Treatment of Pediatric Post-traumatic Stress Disorder With Memory Reactivation Under the Influence of Propranolol

NCT ID: NCT04985344

Last Updated: 2023-08-28

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE3
• Total Enrollment: 92 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-02-01
• Study Completion Date: 2027-09-30

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

Conditions

PTSD

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Propranolol

Patient will receive oral propranolol

Group Type: EXPERIMENTAL

Propranolol Oral Product

Intervention Type: DRUG

Child will receive oral propranolol (syrup). The dose of propranolol will increase gradually over the first 3 treatment sessions in order to assess tolerance.

memory reactivation

Intervention Type: OTHER

90 minutes after the propranolol take, a trained psychologist will ask the child to recount his trauma.

Placebo

Patient will receive oral placebo

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Child will receive oral placebo (syrup). The dose of placebo will increase gradually over the first 3 treatment sessions in order to match propranolol intervention.

memory reactivation

Intervention Type: OTHER

90 minutes after the propranolol take, a trained psychologist will ask the child to recount his trauma.

Interventions

Propranolol Oral Product

Child will receive oral propranolol (syrup). The dose of propranolol will increase gradually over the first 3 treatment sessions in order to assess tolerance.

Intervention Type: DRUG

Placebo

Child will receive oral placebo (syrup). The dose of placebo will increase gradually over the first 3 treatment sessions in order to match propranolol intervention.

Intervention Type: DRUG

memory reactivation

90 minutes after the propranolol take, a trained psychologist will ask the child to recount his trauma.

Intervention Type: OTHER

Other Intervention Names

Propranolol

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

• Minimum Eligible Age: 7 Years
• Maximum Eligible Age: 12 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University Hospital, Toulouse

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Philippe Birmes, PH

Role: PRINCIPAL_INVESTIGATOR

University Hospital, Toulouse

Locations

Toulouse University Hospital

Toulouse, , France

Site Status: RECRUITING

Countries

France

Central Contacts

Philippe Birmes, PH

Role: CONTACT

birmes.p@chu-toulouse.fr

05 34 55 75 00 ext. +33

Facility Contacts

Philippe BIRMES, PH

Role: primary

birmes.p@chu-toulouse.fr

5 34 55 75 00 ext. +33

References

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.

Reference Type: BACKGROUND

PMID: 25460912 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 33612830 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 19621258 (View on PubMed)

Other Identifiers

2020-005956-39

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

RC31/18/0471

Identifier Type: -

Identifier Source: org_study_id