Clinical trial NCT06484803: Resilience Among Trauma Survivors
Official title: Longitudinal Search for Neurobehavioral Underpins of Resilience to Stress
Study type: OBSERVATIONAL
Overall status: ENROLLING_BY_INVITATION
Conditions: PTSD
Keywords: Trauma
Lead sponsor: Tel-Aviv Sourasky Medical Center
Sponsor class: OTHER_GOV
Collaborators: name: Tel Aviv University
First posted: 2024-07-03
Enrollment: 150
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Adult civilians admitted to Tel-Aviv Sourasky Medical Center's Emergency Room (ER), following a potentially traumatic incident.

Brief summary: A major gap remains in understanding the neurobehavioral mechanism of individuals' variability in the dynamic process of responding to traumatic events. To address this gap, the proposed study is focused on two dominant survival processes: acute stress response and motivational behavior. Investigating the involvement of these processes in long-term recovery from a documented traumatic event, our study extends a prior longitudinal investigation in our lab that systematically assessed the neurobehavioral factors contributing to the development of PTSD.

Detailed description: Individual responses to potentially traumatic stress exhibit wide variation, reflecting differences in stress resilience - denoting the capacity to adaptively cope with and recover from adversity (i.e. health despite adversity). To date, growing evidence tracing symptoms' changes following a potentially traumatic event has revealed distinct clinical trajectories, demonstrating variability in the individuals' recovery dynamics following a traumatic event. While some individuals regain homeostasis and recover over time, others experience chronic debilitating dysfunctions and exhibit long-term psychopathology. The current study aims to extend an original longitudinal investigation assessing recent trauma survivors three times within 14 months, with additional clinical and neurobehavioral assessment time points at \~80 months following the exposure to a documented traumatic event. While the previous study focused on assessing neurobehavioral indications of threat and reward sensitivity, this study specifically focused on acute stress response and motivational behavior with respect to trauma recovery trajectory.

Acute stress response involves immediate neurophysiological and psychological reactions to perturbing occurrence, transitioning from a reactive phase to a recovery phase. The reactivity phase is characterized by a threat to physical and mental homeostasis, manifested in multiple neurobiological processes. Subsequently, the stress response transitions to the recovery phase, distinguished by restoring homeostasis and establishing a new memory for coping in the future. The novel dataset collected in this study including fMRI task and resting state, behavioral and biological measurements, enables examination of the neurophysiological mechanism underlying lab-induced acute stress reactivity and recovery and associates it with long-term clinical outcomes following life event adversity. Motivation plays a crucial role in driving the individual's behavior toward a desirable (i.e. rewarding) goal and assists in adaptive coping with the environment. An intriguing finding in the original longitudinal study pointed to the importance of preserved reward processing for resilience. However, the study lacks an exploration of goal-based behavior in motivation which is critical for adaptive coping following stress (e.g. deciding to make an effort and pursue rewarding stimuli despite the possibility of encountering an unpleasant occurrence such as a traumatic reminder). In this project, we posit neurobehavioral aspects of motivational goal-directed behavior (as indicated by approaching or avoiding rewards under risk) will be associated with the long-term dynamics of recovery among trauma survivors. Neuronally, the indicated stress and motivation processes are depicted by functionality patterns in circuits involved in stress and threat (e.g. amygdala, insula, and periaqueductal gray; PAG), motivation (e.g. ventral striatum, orbital-PFC, and Ventral Tegmental Area; VTA) and memory, learning and emotion regulation (e.g. hippocampus and ventromedial-PFC).

In the current study, participants from the initial longitudinal study were recruited for a fourth-time point (\~60 months following trauma exposure) and a fifth-time point (\~80 months following trauma exposure). The fourth evaluation point involved clinical assessment, fMRI scan, physiological measurements, saliva collection for cortisol, and blood sampling (for epigenetic indices). The fifth time point involved home-based self-report questionnaires to evaluate the impact of the October 7th, 2023 events on the participants' clinical status.

Eligibility criteria: Inclusion Criteria:

* Participated in the initial study after an exposure to a traumatic event.
* Age:18 - 70 years.
* Able to read and comprehend Hebrew.

Exclusion Criteria:

* Individuals who can't perform an MRI due to safety reasons (e.g. irremovable metals in their body) or claustrophobia.
* Individuals with a diagnosis of substance abuse, psychotic or bipolar I disorder.
* Individuals with documented head trauma with coma exceeding 30 minutes or with known neurological deficit.

Primary outcomes:
measure: PTSD Clinical trajectories
timeFrame: Approximately 6 years
measure: Change in PTSD symptoms following the October 7th, 2023 events
timeFrame: Half an hour
measure: Change in anxiety symptoms following the October 7th, 2023 events
timeFrame: Half an hour
measure: Change in depressive symptoms following the October 7th, 2023 events
timeFrame: Half an hour
Secondary outcomes:
measure: Neural response to acute stress induction and PTSD resilience
timeFrame: 4 hours
measure: Neural measures of reward and punishment and PTSD resilience
timeFrame: 4 hours
measure: Neurobehavioral Measures of Approach-Avoidance Conflict Related to PTSD Resilience
timeFrame: 4 hours
Other outcomes:
Locations:
city: Tel Aviv
country: Israel
facility: Sourasky Medical Center
Study officials:
References: