Clinical Trial Details
— Status: Not yet recruiting
Administrative data
| NCT number |
NCT05577247 |
| Other study ID # |
APHP220604 |
| Secondary ID |
2022-A01961-42 |
| Status |
Not yet recruiting |
| Phase |
|
| First received |
|
| Last updated |
|
| Start date |
February 15, 2023 |
| Est. completion date |
February 15, 2025 |
Study information
| Verified date |
September 2022 |
| Source |
Assistance Publique - Hôpitaux de Paris |
| Contact |
Philippe FOSSATI, PUPH |
| Phone |
331 42 16 28 91 |
| Email |
philippe.fossati[@]aphp.fr |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Observational
|
Clinical Trial Summary
Major depressive disorder (MDD) is characterized by a cognitive triad of negative beliefs
about oneself, the future and the world. For example, depressed patients hold persistently
negative expectations about the future, despite contradictory evidence, and these strong
negative beliefs are thought to play an important role in the maintenance of depressive
symptoms and potentially in treatment resistance. Indeed, one out of three patients with
major depressive disorder does not respond to conventional, monoaminergic treatments, which
has led to the concept of treatment resistant depression (TRD). It is unknown how the brain
encodes the strong negative beliefs that are insensitive to positive disconfirming
information in TRD patients, and how these neural underpinnings of maladaptive belief
updating are altered by antidepressant treatment.
The principal objective of this study is to gain insight into the brain mechanisms of belief
updating about the future in TRD patients before and after starting ketamine treatment. The
results of this study are expected to provide a better understanding of the neurocognitive
mechanisms of belief-updating in depressed patients, and how these mechanisms contribute to
clinical improvement following ketamine antidepressant treatment.
Description:
Major depressive disorder is characterized by persistently negative expectations about the
future, despite contradictory evidence, and these strong negative beliefs are thought to play
an important role in the maintenance of depressive symptoms and potentially in treatment
resistance. Importantly, some findings indicate that the mechanisms of clinical improvement
involves reductions in negative biases in emotion processing, which is in line with cognitive
theories of depression.
However, it has never been studied if and how antidepressant treatment changes cognitive
biases, which are important for mental health, such as the good news/bad news bias in belief
updating. Moreover, it is also unknown how the brain of TRD patients encodes the strong
negative beliefs that are insensitive to positive disconfirming information.
The study's main goal is to test how the brain encodes belief updating in treatment resistant
depressed patients before compared to early after starting an antidepressant treatment. The
main outcome measure is an interaction between testing time (before vs. after a single
antidepressant dose) and information valence (positive vs. negative belief disconfirming
information) on the brain's oxygenation level dependent signal (BOLD).
The secondary aims involve testing how belief updating changes on the behavioral level and
links to global clinical improvement measured in the clinical care setting. To test these aim
the study will compare the good news/bad new bias in belief updating before and after
ketamine treatment. Tes the correlation of global clinical improvement to the emergence of
the good news/bad news bias following antidepressant treatment.Compare the good news/bad new
bias in belief updating between two groups of patients treated either by ketamine or by
classical monoaminergic antidepressants that are all administered in the patient's natural
clinical care setting.
This study is monocentric. The patients receive antidepressant treatment as part of their
routine medical care and are not randomly assigned to this treatment by the investigator
(contrary to a clinical trial). The study will be run within a natural, measurement-based
care setting.
All patients will be tested two times, before and 24 hours after the first dose of an
antidepressant medication.
A total of 120 patients diagnosed with treatment resistant depression (TRD) will be enrolled
in the proposed study. TRD is defined by non-response to at least two different
antidepressant treatments.
To test the main aim of this study 60 of the 120 TRD patients will be tested with functional
magnetic resonance imaging (fMRI) before or 24h after a single subanaesthetic ketamine
infusion. To be able to test the secondary aims and to run correlational analyses 60 of the
120 patients will be tested solely on the behavioral level before or 24h after a single
monoaminergic antidepressant.
Patients will be randomly assigned to one of two testing time point groups that will involve
testing before or 24h after a first, single antidepressant treatment dosis. Randomization
will be stratified to assure that each testing time group involves an equal number of
participants.
All patients will perform a cognitive belief updating tasks, which comprises 40 trials during
which patients will be presented on a trial-by-trial basis with 40 different adverse lifetime
events and information about their likelihood of occurrence in the general population (base
rates, BR). The adverse lifetime events and their actual base rates are from previously
published work that used to measure belief updating biases in healthy participants and in
depressed patients. In total, 80 adverse lifetime events will be randomly allocated to two
lists of 40 lifetime events and their actual base rates (one list per testing time point).
Following the belief updating task participants will rate a subset of the 40 events on their
positive/negative valence, familiarity, vividness, personal relevance (if already experienced
in the past), controllability and emotional arousal using visual analogous scales (VAS, see
annexe for the events rated). This measure will be used to control all analyses for potential
confounds arising from inter-individual differences on them.
Within the patient's usual care setting the following clinical measures will be obtained for
this study, and are part of the usual psychiatric evaluation:
To assess treatment resistance in unipolar TRD patients, the Maudsley Staging Method will be
administered during the usual patient care setting by an experienced psychiatrist at baseline
prior to the first dose of antidepressant treatment. Global clinical improvement will be
measured with MADRS by the same psychiatrist trained in the administration of the MADRS.
Information about age, gender, level of education will be collected and used as control
variables in all statistical analyses.
