Predictive Elements of Trauma and Its After-effects: Importance of the Quality of Neurobiological Response to Stress (LIFT-UP)

The neurobiological response to stress is an adaptive response allowing us to cope with the multiple aggressions of daily life. This response orchestrates the body's systemic reaction. The intensity of response to stress can modify the body's functioning, which implies a variety of fields where biomarkers may be isolated: immunity, psychology, neurophysiology, integrative physiology. When stress is too intense or prolonged, response to stress may become misfitted and deleterious.

This study is based on the hypothesis that a severe physical or psychological trauma is associated with an intense and misfitted stress that is responsible from an undue immuno-inflammatory activation (through sympathetic activation). The result is a subinvasive state of systemic and tissue inflammation (low-noise inflammation), responsible for the mid-term deleterious consequences of the traumatic event.

The objective of this study is to understand how the dysregulation of intense stress simultaneously generates an initial pathological state and an alteration of mid-term evolution (which is considered as a poor prognosis and/or as responsible for after-effects).

The investigators wish to identify relevant biomarkers of the mechanisms activated during intense stress and influencing the immuno-inflammatory and epigenetic spheres with deleterious consequences on physiological and psychological functions.

Study Overview

• Status: Recruiting
• Conditions: Stress Reaction
• Intervention / Treatment: Other: Blood collection; Other: Saliva collection; Other: Electrocardiography (ECG); Behavioral: Questionnaires

• Study Type: Observational
• Enrollment (Anticipated): 130

Contacts and Locations

• Study Contact: Name: Anaïs DUFFAUD; Phone Number: +33 178651315; Email: anais.duffaud@intradef.gouv.fr

Study Locations

• France
  • Bordeaux, France, 33000
    • Not yet recruiting
    • CHU Pellegrin
    • Contact: Cédric GIL-JARDINE, MD
  • Clamart, France, 92140
    • Not yet recruiting
    • Hôpital d'Instruction des Armées PERCY
    • Contact: Sylvain MARTINEZ, MD
  • Saint-Mandé, France, 94163
    • Not yet recruiting
    • Hopital d'Instruction des Armees BEGIN
    • Contact: Diane COMMANDEUR, MD
  • Toulon, France, 83800
    • Recruiting
    • Hôpital d'Instruction des Armées Sainte-Anne
    • Contact: Julien BORDES, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 70 years and older (Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Patients admitted to the emergency room for a fracture of the upper end of the femur.

Description

Inclusion Criteria:

• Fracture of the upper end of the femur
• Cognitive state allowing the understanding of questionnaires

Exclusion Criteria:

• Traumatic Brain Injury
• Chronic inflammatory or immune pathologies
• On anticoagulants
• On neuroleptic or antidepressant treatment
• Pathology or health condition not allowing 1-year survival

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Occurrence of depression	Screening for depression will be done using a validated self-report questionnaire, the Geriatric Depression Scale Short Version (GDS). We will use the threshold value of 10 (score > or =) which corresponds to a very high probability of depression.	12 months following surgery
Occurrence of "psychosomatic death"	The diagnosis of "psychosomatic death" will be made by a physician. There is no consensus on the diagnosis of this syndrome. However, a patient with "psychosomatic death" is likely to be hospitalized or followed up medically and will not be able to respond to the investigator's request for a telephone interview.	12 months following surgery
Occurrence of death	Vital status will be collected from the participant's family or referring physician or at the birth & death record service (of the participant's town)	12 months following surgery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Evolution of heart rate variability between enrollment and Visit 1	Heart rate variability will be assessed using electrocardiography recordings	Between enrollment and Visit 1 (45-60 days following surgery)
Evolution of perceived stress level between enrollment and Visit 1	Perceived stress level will be assessed with the Perceived Stress Scale (PSS). Individual scores on the PSS can range from 0 to 40 with higher scores indicating higher perceived stress.	Between enrollment and Visit 1 (45-60 days following surgery)
Evolution of anxiety level between enrollment and Visit 1	Anxiety level will be assessed with the French version of Spielberger's State-Trait Anxiety Inventory adapted for people aged 65 and older (IASTA-Y65+). Individual scores on the IASTA-Y 65+ can range from 20 to 80 with higher scores indicating higher anxiety.	Between enrollment and Visit 1 (45-60 days following surgery)
Evolution of post-traumatic stress disorder severity level between enrollment and Visit 1	Post-traumatic stress disorder severity will be assessed with the Post-traumatic stress disorder CheckList for DSM-5 (Diagnostic and Statistical Manual Diploma in Social Medicine) (PCL-5) scale. Individual scores on the PCL-5 can range from 0 to 80 with higher scores indicating higher post-traumatic stress disorder severity.	Between enrollment and Visit 1 (45-60 days following surgery)
Evolution of quality of life between enrollment and Visit 1	Quality of life will be assessed using the abbreviated version of the World Health Organization Quality of Life (WHOQOL-Bref). The WHOQOL-Bref is grouped into 4 domains : Physical health (score range from 7 to 35); Psychological health (score range from 6 to 30); Social relationships (score range from 3 to 15); Environment (score range from 8-40) Higher scores indicate higher quality of life.	Between enrollment and Visit 1 (45-60 days following surgery)
Evolution of cortisol level between enrollment and Visit 1	Cortisol level will be measured in saliva sample.	Between enrollment and Visit 1 (45-60 days following surgery)
Evolution of GABA level between enrollment and Visit 1	Gamma-aminobutyric acid (GABA) level will be measured in blood sample.	Between enrollment and Visit 1 (45-60 days following surgery)
Evolution of oxydative stress level between enrollment and Visit 1	Oxydative stress level will be measured in blood sample.	Between enrollment and Visit 1 (45-60 days following surgery)
Evolution of BDNF level between enrollment and Visit 1	Brain-derived neurotrophic factor (BDNF) level will be measured in blood sample.	Between enrollment and Visit 1 (45-60 days following surgery)
Evolution of pro and anti-inflammatory cytokines level between enrollment and Visit 1	Cytokines level will be measured in blood sample.	Between enrollment and Visit 1 (45-60 days following surgery)
Evolution of IGF-1 level between enrollment and Visit 1	Insulin like growth factor type 1 (IGF-1) will be measured in blood sample.	Between enrollment and Visit 1 (45-60 days following surgery)
Evolution of NPY level between enrollment and Visit 1	Neuropeptide Y (NPY) level will be measured in blood sample.	Between enrollment and Visit 1 (45-60 days following surgery)
Evolution of NPS between enrollment and Visit 1	Neutrophil-platelet score (NPS) will be measured in blood sample.	Between enrollment and Visit 1 (45-60 days following surgery)
Evolution of ocytocin level between enrollment and Visit 1	Ocytocin level will be measured in blood sample.	Between enrollment and Visit 1 (45-60 days following surgery)
Evolution of methylation of genes coding for BDNF between enrollment and Visit 1	Methylation of genes coding for BDNF will be measured on DNA extracted from blood sample.	Between enrollment and Visit 1 (45-60 days following surgery)
Evolution of methylation of genes coding for glucocorticoid receptors between enrollment and Visit 1	Methylation of genes coding for glucocorticoid receptors will be measured on DNA extracted from blood sample.	Between enrollment and Visit 1 (45-60 days following surgery)

Collaborators and Investigators

• Sponsor: Direction Centrale du Service de Santé des Armées

Study record dates

Study Major Dates

• Study Start (Actual): November 4, 2020
• Primary Completion (Anticipated): May 1, 2023
• Study Completion (Anticipated): May 1, 2023

Study Registration Dates

• First Submitted: August 25, 2020
• First Submitted That Met QC Criteria: August 27, 2020
• First Posted (Actual): August 28, 2020

Study Record Updates

• Last Update Posted (Actual): April 28, 2023
• Last Update Submitted That Met QC Criteria: April 27, 2023
• Last Verified: April 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Fractures, Bone; Wounds and Injuries; Fractures, Stress
• Other Study ID Numbers: 2018PPRC30; 2019-A01811-56 (Other Identifier: IDRCB)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No