Clinical trial NCT04985344: Treatment of Pediatric Post-traumatic Stress Disorder With Memory Reactivation Under the Influence of Propranolol
Official title: Treatment of Pediatric Post-traumatic Stress Disorder With Memory Reactivation Under the Influence of Propranolol: A Randomized Placebo-controlled Trial. PPP
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: PTSD
Keywords: PTSD
traumatic memory reactivation
pediatric
Propranolol
Post-traumatic stress disorder
Lead sponsor: University Hospital, Toulouse
Sponsor class: OTHER
First posted: 2021-08-02
Enrollment: 92
Sex: ALL
Minimum age (years): 7
Maximum age (years): 12
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: By age 18, roughly 8% of traumatized youth have met criteria for a diagnosis of PTSD, with numbers rising up to 40% in cases of sexual abuse and assault. To date there is no empirical support for the use of psychopharmacological interventions as treatment of pediatric PTSD. Trauma-focused psychotherapeutic/TFP approaches should be favored in childhood PTSD. However, when compared to active control conditions, TFP produced a mean effect size on child and adolescents population (g=0.83). Moreover, in therapies with a substantial exposure component, the intense and lengthy reexperiencing of the traumatic event results in a substantial proportion of participants dropping out.

The reactivation of a previously consolidated memory can make it labile, subsequently requiring a re-stabilization of it called reconsolidation of the memory.

Acting on these reconsolidation processes makes possible to interfere with the subsequent storage of this memory.

Detailed description: By age 18, roughly 8% of traumatized youth have met criteria for a diagnosis of PTSD, with numbers rising up to 40% in cases of sexual abuse and assault. To date there is no empirical support for the use of psychopharmacological interventions as treatment of pediatric PTSD. Trauma-focused psychotherapeutic/TFP approaches should be favored in childhood PTSD. However, when compared to active control conditions, TFP produced a mean effect size on child and adolescents population (g=0.83). Moreover, in therapies with a substantial exposure component, the intense and lengthy reexperiencing of the traumatic event results in a substantial proportion of participants dropping out.

The reactivation of a previously consolidated memory can make it labile, subsequently requiring a re-stabilization of it called reconsolidation of the memory.

Acting on these reconsolidation processes makes possible to interfere with the subsequent storage of this memory.

The combination of the targeted reactivation of the traumatic memory and the intake of an agent that decreases the reconsolidation can thus disrupt the recall of unwanted memories and thus serve as a treatment for people suffering from traumatic memories, such as in PTSD.

Since stimulation of β-noradrenergic receptors facilitates the consolidation of memories as well as their re-consolidation, an antagonist of these receptors, propranolol, has generated considerable interest as a treatment to alleviate emotional and traumatic memories in individuals with PTSD.

In adults diagnosed with long-standing PTSD two 6-week, double-blind, placebocontrolled, randomised clinical trials, one in 60 subjects and the other in 67 have shown promising results. PTSD participants who actively recalled their traumatic event under the influence of propranolol once a week for up to 6 weeks showed a substantial decrease in symptom ratings compared with placebo. Thus, all of this data led the team to propose a comparable design study in children with PTSD

Eligibility criteria: Inclusion Criteria:

* Children aged 7-12 years
* CPTS-RI total score ≥40
* Primary diagnosis of PTSD (6 months or more after the traumatic event)
* Heart rate ≥ 55 bpm
* Systolic blood pressure ≥ 95 mm Hg
* Affiliation to a social security scheme
* Written consent signed by the parents/holders of parental authority and the investigator
* Acceptance of the protocol by the child-Child and Parents/Holders of parental authority fluent in French

Exclusion Criteria:

* Age\<7 years or ≥13 years
* Children whose parents have been deprived of their authority
* Contraindication to propranolol (cardiogenic shock, sinus bradycardia, hypotension (\< fifth percentile oscillometric or \<2SD) (Banker et al., 2016 - see APPENDIX 1), greater than first-degree heart block, heart failure, bronchial asthma and hypersensitivity to propranolol hydrochloride)
* Concurrent medication with possible interactions with propranolol (cf 8.2)
* Concurrent psychotropic drugs that have been shown to be effective in improving symptoms of PTSD (Antidepressants, atypical antipsychotics, mood stabilizers)
* Concurrent psychotherapy (\>1 structured session/month declared by the clinician who follows the child)
* Current active psychosis, anorexia nervosa, bulimia nervosa, binge-eating disorder, attention-deficit hyperactivity disorder, autism spectrum disorder
* Children with psoriasis
* Children with a predisposition to hypoglycemia
* Obsessive-compulsive disorders
* Bipolar Disorders
* Mental retardation,
* Traumatic brain injury (loss of consciousness \> 10 minutes)
* Currently treated with a bradycardic drug
* Concurrent participation to another interventional study
* Renal or Hepatic Impairment
* Pregnancy

Primary outcomes:
measure: Child Post-Traumatic Stress Reaction Index/CPTS-RI
timeFrame: week 8
Secondary outcomes:
measure: Child Post-Traumatic Stress Reaction - Week 32 Index/CPTS-RI
timeFrame: week 32
measure: Child Post-Traumatic Stress Reaction - Week 60 Index/CPTS-RI
timeFrame: week 60
measure: Child PTSD Checklist-Child version/CPC-C total score
timeFrame: Week 8
measure: Child PTSD Checklist-Child version/CPC-C total score - Week 32
timeFrame: Week 32
measure: Child PTSD Checklist-Child version/CPC-C total score - Week 60
timeFrame: Week 60
measure: Child PTSD Checklist-Parent version/CPC-P total score - Week 32
timeFrame: Week 32
measure: Child PTSD Checklist-Parent version/CPC-P total score - Week 60
timeFrame: Week 60
measure: Child PTSD Checklist-Parent version/CPC-P total score
timeFrame: Week 8
measure: Kiddie-SADS-Present and Lifetime Version DSM-5/K-SADS-PL-DSM5
timeFrame: week 8
measure: Current diagnosis of PTSD at Week 32
timeFrame: week 32
measure: Children Depression Inventory/CDI total score
timeFrame: week 8
measure: Children Depression Inventory/CDI total score - Week 32
timeFrame: week 32
measure: Children Depression Inventory/CDI total score - Week 60
timeFrame: week 60
measure: Children's Sleep Habits Questionnaire/CSHQ Parent version total score
timeFrame: week 8
measure: Children's Sleep Habits Questionnaire/CSHQ Parent version total score - Week 32
timeFrame: week 32
measure: Children's Sleep Habits Questionnaire/CSHQ Parent version total score - Week 60
timeFrame: week 60
measure: Comorbidity of other mental disorders
timeFrame: week 8
measure: Corsi Blocks task
timeFrame: week 8
measure: CGAS Children's Global Assessment Scale total score
timeFrame: week 32
measure: CGAS Children's Global Assessment Scale total score - Week 60
timeFrame: week 60
Other outcomes:
Locations:
city: Toulouse
country: France
facility: Toulouse University Hospital
Study officials:
affiliation: University Hospital, Toulouse
name: Philippe Birmes, PH
role: PRINCIPAL_INVESTIGATOR
References:
citation: Olliac B, Birmes P, Bui E, Allenou C, Brunet A, Claudet I, Sales de Gauzy J, Grandjean H, Raynaud JP. Validation of the French version of the Child Post-Traumatic Stress Reaction Index: psychometric properties in French speaking school-aged children. PLoS One. 2014 Dec 2;9(12):e112603. doi: 10.1371/journal.pone.0112603. eCollection 2014.
citation: Roullet P, Vaiva G, Very E, Bourcier A, Yrondi A, Dupuch L, Lamy P, Thalamas C, Jasse L, El Hage W, Birmes P. Traumatic memory reactivation with or without propranolol for PTSD and comorbid MD symptoms: a randomised clinical trial. Neuropsychopharmacology. 2021 Aug;46(9):1643-1649. doi: 10.1038/s41386-021-00984-w. Epub 2021 Feb 21.
citation: Birmes P, Raynaud JP, Daubisse L, Brunet A, Arbus C, Klein R, Cailhol L, Allenou C, Hazane F, Grandjean H, Schmitt L. Children's enduring PTSD symptoms are related to their family's adaptability and cohesion. Community Ment Health J. 2009 Aug;45(4):290-9. doi: 10.1007/s10597-008-9166-3. Epub 2009 Jul 21.