Clinical trial NCT03821779: Prefrontal Oscillations in Social Anxiety Disorder (POSAD)
Official title: Study of Slow Prefrontal Cortex Oscillations During Social Exposure in Social Anxiety Disorder
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Anxiety Disorders
Anxiety
Anxiety and Fear
Lead sponsor: Institut National de la Santé Et de la Recherche Médicale, France
Sponsor class: OTHER_GOV
First posted: 2019-01-30
Enrollment: 30
Sex: ALL
Minimum age (years): 20
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Intervention model description: First phase (go-no-go) with 10 subjects in 1 arm Second phase with 20 subjets (2 arms) in a cross-over design.
Primary purpose: BASIC_SCIENCE

Brief summary: Experimental fear in rodents is correlated with slow oscillations in electrical recordings of prefrontal cortex activities. The present study aims to test whether slow prefrontal oscillations is a biomarker of pathological anxiety in human subjects.

Detailed description: Fear and anxiety are adaptive responses that may become excessive or inappropriate in pathological conditions, as defined as anxiety disorders in DSM-5. These disorders, including phobic disorders such as social anxiety disorder, are frequent and impairing in the general population, with an estimated lifetime prevalence of 28% and significant consequences on quality of life. Direct and indirect medical costs related to these conditions amount to 74.4 billion €/year in Europe. Despite their prevalence, debilitating nature and chronicity, the pathophysiology of anxiety disorders is poorly understood and neurobiological treatments, including pharmacotherapy, are lacking efficacy. A better understanding of the neuronal mechanisms implicated in anxiety is necessary for the conception of new approaches to treat pathological anxiety.

Anxiety is commonly modeled in animals using fear conditioning, which consists in associating a neutral stimulus (eg: a sound) with a mild electrical foot-shock. As a result of the association between sound and shock, sound presentation in isolation induces a set of conditioned behavioral responses, such as an immobilization ("freezing"). Previous studies have shown that the expression of fear responses, measured on the basis of freezing, is associated with the emergence of slow oscillations (2-6Hz) in medial prefrontal cortex (mPFC) of mice. Moreover, emergence of these oscillations in mPFC is predictive of the occurrence of freezing, and the artificial induction of 4 Hz oscillations in mPFC with optogenetics induces freezing. Finally, inhibiting neurons in mPFC during the ascending phase of this slow mPFC oscillation at the time of conditioned sound presentation is sufficient to significantly reduce fear.

Interestingly, these results obtained in mice seem to find their prolongation in humans. Recent studies using fear conditioning in human subjects have also reported the emergence of prefrontal slow oscillations between 2-6 Hz during expression of conditioned fear responses. These results suggests that common mechanisms underlie the expression of fear in humans and rodents. However, whether similar neuronal circuits and mechanisms are implicated in human anxiety disorders remains unknown.

This study aims at assessing the presence of slow mPFC oscillations during expression of anxiety in patients suffering from anxiety disorders. Beyond understanding of the neuronal mechanisms underlying anxiety expression, this study could provide a biomarker of anxiety with diagnostic and therapeutic implications.

Eligibility criteria: Inclusion Criteria:

* Social anxiety disorder as defined in DSM-5
* Full understanding of the protocol
* Obtaining informed consent from study subjects before or at inclusion at the latest
* Being registered in the french national health insurance service (Sécurité Sociale) (or equivalent)

Exclusion Criteria:

* Active medical co-morbidity including severe hypertension, cardiac insufficiency, Raynaud syndrome, diabetes mellitus, renal insufficiency, adrenal insufficiency, Cushing syndrome and epilepsy
* Severe neurological co-morbidity, including but not limited to Parkinson's disease and multiple sclerosis
* Long-term corticotherapy
* History of significant head injury, defined by loss of consciousness
* Being diagnosed with another major psychiatric condition (DSM5) including bipolar disorder and schizophrenia or substance/alcohol use disorder; with the exception of major depressive disorder and nicotine use disorder
* Suicidal risk evaluated as moderate to high in the MINI questionnaire
* initiation of a psychotropic treatment or change in the dose of ongoing psychotropic treatment within 3 days prior to each visit and including:

  1. antidepressant treatments with selective serotonin recapture inhibitors, serotonin and norepinephrine inhibitors, alpha2-presynaptic adrenoreceptors (mirtazapine, mianserin), tricyclic
  2. anxiolytic drugs including benzodiazepines and anti-histamine
  3. antipsychotic drugs
* Acute alcohol intake 2 days prior to each visit (inclusion, experimental sessions)
* Pregnancy or breastfeeding.
* Ongoing hospitalization without consent (decision of a third-party: medical, justice)

Primary outcomes:
measure: Change in power of slow oscillations in prefrontal EEG recordings during anticipation relative to baseline
timeFrame: During the 5 minutes before oral presentation and during the 1 hour rest period
Secondary outcomes:
measure: Duration of prefrontal slow oscillations epochs during anticipation
timeFrame: During the 5 minutes before oral presentation
Other outcomes:
measure: Change in power of slow oscillations in prefrontal EEG recordings during presentation relative to baseline
timeFrame: During the 5 minutes oral presentation and during the 1 hour rest period.
measure: Duration of prefrontal slow oscillations epochs during presentation
timeFrame: During the 5 minutes oral presentation
measure: Correlation between prefrontal slow oscillations power during anticipation and anxiety score
timeFrame: During the 5 minutes before oral presentation
measure: Correlation between prefrontal slow oscillations power during presentation and anxiety score
timeFrame: During the 5 minutes oral presentation
measure: Correlation between prefrontal slow oscillations duration during anticipation and anxiety score
timeFrame: During the 5 minutes before oral presentation
measure: Correlation between prefrontal slow oscillations duration during presentation and anxiety score
timeFrame: During the 5 minutes oral presentation
measure: Correlation between prefrontal slow oscillations power during anticipation and trait anxiety
timeFrame: During the 5 minutes before oral presentations (PFC oscillations power) and prior to inclusion (STAI-B rating)
measure: Correlation between prefrontal slow oscillations power during presentation and trait anxiety
timeFrame: During the 5 minutes oral presentation (PFC oscillations power) and prior to inclusion (STAI-B rating)
measure: Correlation between prefrontal slow oscillations duration during anticipation and trait anxiety
timeFrame: During the 5 minutes before oral presentation (PFC oscillations duration) and prior to inclusion (STAI-B rating)
measure: Correlation between prefrontal slow oscillations duration during presentation and trait anxiety
timeFrame: During the 5 minutes oral presentation (PFC oscillations duration) and prior to inclusion (STAI-B rating)
measure: Correlation between prefrontal slow oscillations power during anticipation and state anxiety
timeFrame: During the 5 minutes before oral presentation (PFC oscillations power) and prior to inclusion (STAI-A rating)
measure: Correlation between prefrontal slow oscillations power during presentation and state anxiety
timeFrame: During the 5 minutes oral presentation (PFC oscillations power) and prior to inclusion (STAI-A rating)
measure: Correlation between prefrontal slow oscillations duration during anticipation and state anxiety
timeFrame: During the 5 minutes before oral presentation (PFC oscillations duration) and prior to inclusion (STAI-A rating)
measure: Correlation between prefrontal slow oscillations duration during presentation and state anxiety
timeFrame: During the 5 minutes oral presentation (PFC oscillations duration) and prior to inclusion (STAI-A rating)
measure: Correlation between prefrontal slow oscillations power during anticipation and levels of social anxiety
timeFrame: During the 5 minutes before oral presentation (PFC oscillations power) and prior to inclusion (LSAS rating)
measure: Correlation between prefrontal slow oscillations power during presentation and levels of social anxiety
timeFrame: During the 5 minutes oral presentation (PFC oscillations power) and prior to inclusion (LSAS rating)
measure: Correlation between prefrontal slow oscillations duration during anticipation and levels of social anxiety
timeFrame: During the 5 minutes before oral presentation (PFC oscillations duration) and prior to inclusion (LSAS rating)
measure: Correlation between prefrontal slow oscillations duration during presentation and levels of social anxiety
timeFrame: During the 5 minutes oral presentation (PFC oscillations duration) and prior to inclusion (LSAS rating)
measure: Correlation between prefrontal slow oscillations power during anticipation and levels of general anxiety
timeFrame: During the 5 minutes before oral presentation (PFC oscillations power) and prior to inclusion (BAS rating)
measure: Correlation between prefrontal slow oscillations power during presentation and levels of general anxiety
timeFrame: During the 5 minutes oral presentation (PFC oscillations power) and prior to inclusion (BAS rating)
measure: Correlation between prefrontal slow oscillations duration during anticipation and levels of general anxiety
timeFrame: During the 5 minutes before oral presentation (PFC oscillations duration) and prior to inclusion (BAS rating)
measure: Correlation between prefrontal slow oscillations duration during presentation and levels of general anxiety
timeFrame: During the 5 minutes oral presentation (PFC oscillations duration) and prior to inclusion (BAS rating)
measure: Correlation between prefrontal slow oscillations power during anticipation and depression levels
timeFrame: During the 5 minutes before oral presentation (PFC oscillations power) and prior to inclusion (MARDS rating)
measure: Correlation between prefrontal slow oscillations power during presentation and depression levels
timeFrame: During the 5 minutes oral presentation (PFC oscillations power) and prior to inclusion (MARDS rating)
measure: Correlation between prefrontal slow oscillations duration during anticipation and depression levels
timeFrame: During the 5 minutes before oral presentation (PFC oscillations duration) and prior to inclusion (MARDS rating)
measure: Correlation between prefrontal slow oscillations duration during presentation and depression levels
timeFrame: During the 5 minutes oral presentations (PFC oscillations duration) and prior to inclusion (MARDS rating)
Locations:
city: Bordeaux
country: France
facility: GENPHASS, SANPSY, CHU de Bordeaux
Study officials:
affiliation: Centre Hospitalier Charles Perrens, Bordeaux; INRA NutriNeuro, Bordeaux; Université de Bordeaux, France
name: Olivier Doumy, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Centre Hospitalier Charles Perrens, Bordeaux; Université de Bordeaux, France
name: Alexandra Bouvard, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Neurocentre Magendie, Inserm U1215, Bordeaux, France
name: Cyril Herry, PhD
role: STUDY_DIRECTOR
affiliation: Neurocentre Magendie, Inserm U1215, Bordeaux, France
name: Cyril Dejean, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Centre Hospitalier Charles Perrens, Bordeaux; Neurocentre Magendie, Inserm U1215, Bordeaux, France
name: Thomas Bienvenu, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: GENPHASS, CHU de Bordeaux
name: Jacques Taillard, MS
role: PRINCIPAL_INVESTIGATOR
affiliation: Centre Hospitalier Charles Perrens, Bordeaux; INRA NutriNeuro, Bordeaux; Université de Bordeaux, France
name: Bruno Aouizerate, MD-PhD
role: STUDY_CHAIR
References: