Condition category
Not Applicable
Date applied
29/06/2020
Date assigned
15/07/2020
Last edited
07/08/2020
Prospective/Retrospective
Retrospectively registered
Overall trial status
Ongoing
Recruitment status
Recruiting

Plain English Summary

Background and study aims
Stress experienced in the early stages of life – from pregnancy to adolescence – is common and pervasive, affecting up to 75% of pregnant women (and the unborn baby) and nearly 50% of children, with long-term consequences for development and health. The aim of this study is to find out whether early life stress, a well-established risk factor for depressive, cardiovascular (heart) and metabolic disorders individually, is a cause of multiple long-term health conditions (multi-morbidity) in these disorders.

Who can participate?
Children and adults participating in the included population studies:
1. Healthy children at birth
2. Adults aged over 55
3. Adults aged over 18 with depression or anxiety

What does the study involve?
Data from a set of human population studies are used to examine the relationship between early life stress and multi-morbidity across the lifespan, identify potential biological markers and quantify the role of modifiable lifestyle factors (e.g. exercise, diet, sleep, smoking, alcohol use).

What are the possible benefits and risks of participating?
In terms of benefits, this study will increase the health literacy of the participants by making them aware of the negative effects of early life stress on health and disease. This is an observational study with no interventions, so there no risks for the participants.

Where is the study run from?
Rotterdam and Amsterdam (Netherlands), Oulu (Finland) and Bristol (UK)

When is the study starting and how long is it expected to run for?
September 2019 to December 2023

Who is funding the study?
European Commission

Who is the main contact?
1. Karim Lekadir
karim.lekadir@ub.edu
2. Katharina Heil
katharina.f.heil@ub.edu

Trial website

https://earlycause.eu/

Contact information

Type

Scientific

Primary contact

Dr Karim Lekadir

ORCID ID

http://orcid.org/0000-0002-9456-1612

Contact details

Gran Via de les Corts Catalanes 585
Barcelona
08007
Spain
+34 (0)934020852
karim.lekadir@ub.edu

Type

Public

Additional contact

Dr Katharina F Heil

ORCID ID

http://orcid.org/0000-0003-3341-3736

Contact details

Gran Via de les Corts Catalanes 585
Barcelona
08007
Spain
+34 (0)934020852
katharina.f.heil@ub.edu

Additional identifiers

EudraCT number

Nil known

ClinicalTrials.gov number

Nil known

Protocol/serial number

848158

Study information

Scientific title

EarlyCause - causative mechanisms & integrative models linking early life stress to psycho-cardio-metabolic multi-morbidity

Acronym

EarlyCause

Study hypothesis

EarlyCause will investigate the hypothesis that early-life-stress (ELS), as a risk factor for depressive, cardiovascular and metabolic disorders individually, is linked to multi-morbidity between these conditions. From a biological point of view, the main hypothesis is that ELS activates a chain of events leading to cellular, molecular, epigenetic and microbial changes which result in dysregulations of processes across tissues. This causative chain would ultimately trigger specific cellular and tissue phenotypes and comorbid pathological traits in the mental, cardiovascular and metabolic domains.

Ethics approval

Approved 30/11/2019, European Commission (Directorate-General for Research and Innovation, European Commission, Brussels; Tel: not provided; david.canovas-jorda@ec.europa.eu), no ref provided

Study design

Observational study that will leverage existing data from a large set of population research studies (Generation R, ALSPAC, NFBC, Rotterdam, NESDA)

Primary study design

Observational

Secondary study design

Epidemiological study

Trial setting

Other

Trial type

Other

Patient information sheet

Not applicable

Condition

Multi-morbidity between unipolar depression, type 2 diabetes, and coronary heart disease

Intervention

The EarlyCause study will leverage harmonised data from a set of human population studies to examine the relationship between ELS and multi-morbidity across the lifespan, identify potential molecular markers and quantify the protective vs. exacerbating role of modifiable lifestyle factors. These datasets together span from pregnancy to old age, including the well-known Avon Longitudinal Study of Parents and Children (ALSPAC), Generation R Study (GenR), Northern Finland Birth Cohorts (NFBC), ¡Rotterdam Study, and the Netherlands Study of Depression and Anxiety (NESDA). The researchers will make use of correlational multivariate analyses as well as novel latent modelling techniques to model the shared versus unique contribution of ELS on multi-morbid outcomes. The researchers will apply Mendelian randomisation to infer causality using population-based human genetic data., and to establish the molecular mediation of biological markers (DNA methylation, cortisol, inflammation, microbiome) linking ELS exposure to later multi-morbidity. The researchers will also quantify the protective or exacerbating role of modifiable lifestyle factors (e.g. exercise, diet, sleep, smoking, alcohol use) in the relationships of ELS with biological markers and multi-morbidity.

Intervention type

Other

Phase

Drug names

Primary outcome measure

1. Depression assessed using the DSM-IV scale at each round of data collection (every 2-5 years depending on the dataset)
2. Diabetes type 2 assessed using the glycated hemoglobin test at each round of data collection (every 2-5 years depending on the dataset)
3. Coronary heart disease assessed using standard cardiovascular exams (biomarkers, imaging, ECG) at each round of data collection (every 2-5 years depending on the dataset)

Secondary outcome measures

EarlyCause will re-use the outcomes already measured by the Generation R, ALSPAC, NFBC, Rotterdam and NESDA studies at each round of data collection (every 2-5 years depending on the study):
1. Depressive symptoms assessed using the Centre for Epidemiological Studies Depression Scale (CESD) at each round of data collection (every 2-5 years depending on the dataset)
2. Glucose level assessed using glycated hemoglobin test at each round of data collection (every 2-5 years depending on the dataset)
3. Hypertension assessed using blood pressure test (mmHg) at each round of data collection (every 2-5 years depending on the dataset)

Overall trial start date

04/09/2019

Overall trial end date

31/12/2023

Reason abandoned (if study stopped)

Eligibility

Participant inclusion criteria

The inclusion criteria are the same as those of the population studies included in EarlyCause:
1. Generation R, ALSPAC, NFBC: Healthy children at birth
2. Rotterdam: Adults > 55
3. NESDA: Adults > 18 with DSM-IV diagnosis of depression (minor or major depression, dysthymia) or anxiety

Participant type

Mixed

Age group

Mixed

Gender

Both

Target number of participants

70,000

Participant exclusion criteria

For NESDA, severe mental health (e.g. psychosis, bipolar disorder, obsessive-compulsive disorder, or severe addiction) or disability

Recruitment start date

01/01/2020

Recruitment end date

31/12/2023

Locations

Countries of recruitment

Finland, Netherlands, United Kingdom

Trial participating centre

Erasmus Medical Centre Rotterdam
Doctor Molewaterplein 40
Rotterdam
3015 GD
Netherlands

Trial participating centre

University of Oulu
Pentti Kaiteran katu 1
Oulu
90570
Finland

Trial participating centre

VU University Medical Center Amsterdam
De Boelelaan 1117
Amsterdam
1081 HV
Netherlands

Trial participating centre

University of Bath
Claverton Down
Bath
BA2 7AY
United Kingdom

Sponsor information

Organisation

European Commission

Sponsor details

Directorate-General for Research and Innovation
Brussels
1049
Belgium
+32 (0)2 299 11 11
David.CANOVAS-JORDA@ec.europa.eu

Sponsor type

Government

Website

http://ec.europa.eu/index_en.htm

Funders

Funder type

Government

Funder name

Horizon 2020 Framework Programme

Alternative name(s)

EU Framework Programme for Research and Innovation H2020, Horizon 2020, Programa Marco Horizonte 2020, Program ramowy Horyzont 2020, Programme-cadre Horizon 2020, Programma quadro Orizzonte 2020, Rahmenprogramm Horizont 2020, H2020

Funding Body Type

government organisation

Funding Body Subtype

National government

Location

Results and Publications

Publication and dissemination plan

Peer-reviewed international journals such as:
1. Journal of Developmental Origins of Health and Disease
2. International Journal of Epidemiology

IPD sharing statement
The datasets generated during and/or analysed during the current study are not expected to be made available due to legal issues, consents and data policies of the included population studies.

Intention to publish date

31/12/2023

Participant level data

Not expected to be available

Basic results (scientific)

Publication list

Publication citations

Additional files

Editorial Notes

07/08/2020: Uploaded protocol (not peer reviewed) Version n/a (2 files). 30/06/2020: Trial's existence confirmed by the European Commission.