Evaluation of Propranolol for Early Secondary Prevention of Post-Traumatic Stress Disorder in Adult Female Victims of Sexual Violence: A Randomized, Placebo-Controlled Pilot Study

The primary objective of this study is to evaluate the effect of early administration of **Propranolol** on the occurrence of symptoms of post-traumatic stress disorder (PTSD) at five weeks in adult female victims of sexual violence. This is clinically relevant as it aims to assess the potential of Propranolol as a preventive intervention for PTSD, which could significantly impact the management and outcomes for this vulnerable population.

Secondary objectives include:

• Evaluating the effect of early Propranolol administration on the intensity of PTSD symptoms at five weeks.
• Assessing the occurrence and intensity of PTSD symptoms at three and six months.
• Evaluating the impact on healthcare utilization, work absenteeism, and associated costs at three months.
• Assessing the tolerance of Propranolol in this context.

The clinical trial focuses on the **prevention of post-traumatic stress disorder** and involves a study population exclusively composed of adult females, specifically those who are cisgender. Participants are required to be 18 years of age or older and must have a heart rate of at least 55 bpm. The trial does not include a vulnerable population. Participants must be able to understand and read French, and they are required to have been seen in a sexual violence consultation within 72 hours of the incident. Additionally, participants must be affiliated with a social security system and provide written informed consent. The sponsor has not provided information regarding the total number of participants in the study. Lifestyle considerations such as diet and physical activity are not specified, but participants must agree to follow contraceptive requirements as detailed in the protocol. The selection process for the trial population is not detailed beyond the inclusion criteria provided.

The clinical trial is designed as a **randomized**, **placebo-controlled** study to evaluate the effect of early **Propranolol** intake on the prevention of post-traumatic stress disorder (PTSD) symptoms in adult female victims of sexual violence. The trial will be conducted over a period of approximately two years, with an estimated recruitment start date in January 2025 and an estimated end date in January 2027. Participants will be randomly assigned to receive either Propranolol 40 mg film-coated tablets or a placebo, administered orally. The trial is structured to include several key visits: an initial screening visit, follow-up visits at five weeks, three months, and six months, and an end-of-study visit.

The screening visit will determine eligibility based on criteria such as age, heart rate, and language proficiency, among others. Participants must provide informed consent and meet all inclusion criteria to be enrolled. The primary endpoint is the rate of participants presenting PTSD symptoms at five weeks, assessed using the CAPS-5 scale. Secondary endpoints include evaluations of PTSD symptomatology and individual functioning at five weeks, three months, and six months, using various self-questionnaires. Adverse events will be monitored throughout the study.

Participants are expected to be involved in the study for a maximum of 24 weeks, with the possibility of early termination if they fail to adhere to the study protocol, experience significant adverse effects, or withdraw consent. The trial is categorized as a Phase 4 study, focusing on the secondary prevention of PTSD symptoms. The study aims to provide valuable insights into the potential benefits of Propranolol in this context, contributing to the broader understanding of PTSD management.

The clinical trial involves the administration of **Propranolol**, a non-selective beta-adrenergic receptor blocker, formulated as 40 mg film-coated tablets. The pharmaceutical form is designed for **oral use**. The maximum daily dose is set at 120 mg, with a total maximum dose of 2040 mg over the course of the study. The treatment period is limited to a maximum of 24 weeks. The medication is manufactured by IPCA Productos Farmaceuticos Unipessoal LDA and is identified by the marketing authorization number 5866363. The active substance, propranolol, is of chemical origin and is classified under the ATC code C07AA05. Participants are required to adhere to the dosing schedule as prescribed, and compliance will be monitored throughout the trial.

The study also includes a **placebo** control, which consists of microcrystalline cellulose. This substance is used as an inert comparator to evaluate the efficacy of the experimental treatment. The placebo is administered in a manner consistent with the experimental medication to maintain blinding and ensure the integrity of the study results. The placebo does not contain any active pharmaceutical ingredients and serves solely as a control to assess the therapeutic effects of propranolol.

Efficacy in this clinical trial will be assessed primarily by evaluating the rate of participants presenting with symptoms of **Post-Traumatic Stress Disorder (PTSD)**. This assessment will be conducted at five weeks using the CAPS-5 (Clinician Administered PTSD Scale for DSM-5) by a healthcare professional from the Regional Psychotraumatology Center. Secondary endpoints include evaluating PTSD symptomatology and the impact on individual functioning at various timepoints. At five weeks, self-questionnaires such as the IES-R (Impact of Event Scale – Revised), PCL-5 (Posttraumatic Stress Disorder Checklist for DSM-5), and PHQ-9 (Patient Health Questionnaire) will be used to assess PTSD symptoms. The impact on individual functioning will be measured using the FAST (Functional Assessment Staging Tool), GAF (Global Assessment of Functioning), and a subjective Visual Analog Scale (VAS) of health status. These assessments will be repeated at three and six months, with additional evaluations of healthcare costs, work stoppages, and suicide risk using the C-SSRS scale at three months. Adverse events will be collected throughout the study duration. The trial is designed to determine the effect of early Propranolol intake on the occurrence of PTSD symptoms in adult female victims of sexual violence.