity and DNA methylation. Comparing pre- and post-pubescent girls.
The mediating role of sex steroids in DNA methlation and negative emotionality
Time frame: Measured once for each part: 20 minutes for MIST, 30 minutes for blood and saliva collection, and 1 hour for questionnaires
The mediating effect of estradiol, progesterone, testosterone and allopregnanolone levels in blood on the correlation between DNA methylation and indicators of negative emotionality (e.g., neuronal activity during stress (MIST task) and mood symptoms). Comparing pre- and post-pubescent girls
6 secondary outcomes
Correlation between DNA methylation and gene expression in candidate genes
Time frame: Measured once after MRI measurement (approximately 30 minutes)
Correlation between DNA methylation and HPA-axis response
Time frame: Measured six times: 1 hour before MIST(1), just before(1) and after(1) MIST, and three times more in 20-minute intervals after MIST. Each saliva collection lasts approx. 2 minutes.
Correlation between DNA methylation and subjective stress response
Time frame: Measured six times: 1 hour before MIST(1), just before(1) and after(1) MIST, and three times more in 20-minute intervals after MIST. Each rating takes approx. 10 minutes.
Correlation between DNA methylation and phsiological stress response
Time frame: Measured once: 20 minutes for phsiological data during MRI measurement
Correlation between DNA methylation and functional connectivity
Time frame: Measured once with resting-state functional MRI, approximately 10 mintes
Correlation between DNA methylation and brain gray matter structure
Time frame: Measured once with MPRAGE MRI, approximately 10 minutes. Analyzed and reported over the course of the study, in average of 1 year
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Nov 2024.
- Individual participant dataSharing planned: Yes. After the publication of the key results of the study, all anonymized imaging data will be made publicly available.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Vanessa Nieratschker, Prof. principal investigator
University Hospital Tuebingen
Mirac Nur Musaoglu, MD study director
University Hospital Tuebingen
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Puberty and Healthy, run by International Research Training Group 2804 at 1 site in Germany.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 15 Nov 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Germany. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Vanessa Nieratschker, Prof. Dr. (+497071-2985523, vanessa.nieratschker@med.uni-tuebingen.de), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
DNA methylation differences between pre- and post-pubertal girls in candidate genes (time frame: Measured once after MRI measurement (approximately 30 minutes).). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Nov 2024.