Trial document




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  DRKS00023288

Trial Description

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Title

Does early-life stress promote protracted neuroinflammation in women? Towards understanding early developmental origins of accelerated brain ageing

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Trial Acronym

StressBrainAge

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URL of the Trial

https://neurocure.de/klinisches-zentrum/forschung-am-ncrc/laufende-studien/stressbrainage-studie.html

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Brief Summary in Lay Language

The aim of our study is to determine the connection between childhood experiences on inflammatory and aging processes in the brain and whether such experiences influence or even promote these processes in the human brain.
People adapt to their environment, including through changes in the human body and brain. This frequently observed phenomenon is particularly pronounced in childhood. Therefore, both positive and negative conditions during early development can have particularly significant and long-lasting effects.
What is done?
- Anamnesis interview, physical examination
- Questionnaire survey and interview about childhood experiences
- Neuropsychological testing
- single blood sampling
- Magnetic Resonance Imaging (MRT)
Participation criteria are:
- Women between 30 - 60 years
- no serious physical, psychiatric or neurological diseases
- no metal parts in and on the body
- no claustrophobia
- no pregnancy

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Brief Summary in Scientific Language

Early childhood stress - Early Life Stress (ELS) - involves exposure to various forms of severe childhood stressors, including maltreatment, abuse, violence, neglect or loss of a parent.
So far, systemic inflammation, accelerated cell aging and activation of immunological processes related to ELS in children and adults could be replicated successfully (Baumeister, Akhtar, Ciufolini, Pariante, & Mondelli, 2016; Idan Shalev et al., 2013). Moreover, animal models and studies in humans have already shown that ELS induces significant changes at the structural and functional level of the neuronal circuits involved in stress, which are mainly involved in adaptation to stress and emotional regulation (Anacker, O'Donnell, & Meaney, 2014; C. Heim & Nemeroff, 2001).
Despite the profound knowledge about systemic inflammation after early aversive life experiences, there is almost no knowledge available to date about how these inflammatory processes affect the brain in adult humans. Results from animal studies suggest that chronic stress increases Aβ mediated neuronal toxicity and leads to increased accumulation of tau protein (Dong & Csernansky, 2009).
Neuroinflammation plays an undisputed role in the pathophysiology of neurodegenerative diseases (Kinney et al., 2018). However, the exact human interaction pattern of triggers such as ELS and inflammation associated with increased susceptibility to neurodegenerative changes remains poorly understood.
The discrepancy between the chronological age of an individual and the predicted age of the brain, calculated using multimodal imaging techniques, could represent a clinically relevant and novel biomarker for this purpose. While previous predictive studies mainly used functional and structural aspects of imaging for this purpose, multimodal imaging will now be used to improve age prediction. Since studies have already shown that ELS experience in later life leads to cognitive dysfunction in adults (Reincke & Hanganu-Opatz, 2017; Saleh et al., 2017), calculating the predicted age of the brain would also be a suitable method for measuring the level of cognitive impairment after ELS.

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Do you plan to share individual participant data with other researchers?

No

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Description IPD sharing plan:

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Organizational Data

  •   DRKS00023288
  •   2020/10/30
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  •   yes
  •   Approved
  •   EA2/085/20, Ethik-Kommission der Charité -Universitätsmedizin Berlin-
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Secondary IDs

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Health Condition or Problem studied

  •   Z61 -  Problems related to negative life events in childhood
  •   Neuroinflammation
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Interventions/Observational Groups

  •   ELS Group - ELS from childhood to menarche recorded through standardized questionnaires (Childhood Trauma Questionnaire and Reactions to Research Participation Questionnaire) and an interview
  •   Control group - exclusion of any ELS recorded through standardized questionnaires (Childhood Trauma Questionnaire and Reactions to Research Participation Questionnaire) and an interview
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Characteristics

  •   Non-interventional
  •   Observational study
  •   Non-randomized controlled trial
  •   Open (masking not used)
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  •   Other
  •   Basic research/physiological study
  •   Parallel
  •   N/A
  •   N/A
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Primary Outcome

1. Markers for neuroinflammation are measured by quantitative multiparameter mapping (MPM); MPM measures microstructural changes such as myelin, iron content and macrophage activity
2. Determination of the calculated brain age using multimodal MRI data to analyze a brain age score including functional and structural connectivity, cortical thickness, cortical surface and subcortical volume in relation to chronological age

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Secondary Outcome

- Neurocognitive functions are determined using standardized neuropsychological testing procedures for cognitive performance
- Quantification of brain metabolites [including NAA, myoinositol, choline, creatine and glutamate using single-voxel 1H-MR spectroscopy in the hippocampus and cinguli posterior gyrus
- Determination of systemic inflammation and senescence markers in venous blood (e.g. IL-6, CRP, TNF-alpha, lymphocyte immunophenotyping, telomer length, mitogenically stimulated telomerase activity, P16INK4a). Additional determination of risk markers in venous blood for neurodegenerative diseases (e.g. Aβ40, Aβ42, neurofilament light protein)
- Standard rating scales will be used to assess depression as a moderator, e.g. Beck Depression Inventory (BDI-II; Hautzinger et al., 2009)

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Countries of Recruitment

  •   Germany
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Locations of Recruitment

  • University Medical Center 
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Recruitment

  •   Actual
  •   2021/03/05
  •   190
  •   Monocenter trial
  •   National
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Inclusion Criteria

  •   Female
  •   30   Years
  •   60   Years
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Additional Inclusion Criteria

- Ability to give consent
- Legally effective, written declaration of consent to participate in the study
- Existing health insurance to clarify possible random findings, Additional inclusion criteria ELS-group
- ELS from childhood until menarche onset, recorded by a standardized questionnaire and interview

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Exclusion Criteria

- Women with somatic, psychiatric or neurological diseases or treatments that may impair cognitive functions or are unstable under drug treatment (e.g. thyroid diseases, hypertension, hyperlipidemia) and may influence the parameters to be investigated
- Structural MRI abnormalities that may be associated with cognitive deficits, such as focal lesions (cortical infarction, subdural hematoma, intracerebral hemorrhage or brain tumor) and severe leukoencephalopathies (assessed by Scheltens score)
- Use of psychotropic substances (except medication such as antidepressants, neuroleptics) in the last 3 months
- Antidemential therapy in the last 3 months (e.g. acetylcholine esterase inhibitors, NMDA antagonists)
- current manifest psychiatric disease of axis I disorders according to ICD-10 or DSM-V: addiction disorders (except nicotine), bipolar disorder, schizophrenic disorder, organic mental disorders. Depression, anxiety disorders or post-traumatic stress disorders are not exclusion criteria.
- current cancer
- past immunosuppressive therapy within the last 3 months (e.g. glucocorticoids, cytostatics, antibody therapy, TNF-alpha-blockers, calcineurin inhibitors, TOR inhibitors, interferon therapy)
- MRI contraindications (e.g. pacemakers, metallic or electronic implants, metallic splinters, surgical clamps)
- Medicine or drug abuse
- Claustrophobia
- Pregnancy (recorded via questionnaires on contraindications for MRT examinations)
- Sensorineural hearing loss above 30dB and tinnitus
- Insufficient knowledge of the German language
Additional exclusion criteria control group
- ELS recorded by a standardized questionnaire and an interview


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Addresses

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    • Institut für Medizinische Psychologie der Charité - Universitätsmedizin Berlin
    • Ms.  Prof. Dr. rer. nat.  Christine  Heim 
    • Luisenstraße 57,
    • 10117  Berlin
    • Germany
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    • Berlin Center for Advanced Neuroimaging (BCAN) der Charité
    • 10117  Berlin
    • Germany
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    • Labor Berlin – Charité Vivantes GmbH
    • Sylter Straße 2
    • 13353  Berlin
    • Germany
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    • Klinik für Neurologie mit Experimenteller Neurologie - Universitätsmedizin Berlin, Charité Campus Benjamin Franklin
    • Hindenburgerdamm 30
    • 12203  Berlin
    • Germany
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    • Institut für Biometrie und Klinische Epidemiologie der Charité
    • Reinhardtstraße 58
    • 10117  Berlin
    • Germany
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    • NeuroCure Clinical Research Center (NCRC) der Charité - Universitätsmedizin Berlin
    • Charitéplatz 1
    • 10117  Berlin
    • Germany
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    • Institut für Medizinische Psychologie der Charité - Universitätsmedizin Berlin
    • Ms.  Prof. Dr. rer. nat.  Christine  Heim 
    • Luisenstraße 57,
    • 10117  Berlin
    • Germany
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    • Institut für Medizinische Psychologie der Charité - Universitätsmedizin Berlin
    • Ms.  Maike  Krause 
    • Luisenstraße 57
    • 10117  Berlin
    • Germany
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Sources of Monetary or Material Support

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    • NeuroCure, BrainLab Project Funding
    • Chariteplatz 1
    • 10117  Berlin
    • Germany
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Status

  •   Recruiting ongoing
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Trial Publications, Results and other Documents

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