Clinical Trial Details
— Status: Active, not recruiting
Administrative data
| NCT number |
NCT05293431 |
| Other study ID # |
2021365 |
| Secondary ID |
|
| Status |
Active, not recruiting |
| Phase |
N/A
|
| First received |
|
| Last updated |
|
| Start date |
September 1, 2022 |
| Est. completion date |
November 15, 2023 |
Study information
| Verified date |
June 2023 |
| Source |
Institut Guttmann |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
Background:
By the end of 2020, the coronavirus disease (COVID-19) pandemic resulted in over 84 million
cases and nearly 2 million deaths.
Continued confinement and restriction are expected to negatively affect mental health,
however, some individuals are likely to show much less negative impact than others. The
characterization and neurobiological determinants of brain resilience vs vulnerability during
the pandemic should generate critical knowledge and open future avenues for individually
tailored interventions.
Objectives:
1. Identify the individual psychobiological determinants of resilience during COVID-19
pandemic.
2. Conduct a non-invasive brain stimulation intervention to modulate the expression of
resilience brain networks.
Methods:
Barcelona Brain Health Initiative participants will be included, encompassing multiple
assessments before and during the COVID-19 pandemic. Machine learning techniques will be
applied to define brain networks signature of resilience. Subsequently transcranial
alternating stimulation will be used during a controlled trial intervention to promote the
expression of brain resilience networks.
Expected results:
The present project should provide critical new knowledge on brain mechanisms underlying
resilience and first evidences of the feasibility and impact of modulating brain resilience
networks in terms of its effects on mental health of participants.
Description:
As of the end of 2020, the coronavirus (COVID-19) pandemic had resulted in over 88 million
confirmed cases and nearly 2 million deaths worldwide. Recurring waves of infection are
forcing to impose continuing social restrictions and confinement measures all around the
world.
From a public health perspective, these measures could potentially have an important negative
impact on society and has led to the call for development of preventive and interventional
strategies.
However despite the generalized negative effects of infection some individuals seem
relatively protected from negative sequelae. Therefore, some people appear to be particularly
resilient and the characterization and better understanding of characteristics that explain
why some remain resilient has been highlighted as a critical focus of needed research, as it
allows the potential to identify factors that can be targets for designing interventional
strategies.
Resilience, the concept that describes the capacity of certain individuals to resist the
impact of illness and distress, is a broad term. In clinical psychology and mental health,
the concept of resilience has been historically been linked to the study of individual
differences (e.g., self-esteem, sense of control, perception of social support, etc.) that
determine the capacity to cope with the impact of life traumas in order to maintain normal
psychological and physical functioning and avoid serious mental illness.
Beyond the psychological aspects, the determinants and factors that confer individual
differences in resilience require integrated assessment of specific person's social context,
engagement in positive lifestyles, and their interplay with its brain biological substrates
and mechanisms. Neuroimaging investigations have identified brain regions that show specific
activity and connectivity patterns during exposure to stressful or violent stimuli and that
may be correlated with scores in psychosocial scales of resilience or predict subsequent
coping abilities. Within the field of ageing and dementia some studies have suggested the
role of the frontal cortex, specifically the functional connectivity of the dorsolateral
prefrontal cortex to the rest of the brain or to particular networks (DMN, SN), as a neural
substrate of higher resilience, both in normal aging.
A critical aspect to consider is that, while it is tempting to leverage such neuroimaging
studies to try to identify a "human brain network of resilience", animal work on the neural
substrate of resilience illustrates the importance of interventional experimental designs
that employ stimuli that can be precisely quantified and controlled. Novel neuroscience
approaches allow to undertake substantial translational work to enable the study of the
neural substrates of resilience in humans, probing in a more direct causal association
between brain circuit function and metrics of cognitive function or behavioral assessment -
or subjective, i.e., related to wellbeing. As an example, the stress-response paradigm,
offers a useful framework for the definition and study of resilience. It consists of three
principal elements 1) a stressor; 2) an organism response; and 3) a given outcome.
Importantly, the experimental approach can also be applied to directly modulate the activity
of brain networks subtending resilience processes.
Methods:
Can be actively modulate resilience? The main objective of subproject is to test the
possibility to modulate the activity of the neural network underlying resilience and
investigate the effects at the level of observable behavioral and neurophysiological changes.
Researchers propose a double-blind brain stimulation study.
Participants Participants will be pseudo-randomly selected, stratifying where possible for
socio-demographical variables, amongst those individuals previously defined as "vulnerable".
Sample size was calculated considering the effect size of the few previous studies
investigating the modulatory effect of non-invasive brain stimulation on functional and
behavioral outcomes of resilience to stress previous studies of our group that showed how
different non-invasive brain stimulation technique could differently modulate functional
magnetic resonance (fMRI) derived brain networks dynamics or studies that employed stressor
paradigms tasks to explore brain networks organization.
Non-invasive brain stimulation researchers will use transcranial alternating current
stimulation (tACS), combined with neuroimaging data and high density EEG (hdEEG).
tACS utilizes low-amplitude alternating currents to modulate brain activity and entrain
specific brain oscillations depending on the applied stimulation frequency. Researchers
previously developed a method for optimizing the configuration of multifocal tACS for
stimulation of specific brain networks (which effect can outlast the duration of stimulation
and the use of a novel (sham) control stimulation paradigm will ensure the proper blinding of
all participants.
tACS study protocol: general montage and configuration procedures tACS montages will be
designed with the Stimweaver montage optimization algorithm to determine the positions and
currents of the electrodes over the scalp that induce an electric field in the brain that
better approximates a weighted target electric field map. Stimulation will be delivered using
8 circular electrodes with an area of 8 cm2. For safety issues, the maximum current delivered
by any electrode will be 2 milliampere (mA), while the maximum current injected through all
the electrodes will be 4 mA. In the real intervention conditions, the current will be
supplied during the whole experimental session. In all groups, the current will be initially
increased and finally decreased in a 30 s ramp-up and ramp-down fashion. For the sham
condition, the current dosage will be composed of an initial ramp-up of 30 s immediately
followed by a 1 min ramp- down, and a final ramp-down of 30 s immediately preceded by a
ramp-up of 1 min. All stimulation parameters will adhere to general transcranial electrical
stimulation current safety criteria guidelines.
Pre-post experimental stress coping paradigm To induce stress, researchers will use the
moving-circles paradigm. In this task there are two circles moving sometimes closer and at
times moving away from each other. When the circles touch, participants are delivered a mild
electric stressor. Circle movement has a high degree of unpredictability and the circles
might approach each other such that the stressor is more imminent, and then retreat from each
other for a period.
Study design:
Double-blind controlled tACS study In order to evaluate the effect of stimulation on the
modulation of the resilience networks, the researchers will implement a double-blind
controlled trial using tACS.
Participants will receive tACS stimulation in two conditions which will be administered in a
counterbalanced manner. In the first condition the researchers will target nodes of the
resilience network identified by subproject#1, and in the second condition participants will
receive sham stimulation. The study will be conducted in a double-blind manner.
