Clinical trial NCT05528926: RESist Against Irritability Superiority Trial
Official title: Parent Training for the Treatment of Irritability in Children and Adolescents: a Multisite Randomized Controlled, 3-parallel-group, Evaluator-blinded, Superiority Trial
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Irritable Mood
Keywords: Irritability
Parent Management Training (PMT)
Non-Violent Resistance (NVR)
Lead sponsor: University Hospital, Montpellier
Sponsor class: OTHER
First posted: 2022-09-06
Enrollment: 270
Sex: ALL
Minimum age (years): 6
Maximum age (years): 15
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: 3 parallel groups to compare:

* Non-Violent Resistance parent training (NVR)
* Parent Management Training (PMT)
* Treatment As Usual (TAU)
Primary purpose: OTHER

Brief summary: Irritability is defined as developmentally inappropriate proneness to anger. Irritability is a symptom of several mental health conditions in children and adolescents such as attention deficit hyperactivity disorder (ADHD), oppositional defiant disorder (ODD), conduct disorder (CD), depressive disorders, anxiety disorders.Irritability has been associated with poor functional outcomes across the lifespan and was found to be specifically associated with concurrent and longitudinal emotional disorders, suicidality and impaired academic and socio-professional functioning. Children with high irritability also have distinct physiological profiles with hyper-reactivity to stress and perceived threats.

Despite the high prevalence and health issues related to irritability, there is little treatment research on this topic. Developing evidence-based non-pharmacological treatment options for children suffering from severe, chronic irritability is therefore a particularly important target for clinical research.

Detailed description: Irritability is defined as developmentally inappropriate proneness to anger. Irritability is a symptom of several mental health conditions in children and adolescents such as attention deficit hyperactivity disorder (ADHD), oppositional defiant disorder (ODD), conduct disorder (CD), depressive disorders, anxiety disorders. Both tonic (e.g. negative quality of mood) and phasic (e.g. temper outbursts) irritability are criteria of the DSM-5 Disruptive Mood Dysregulation Disorder and the World Health Organization has considered the addition of a specifier to indicate whether ODD presents with chronic irritability and anger in the revision of the International Classification of Disease.

Irritability has been associated with poor functional outcomes across the lifespan and was found to be specifically associated with concurrent and longitudinal emotional disorders, suicidality and impaired academic and socio-professional functioning. Children with high irritability also have distinct physiological profiles with hyper-reactivity to stress and perceived threats.

Irritability is included in the negative valence system of RDoC as "frustrative non-reward". According to this neuroscience-based classification, irritability is an excessive response of an individual faced with the impossibility to achieve an expected goal and has been linked to dysregulations of the autonomic nervous system and the reward network. Another pathophysiological line of research conceptualizes irritability as an aberrant response to threat (e.g. irritable individuals may attack more rapidly and in broader contexts).

Despite the high prevalence and health issues related to irritability, there is little treatment research on this topic. Developing evidence-based non-pharmacological treatment options for children suffering from severe, chronic irritability is therefore a particularly important target for clinical research. One of the first steps in achieving this goal includes testing new therapies against extant interventions. Parent training programs decrease aggressive behaviours in children and are therefore good candidates for the improvement of irritability. Low parental warmth, lack of positive parental emotion socialization and high parental Expressed Emotions have been linked with irritability in children and could therefore be targeted in parental programs.

Research on the biological and psychological mechanisms mediating irritability is also needed to further improve specificity of therapeutic actions.

The project includes two ancyllary studies : RESIST-EXP and RESIST-QUAL.

* RESIST-EXP: Investigate improvement of irritability in both programs throughout emotional testing while collecting ANS functioning measurements.
* RESIST-QUAL: A qualitative interview planned after treatment completion with parents from both parent programme groups.

Eligibility criteria: Inclusion Criteria:

* Male and female subject between 6 and 15 years-old.
* Express informed consent f by at least one of the parents or legal representative, and oral consent of the child.
* A confirmed K-SADS DSM-5 diagnosis of ADHD, ODD, CD, mood/anxiety disorder or DMDD, or a clinical diagnosis of IED. The request of a concomitant mental disorder allows to restrict this intervention to a clinical population.
* A Parental-rated ARI total score of 4 or above at baseline.
* A Clinical Global Impression-Severity score (CGI-S) of 4 or above (=at least moderately ill).
* Persistence of irritability symptoms 6 month or above at baseline (this avoids including children with transitory irritability).
* stable treatment regimen (pharmacological and non-pharmacological) for 2 weeks prior to inclusion and during the trial
* RESIST-QUAL : Same inclusion criteria as above with specific informed consent form signed by the participating parent.

Exclusion Criteria:

* Unavailability of parents or legal representative during the study period.
* Subjects with a DSM-5 diagnosis (clinical presentation or history) that is consistent with Schizophrenia or psychotic disorders or acute manic episodes.
* Diagnosis of Autism Spectrum Disorder (ASD) in patients who are non-verbal and with IQ lower than 70.
* Known or estimated IQ\<70 or clinical diagnosis of intellectual disability.
* Subjects with severe irritability that are better accounted for by another factor, e.g.: general medical condition(s) or direct effect of a substance (i.e., medication, illicit drug use), as determined by the clinical judgment of the investigator, or related to child abuse and/or neglect.
* absence of informed consent give by at least one of the parents or legal representatives, and oral consent of the child
* inability to speak and comprehend French
* deemed unable to comply with the trial protocol
* participation in a structured parent program during the last 6 months

Primary outcomes:
measure: Change from baseline level that measure pleasure and arousal
timeFrame: After 3 months follow-up
Secondary outcomes:
measure: Secondary efficacy endpoint at 1-month follow-up
timeFrame: After 1 month follow-up
measure: Secondary efficacy endpoints at 1 and 3-month follow-up
timeFrame: Between 1 and 3-month follow-up
measure: Secondary efficacy endpoints at 1 and 3-month follow-up
timeFrame: Between 1 and 3-month follow-up
measure: Secondary efficacy endpoints at 1 and 3-month follow-up
timeFrame: Between 1 and 3-month follow-up
measure: Exploratory efficacy endpoints and putative moderators and mediators.
timeFrame: After 3-month follow-up
measure: Exploratory efficacy endpoints and putative moderators and mediators.
timeFrame: At 1 month and 3 months follow-up
measure: Exploratory efficacy endpoints and putative moderators and mediators.
timeFrame: After 3 months follow-up
measure: Exploratory efficacy endpoints and putative moderating and mediating variables.
timeFrame: At 3 months follow-up
measure: Endpoints of the ancillary study: RESIST-EXP
timeFrame: At baseline ans at 3 months follow-up
measure: Endpoints of the ancillary study: RESIST-EXP
timeFrame: At baseline ans at 3 months follow-up
measure: Endpoints of the ancillary study: RESIST-EXP
timeFrame: At baseline ans at 3 months follow-up
measure: Endpoints of the ancillary study: RESIST-EXP
timeFrame: At baseline ans at 3 months follow-up
measure: Endpoints of the ancillary study: RESIST-QUAL
timeFrame: After 3 months follow-up
Other outcomes:
Locations:
city: Montpellier
country: France
facility: UH of Montpellier
Study officials:
References: