Efficacy of Clostridium Botulinum Neurotoxin Type A Versus Placebo in Reducing Sciatic Pain in Piriformis Muscle Syndrome: A Randomized, Double-Blind Study

The primary objective of this phase IIb, randomized, double-blind, multicenter study is to evaluate, on an exploratory basis, the efficacy of a single-dose injection of **botulinum toxin** versus placebo in reducing sciatic pain intensity at 6 weeks in patients with **piriformis muscle syndrome**. This is clinically relevant as it aims to provide an alternative therapeutic option for managing pain associated with this condition, potentially improving patient outcomes and quality of life.

Secondary objectives include:

• Demonstrating the efficacy of botulinum toxin injection versus placebo in reducing buttock pain intensity at 6 weeks.
• Assessing the improvement in health-related quality of life (HR-QoL) using the EQ-5D self-report questionnaire at 6 weeks.
• Analyzing the effect of botulinum toxin injection versus placebo over a 6-month follow-up period on various parameters, including variations in sciatic and buttock pain intensity, HR-QoL, overall symptom measures, anxiety and depression, disability, tolerance of the sitting position, and consumption of analgesics, nonsteroidal anti-inflammatory drugs, and muscle relaxants.
• Comparing the number of patients requiring a second injection at 12 weeks in both arms.
• Evaluating safety and side effects in both arms.

The clinical trial involves **adult patients** aged between 18 and 80 years, diagnosed with **piriformis muscle syndrome**. Both male and female participants are included, and the study does not focus on a vulnerable population. The trial population was selected based on specific criteria, including an objective clinical diagnosis of unilateral piriformis syndrome for at least three months, confirmed by a Clinical Scoring System score of 8 or greater. Participants must not have a herniated lumbar disc that could explain radiating pain, as confirmed by MRI or CT of the lumbar spine. Additionally, they should not have responded to conventional care such as physiotherapy, muscle relaxants, or analgesics, and must report a baseline sciatic pain intensity of at least 4 points on a visual analog scale. All participants are required to provide written informed consent and be affiliated with a social security system. The sponsor has not provided information regarding the total number of participants in the study.

The clinical trial is a **phase IIb**, randomized, double-blind, multicenter study designed to evaluate the efficacy of **botulinum toxin** versus placebo in reducing pain and improving health-related quality of life in patients with **piriformis muscle syndrome**. The trial involves a single-dose injection of botulinum toxin or placebo, administered under ultrasound or CT guidance, with electromyographic confirmation. The primary objective is to assess the change in sciatic pain intensity at six weeks post-injection, measured using a visual analog scale (VAS). Secondary endpoints include changes in buttock pain intensity, health-related quality of life, physical functioning, anxiety, depression, and the need for a second injection at 12 weeks.

The trial is expected to commence recruitment on July 1, 2025, and conclude by July 1, 2028. Participants will be involved in the study for a total duration of six months, with follow-up visits scheduled at 6, 12, 18, and 24 weeks post-injection. The inclusion visit will involve screening to confirm eligibility based on criteria such as age, clinical diagnosis of piriformis muscle syndrome, and baseline sciatic pain intensity. Follow-up visits will monitor changes in pain intensity, quality of life, and any side effects of the treatment. The end-of-study visit will assess the overall outcomes and any long-term effects of the intervention.

Participants may be withdrawn from the study if they experience significant adverse effects, fail to comply with study procedures, or withdraw consent. The trial is not classified as low intervention, and the investigational product, XEOMIN, is administered intramuscularly. The placebo consists of excipients present in XEOMIN, specifically sucrose and human serum albumin. The study aims to provide valuable insights into the management of piriformis muscle syndrome, with a focus on pain reduction and quality of life improvement.

The clinical trial involves the administration of **XEOMIN**, a **botulinum toxin** formulation, specifically **Clostridium botulinum neurotoxin type A (150 kD), free of complexing proteins**. XEOMIN is provided as a powder for solution for injection, with a pharmaceutical form classified as a solution for injection. The active substance is administered via **intramuscular injection**. The maximum daily dose is 200 units, with a total maximum dose of 400 units over a treatment period of up to 3 months. The administration is performed under ultrasound guidance with electromyographic confirmation or CT guidance to ensure precision in targeting the piriformis muscle. Compliance with the dosing schedule is monitored throughout the study to ensure adherence to the protocol.

The placebo used in the study is composed solely of the excipients present in XEOMIN, specifically 4.7 mg of sucrose and 1 mg of human serum albumin per ampoule of powder for injection. The placebo is also administered via intramuscular injection, mirroring the administration route of the experimental treatment. This design ensures that any observed effects can be attributed to the active substance rather than the administration process itself. The placebo serves as a control to evaluate the efficacy of the botulinum toxin in reducing sciatic pain intensity in patients with **piriformis muscle syndrome**.

The efficacy of the clinical trial will be assessed by evaluating the change in sciatic pain intensity from baseline at 6 weeks after injection. This primary endpoint will be measured using the Visual Analog Scale (VAS), a 100mm scale where patients will report the average intensity of their pain over the last 24 hours. Secondary endpoints include changes in buttock pain intensity, also assessed on the VAS, and variations in Health-related Quality of Life (HRQoL) using the EQ-5D scale at 6 weeks and over a 6-month period. Additional secondary endpoints involve assessments of physical functioning using the Brief Pain Inventory (BPI) and Patient Global Impression of Improvement (PGI-I), anxiety and depression using the Hospital Anxiety and Depression Scale (HADS), and disability using the Oswestry Disability Index (ODI). The tolerance of the sitting position and consumption of painkillers will also be monitored. The number of patients requiring a second injection of **botulinum toxin** at 12 weeks and any side effects during follow-up will be recorded. Efficacy assessments will occur at inclusion and at 6, 12, 18, and 24 weeks post-injection.