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

NCT04985344 | Recruiting Phase 3

• 2 other identifiers: RC31/18/04712020-005956-39
• Study Type: interventional
• Target: 92
• Locations: 1 country
• Sites: 1

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.

Conditions

PTSD

Keywords

PTSD; traumatic memory reactivation; pediatric; Propranolol; Post-traumatic stress disorder

Outcome Measures

Primary Outcomes (1)

• Child Post-Traumatic Stress Reaction Index/CPTS-RI

  The main evaluation criterion will be the difference between the Child Post-Traumatic Stress Reaction Index/CPTS-RI total score administered at week 8 and week 0. The CPTS-RI is a scale comprised of 20 Likert-type items, intended for children from 6 to 16 years, which evaluates the symptoms of PTSD after exposure to various traumatic events. Each item frequency is rated on a 5-point scale, from never (=0) to almost always (=4). The global score consists of the sum of the 20 items and ranges from 0 to 80, with higher scores indicating higher PTSD symptom severity. The time required for completion of the scale is 15-20 min. A total score of 12-24 is associated with a mild level of PTSD, from 25-39 with a moderate level, from 40-59 with a severe level, and ≥60 with a very severe level.

  week 8

Secondary Outcomes (20)

• Child Post-Traumatic Stress Reaction - Week 32 Index/CPTS-RI

  week 32

• Child Post-Traumatic Stress Reaction - Week 60 Index/CPTS-RI

  week 60

• Child PTSD Checklist-Child version/CPC-C total score

  Week 8

• Child PTSD Checklist-Child version/CPC-C total score - Week 32

  Week 32

• Child PTSD Checklist-Child version/CPC-C total score - Week 60

  Week 60

Study Arms (2)

Propranolol

EXPERIMENTAL

Patient will receive oral propranolol

Drug: Propranolol Oral Product; Other: memory reactivation

Placebo

PLACEBO COMPARATOR

Patient will receive oral placebo

Drug: Placebo; Other: memory reactivation

Interventions

Propranolol Oral Product 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.

Also known as: Propranolol

Propranolol

Placebo 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.

Placebo

memory reactivation OTHER

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

Placebo; Propranolol

Eligibility Criteria

• Age: 7 Years - 12 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University Hospital, Toulouse: lead

Study Sites (1)

Toulouse University Hospital

Toulouse, 31059, France

RECRUITING

Related Publications (3)

• 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.

  PMID: 25460912 BACKGROUND

• 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.

  PMID: 33612830 BACKGROUND

• 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.

  PMID: 19621258 BACKGROUND

MeSH Terms

Conditions

Stress Disorders, Post-Traumatic

Interventions

Propranolol

Condition Hierarchy (Ancestors)

Stress Disorders, Traumatic; Trauma and Stressor Related Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Phenoxypropanolamines; Propanolamines; Amino Alcohols; Alcohols; Organic Chemicals; Propanols; Amines; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Polycyclic Compounds

Study Officials

• Philippe Birmes, PH

  University Hospital, Toulouse

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Philippe Birmes, PH

CONTACT

05 34 55 75 00; birmes.p@chu-toulouse.fr

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 21, 2021
• First Posted: August 2, 2021
• Study Start: February 1, 2023
• Primary Completion (Estimated): September 1, 2027
• Study Completion (Estimated): September 1, 2027
• Last Updated: August 28, 2023

Record last verified: 2023-08

Data Sharing

• IPD Sharing: Will not share

Locations

FR (1)