E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Post-traumatic Stress Disorder |
Stress post traumatique |
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E.1.1.1 | Medical condition in easily understood language |
Post-traumatic Stress Disorder |
Stress post traumatique |
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E.1.1.2 | Therapeutic area | Psychiatry and Psychology [F] - Mental Disorders [F03] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | HLT |
E.1.2 | Classification code | 10042211 |
E.1.2 | Term | Stress disorders |
E.1.2 | System Organ Class | 100000004873 |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To examine the efficacy of oral propranolol (0.66 mg/Kg to 1 mg/Kg vs. placebo) administered 90’ prior to six weekly sessions of traumatic memory reactivation in reducing self-reported PTSD symptom severity in children (aged 7-12) with long lasting PTSD (≥6 months) at endpoint (1-week post-treatment=1 week after the 6th and last treatment session) |
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E.2.2 | Secondary objectives of the trial |
-To examine the efficacy of propranolol (vs. placebo) administered prior to six weekly sessions of traumatic memory reactivation in reducing parent-reported PTSD symptom severity in children with PTSD aged 7-12 at endpoint
-To examine the efficacy of propranolol (vs. placebo) administered prior to six weekly sessions of traumatic memory reactivation in reducing rates of PTSD in children with PTSD aged 7-12 at endpoint
-To examine the efficacy of propranolol (vs. placebo) administered prior to six weekly sessions of traumatic memory reactivation in reducing self-reported major depressive episode symptom severity in children with PTSD aged 7-12 at endpoint
-To examine the efficacy of propranolol (vs. placebo) administered prior to six weekly sessions of traumatic memory reactivation on all outcomes at 6- month follow-up
-To examine the efficacy of propranolol (vs. placebo) administered prior to six weekly sessions of traumatic memory reactivation on all outcomes at 1-year follow-up
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
-Children aged 7-12 years
-CPTS-RI total score ≥40
-Primary diagnosis of PTSD (6 months or more after the traumatic event)
-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
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E.4 | Principal exclusion criteria |
-Age<7 years or ≥13 years
-Child or parents that don’t have a good understanding of the French language according to investigator's opinion
- 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)., greater than first-degree heart block, heart failure, bronchial asthma and hypersensitivity to propranolol hydrochloride)
-Heart Rate/HR<50 bpm
-Concurrent medication with possible interactions with propranolol
--Concurrent psychotropic drugs that have been shown to be effective in improving symptoms of PTSD
-Concurrent psychotherapy (>1 stuctured 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
-Pregnancy
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E.5 End points |
E.5.1 | Primary end point(s) |
The main evaluation criterion will be the difference between the Child Post-Traumatic Stress Reaction Index/CPTS-RI total score administered at week 0 before the first treatment session and the CPTS-RI total score administered at week 8 (study endpoint=one week after the sixth and last treatment session). |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
The difference between the Child PTSD Checklist-Child version/CPC-C total score on items 14-34 (PTSD symptom items) administered at week 0 before the first treatment session and the CPC-C total score on items 14-34 administered at week 8 (study endpoint).
The difference between the Child PTSD Checklist-Parent version/CPC-P total score on items 14-34 (PTSD symptom items) administered at week 0 before the first treatment session and the CPC-P total score on items 14-34 administered at week 8 (study endpoint).
The percentage of children without a current diagnosis of PTSD at week 8 (study endpoint) one week after the sixth and last treatment session. A current diagnosis of PTSD will be assessed by the semi-structured diagnosis interview Kiddie-SADS-Present and Lifetime Version DSM-5/K-SADS-PL-DSM5 at study endpoint.
The difference between the Children Depression Inventory/CDI total score administered at week 0 before the first treatment session and the CDI total score at week 8 (study endpoint) one week after the sixth and last treatment session.
The difference between the Children’s Sleep Habits Questionnaire/CSHQ Parent version total score administered at week 0 before the first treatment session and the CSHQ total score at week 8 (study endpoint) one week after the sixth and last treatment session.
The difference between the CPTS-RI total score administered at week 8 and the CPTS-RI total score administered at week 32 (6 months after the sixth and last treatment session), and at week 60 (1 year after the sixth and last treatment session). The difference between the CPC-C total score on items 14-34 (PTSD symptom items) administered at week 8 and the CPC-C total score on items 14-34 administered at week 32 (6 months after the sixth and last treatment session), and at week 60 (1 year after the sixth and last treatment session).
The difference between the CPC-P total score on items 14-34 (PTSD symptom items) administered at week 8 and the CPC-P total score on items 14-34 administered at week 32 (6 months after the sixth and last treatment session), and at week 60 (1 year after the sixth and last treatment session).
The percentage of children without a current diagnosis of PTSD at week 32 (6 months after the sixth and last treatment session), and at week 60 (1 year after the sixth and last treatment session).
The difference between the CDI total score administered at week 8 and the CDI total score administered at week 32 (6 months after the sixth and last treatment session), and at week 60 (1 year after the sixth and last treatment session).
The difference between the CSHQ total score administered at week 8 and the CSHQ total score administered at week 32 (6 months after the sixth and last treatment session), and at week 60 (1 year after the sixth and last treatment session).
The comorbidity of other mental disorders will be assessed using the K-SADS-PL DSM-5.
The difference between the Corsi Blocks task administered at week 0 and the Corsi Blocks task administered at week 8.
The description, through general inquiry, of potential side effects and health issues which could occur during the study in order to evaluate propranolol’s safety profile. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | No |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 4 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 3 |
E.8.9.1 | In the Member State concerned months | 8 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 8 |