Evaluation of the effectiveness of the reconsolidation therapy in a clinical population suffering from post-traumatic stress disorder

The primary objective of this study is to verify the effectiveness of **reconsolidation therapy** in patients with a chronic and severe form of **post-traumatic stress disorder** (PTSD) requiring hospital care. This is clinically relevant as it aims to compare reconsolidation therapy to prolonged exposure therapy, which is recommended by established guidelines, and to the standard therapy offered within psychiatric care units. Additionally, the study seeks to determine if **propranolol** facilitates the extinction of fear conditioning by comparing a therapeutic group receiving prolonged exposure therapy plus propranolol to a group receiving prolonged exposure therapy without propranolol.

Secondary objectives include:

• Assessing the benefits of reconsolidation therapy on symptoms commonly associated with PTSD, such as anxiety, depression, emotional vulnerability, and emotional regulation skills.
• Evaluating different treatments through the physiological index of heart rate variability (HRV), a biomarker for the autonomic nervous system, to determine if effective treatment alleviates symptoms of hyperreactivity and reliving, thereby elevating the HRV index.
• Testing the hypothesis that therapies offering propranolol will facilitate trauma work by making it more bearable due to its regulatory action on the overactivation of the sympathetic nervous system during reevocation or exposure sessions, compared to the group receiving prolonged exposure therapy and a control group.

The clinical trial focuses on individuals diagnosed with **post-traumatic stress disorder** (PTSD), specifically targeting a population aged 18 to 65 years. Both male and female participants are included, with no specific emphasis on a vulnerable population. Participants are required to be hospitalized in a psychiatric care unit and must be French-speaking. The study encompasses individuals with PTSD who exhibit behavioral disorders such as emotional regulation difficulties, impulsivity, interpersonal challenges, chronic feelings of emptiness and abandonment, and dissociative symptoms. Women of childbearing potential are required to use hormonal contraception or a non-hormonal intrauterine device, with a negative high sensitivity pregnancy test as a prerequisite for inclusion. The sponsor has not provided information regarding the total number of participants in the trial. The selection criteria ensure a focus on those with a chronic and severe form of PTSD, necessitating hospital care, and the trial does not impose specific lifestyle considerations such as diet or physical activity.

The clinical trial is designed to evaluate the effectiveness of reconsolidation therapy in patients diagnosed with **post-traumatic stress disorder** (PTSD). This study is a Phase 4, randomized, double-blind, controlled trial comparing reconsolidation therapy to prolonged exposure therapy, with and without the administration of **propranolol hydrochloride**. The trial aims to determine if propranolol facilitates the extinction of fear conditioning. The trial is expected to run from February 2023 to February 2029, with participant involvement lasting up to six months.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as age (18-65 years), hospitalization in a psychiatric care unit, and a diagnosis of PTSD. Women of childbearing potential must use effective contraception and have a negative pregnancy test before inclusion. Follow-up visits will occur regularly to monitor the participants' progress and assess the primary endpoint using the Posttraumatic Stress Disorder Checklist Scale (PCL-S). Secondary endpoints include the Positive and Negative Affect Schedule (PANAS), Hospital Anxiety and Depression Scale (HADs), Difficulties in Emotion Regulation Scale (DERS), and heart rate variability measurements.

The end-of-study visit will conclude the participant's involvement, during which final assessments will be conducted. Participants may be withdrawn from the study early if they experience adverse effects, fail to comply with the study protocol, or withdraw consent. The trial will utilize **Inderal** 10 mg and 40 mg film-coated tablets, administered orally, with a maximum daily dose of 80 mg and a total dose not exceeding 960 mg over the treatment period. The study is not classified as low intervention and involves authorized medical products, ensuring adherence to rigorous scientific and ethical standards.

The clinical trial involves the administration of **Inderal 10 mg film-coated tablets**, which contain the active substance **propranolol hydrochloride**. This medication is provided in the form of film-coated tablets and is intended for **oral use**. The maximum daily dose for this formulation is 30 mg, with a total maximum dose of 360 mg over the course of the treatment. The treatment period is set for a maximum of 6 weeks. The propranolol hydrochloride used in this trial is of chemical origin, and the product is manufactured by Atnahs Pharma UK Limited. Participant compliance with the dosing schedule will be monitored throughout the trial.

Additionally, the trial includes the use of **Inderal 40 mg film-coated tablets**, also containing **propranolol hydrochloride**. Similar to the 10 mg formulation, these tablets are designed for **oral use**. The maximum daily dose for the 40 mg tablets is 80 mg, with a total maximum dose of 960 mg over the treatment period, which is also capped at 6 weeks. This formulation is likewise produced by Atnahs Pharma UK Limited, and the active substance is of chemical origin. Compliance with the prescribed dosing regimen will be closely monitored to ensure adherence to the study protocol.

In this clinical trial, propranolol is being evaluated for its potential role as a facilitator of extinction in fear conditioning, in conjunction with prolonged exposure therapy for patients with post-traumatic stress disorder (PTSD). The study aims to compare the effectiveness of reconsolidation therapy with prolonged exposure therapy, both with and without the addition of propranolol, to determine its impact on treatment outcomes.

The efficacy of the clinical trial evaluating the effectiveness of reconsolidation therapy in patients with **post-traumatic stress disorder** (PTSD) will be assessed using both primary and secondary endpoints. The primary endpoint is the Posttraumatic Stress Disorder Checklist Scale (PCL-S), which will be used to measure symptom severity and improvement. Secondary endpoints include the Positive And Negative Affect Schedule (PANAS), the Hospital Anxiety and Depression Scale (HADs), the Difficulties in Emotion Regulation Scale (DERS), and Heart Rate Variability (HRV) measured by a Polar V800 device. These endpoints will provide a comprehensive evaluation of the therapy's impact on emotional regulation, anxiety, depression, and physiological responses.

The trial will compare the efficacy of reconsolidation therapy to prolonged exposure therapy, both with and without the addition of **propranolol hydrochloride**. The inclusion of propranolol aims to assess its potential role in facilitating the extinction of fear conditioning. The trial is designed to include patients aged 18 to 65 who are hospitalized in a psychiatric care unit and diagnosed with PTSD. The study will follow a structured methodology to ensure accurate and reliable data collection and analysis, adhering to established guidelines and validated scales for measuring the specified endpoints.