Efficacy of Botulinum Toxin Versus Placebo on Pain and Health Related Quality of Life of Patients With Piriformis Muscle Syndrome (PiriTox)

A Phase IIb, Randomized, Double-blind, Multicenter Study Evaluating the Efficacy of Botulinum Toxin Versus Placebo on Pain and Health Related Quality of Life of Patients With Piriformis Muscle Syndrome

Piriformis muscle syndrome (PMS) is characterized by symptoms caused by compression or irritation of the sciatic nerve by the piriformis muscle as it exits the sciatic notch. PMS commonly evokes the symptoms of sciatica and is likely underdisagnosed. Patients who experience pain related to piriformis syndrome will complain of aggravated pain after prolonged periods of sitting or upon rising from a seated position. Around 98% of patients evoke positional buttock pain, especially during prolonged sitting (car journeys, for example). This is less true for sciatic pain radiation, which is still found in 63% of cases, systematically associated with the notion of buttock pain. Treatments for PMS aim to reduce or eliminate sciatic pain and also control buttock pain. Reducing these pains can improve the physical condition and emotional state of the patient. Several approaches have been proposed including physical therapy (massage-physiotherapy, self-rehabilitation techniques) combined with the use of anti-inflammatory drugs, analgesics and muscle relaxants to reduce inflammation, spasm and pain. Many patients do not respond to conventional care. Surgery may be considered only in those cases who do not improve with conservative therapy or injections. However, decompressive surgery is an invasive treatment, indicated in case of complete failure of all medical strategies, with physical and functional consequences. In recent years, several published studies showed the use of botulinum toxin (BT) injection as a new therapeutic option to reduce buttock and sciatic pain induced by PMS. The study team previously observed the efficacy of BT/A1 administration into the piriformis muscle in patients who were previously treated with medication and rehabilitation protocols with no pain improvement. Pain relief was considered as "very good" or "good" for 77% of the patients, "average" for 7.4% and "poor" for 15.6%. No adverse events were reported. More recently, Fishman and colleagues reported the results of a randomized, double-blind, controlled study including 56 patients and comparing physical therapy, incobotulinum toxin A and placebo. Data are sparse concerning BT injection for PMS and no multicenter randomized clinical trial have been performed. Two out of three randomized trials (Fishman 2004, 2017) are based on highly selected patients (3 standard deviations or more beyond on the prolongation of the posterior tibial or fibular nerve H-reflex in FAIR test). Therefore, BT efficacy may be overestimated and remains to be evaluated among unselected PMS patients, regardless of analgesic treatments or physical therapy. Finally, no randomized studies have reported the heatlh-related quality of life of PMS patients.

Study Overview

• Status: Not yet recruiting
• Conditions: Piriformis Muscle Syndrome
• Intervention / Treatment: Drug: Botulinum Toxin - A injections; Drug: Placebo

• Study Type: Interventional
• Enrollment (Estimated): 108
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Arnaud Dupeyron; Phone Number: 04.66.68.34.59; Email: arnaud.dupeyron@umontpellier.fr

Study Locations

• France
  • Besançon, France
    • CHU de Besancon
    • Contact: Fabrice MICHEL; Phone Number: 03 81 66 89 50; Email: fmichel@chu-besancon.fr
  • Bordeaux, France
    • CHU de Bordeaux
    • Contact: Mathieu DE-SEZE; Phone Number: 05.56.79.56.79; Email: mathieu.de-seze@chu-bordeaux.fr
  • Nantes, France
    • CHU de Nantes
    • Contact: Julien LABARRE; Phone Number: 02 53 48 21 87; Email: julien.labarre@chu-nantes.fr
  • Paris, France
    • Hôpital Universitaire Paris Cochin
    • Contact: François RANNOU; Phone Number: 01 58 41 23 35; Email: francois.rannou@aphp.fr
  • Strasbourg, France
    • Institut Universitaire de Réadaptation Clémenceau
    • Contact: Marie-Eve ISNER-HOROBETI; Phone Number: 03.88.21.16.39; Email: marieeve.isner@gmail.com
  • Toulouse, France
    • CHU de Toulouse
  • Gard
    • Nîmes, Gard, France, 30029
      • Centre Hospitalier Universitaire de Nimes
      • Contact: Anissa Megzarri; Phone Number: 04 66 68 68 68; Email: drc@chu-nimes.fr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Objective clinical diagnosis of unilateral piriformis syndrome for at least 3 months (as assessed by Clinical Scoring System for the Diagnosis of Piriformis Muscle Syndrome: score of 8 or greater
• Absence of herniated lumbar disc which can explain radiating pain (MRI or computed tomography (CT) of the lumbar spine)
• Patients not responding to conventional care (physiotherapy, muscle relaxants, analgesics)
• Baseline sciatic pain intensity of at least 4 points on visual analog scale
• Provision of written informed consent
• Patients affiliated to social security system (health insurance coverage).

Exclusion Criteria:

• Bilateral piriformis muscle syndrome.
• History of piriformis syndrome surgery.
• History of botulinum toxin administration.
• Any treatment (general or local) likely to interfere with botulinum toxin or evaluation of the primary endpoint (Corticosteroids, aminoglycosides).
• Corticosteroids in the past 3 weeks.
• Signs of severe fibrosis (on MRI or CT) of the piriformis muscle.
• Other causes of sciatic pain (lumbar root compression, inflammatory, infectious or neoplasic pelvic disease, particularly for inflammatory sacroiliac pain).
• Hip prosthesis on the same side as piriformis syndrome; knee prosthesis is tolerated.
• Contraindication to BT injection:
• History of intolerance, hypersensitivity or known allergy to any botulinum toxin product or excipients;
• Patients with myasthenia gravis or other diseases of the neuromuscular junction;
• Patients with Lambert-Eaton Syndrome;
• Patients with neurological disorders such as dysphagia, swallowing disorders or aspiration pneumonia;
• Current infection at the proposed injection site;
• Long-term anticoagulant therapy ;
• Antibiotics and vaccination are prohibited for 15 days before and after BT injection
• Pregnant or breastfeeding women. Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant must use an effective method of contraception (oral contraceptives, contraceptive injections, intrauterine devices, method of double-barrier contraceptive patches). The contraception should be maintained throughout the study.
• Patients unable to complete the patient diary.
• Inability to understand the reasons for the study; psychiatric disorders judged by the investigator to be incompatible with inclusion in the study.
• Patients with legal disability or limited legal capacity.
• Patients judged as noncompliant.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Botulinum toxin injection	Drug: Botulinum Toxin - A injections; Incobotulinumtoxin type A (200 U in 2 mL of preservative-free normal saline) will be injected in equally divided doses (1mL; 100 U for incobotulinumtoxin A) into 2 locations in the affected buttock region
Placebo Comparator: Placebo injection	Drug: Placebo; Placebo (normal saline solution and excipients described in Xeomin) will be injected in equally divided doses (1mL) into 2 locations in the affected buttock region

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in sciatic pain	Measured on a 0 (no pain) to 10 (worst pain) visual analog scale	From baseline to Week 6

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in buttock pain intensity	Measured on a 0 (no pain) to 10 (worst pain) visual analog scale	From baseline to Week 6
Health-related quality of life	EuroQol-5 Dimension questionnaire measuring five items representing the five dimensions, and a visual analog scale graduated from 0 to 100 (100 referring to the "best possible state of health"). For each dimension, patients indicate their current state of health to generated a 5-digit number describing the health status (e.g., health status "11111" indicates the absence of problems in each dimension)	Baseline
Health-related quality of life	EuroQol-5 Dimension questionnaire measuring five items representing the five dimensions, and a visual analog scale graduated from 0 to 100 (100 referring to the "best possible state of health"). For each dimension, patients indicate their current state of health to generated a 5-digit number describing the health status (e.g., health status "11111" indicates the absence of problems in each dimension)	Week 6
Health-related quality of life	EuroQol-5 Dimension questionnaire measuring five items representing the five dimensions, and a visual analog scale graduated from 0 to 100 (100 referring to the "best possible state of health"). For each dimension, patients indicate their current state of health to generated a 5-digit number describing the health status (e.g., health status "11111" indicates the absence of problems in each dimension)	Week 12
Health-related quality of life	EuroQol-5 Dimension questionnaire measuring five items representing the five dimensions, and a visual analog scale graduated from 0 to 100 (100 referring to the "best possible state of health"). For each dimension, patients indicate their current state of health to generated a 5-digit number describing the health status (e.g., health status "11111" indicates the absence of problems in each dimension)	Week 18
Health-related quality of life	EuroQol-5 Dimension questionnaire measuring five items representing the five dimensions, and a visual analog scale graduated from 0 to 100 (100 referring to the "best possible state of health"). For each dimension, patients indicate their current state of health to generated a 5-digit number describing the health status (e.g., health status "11111" indicates the absence of problems in each dimension)	Week 24
Sciatic pain intensity	Assessed on Visual Analog Scale value (0 = no pain, 10 = worst pain)	Baseline
Sciatic pain intensity	Assessed on Visual Analog Scale value (0 = no pain, 10 = worst pain)	Week 3
Sciatic pain intensity	Assessed on Visual Analog Scale value (0 = no pain, 10 = worst pain)	Week 6
Sciatic pain intensity	Assessed on Visual Analog Scale value (0 = no pain, 10 = worst pain)	Week 9
Sciatic pain intensity	Assessed on Visual Analog Scale value (0 = no pain, 10 = worst pain)	Week 12
Sciatic pain intensity	Assessed on Visual Analog Scale value (0 = no pain, 10 = worst pain)	Week 15
Sciatic pain intensity	Assessed on Visual Analog Scale value (0 = no pain, 10 = worst pain)	Week 18
Sciatic pain intensity	Assessed on Visual Analog Scale value (0 = no pain, 10 = worst pain)	Week 21
Sciatic pain intensity	Assessed on Visual Analog Scale value (0 = no pain, 10 = worst pain)	Week 24
Buttock pain intensity	Assessed on Visual Analog Scale value (0 = no pain, 10 = worst pain)	Baseline
Buttock pain intensity	Assessed on Visual Analog Scale value (0 = no pain, 10 = worst pain)	Week 3
Buttock pain intensity	Assessed on Visual Analog Scale value (0 = no pain, 10 = worst pain)	Week 6
Buttock pain intensity	Assessed on Visual Analog Scale value (0 = no pain, 10 = worst pain)	Week 9
Buttock pain intensity	Assessed on Visual Analog Scale value (0 = no pain, 10 = worst pain)	Week 12
Buttock pain intensity	Assessed on Visual Analog Scale value (0 = no pain, 10 = worst pain)	Week 15
Buttock pain intensity	Assessed on Visual Analog Scale value (0 = no pain, 10 = worst pain)	Week 18
Buttock pain intensity	Assessed on Visual Analog Scale value (0 = no pain, 10 = worst pain)	Week 21
Buttock pain intensity	Assessed on Visual Analog Scale value (0 = no pain, 10 = worst pain)	Week 24
Physical functioning	Brief Pain Inventory Short Form; 9-item questionnaire, where Worst Pain Score: 1 - 4 = Mild Pain; Worst Pain Score: 5 - 6 = Moderate Pain; Worst Pain Score: 7 - 10 = Severe Pain	Baseline
Physical functioning	Brief Pain Inventory Short Form; 9-item questionnaire, where Worst Pain Score: 1 - 4 = Mild Pain; Worst Pain Score: 5 - 6 = Moderate Pain; Worst Pain Score: 7 - 10 = Severe Pain	Week 6
Physical functioning	Brief Pain Inventory Short Form; 9-item questionnaire, where Worst Pain Score: 1 - 4 = Mild Pain; Worst Pain Score: 5 - 6 = Moderate Pain; Worst Pain Score: 7 - 10 = Severe Pain	Week 12
Physical functioning	Brief Pain Inventory Short Form; 9-item questionnaire, where Worst Pain Score: 1 - 4 = Mild Pain; Worst Pain Score: 5 - 6 = Moderate Pain; Worst Pain Score: 7 - 10 = Severe Pain	Week 18
Physical functioning	Brief Pain Inventory Short Form; 9-item questionnaire, where Worst Pain Score: 1 - 4 = Mild Pain; Worst Pain Score: 5 - 6 = Moderate Pain; Worst Pain Score: 7 - 10 = Severe Pain	Week 24
Perceived change in condition in response to therapy	Patient Global Impression of Improvement (PGI-I)	Baseline
Perceived change in condition in response to therapy	Patient Global Impression of Improvement (PGI-I)	Week 6
Perceived change in condition in response to therapy	Patient Global Impression of Improvement (PGI-I)	Week 12
Perceived change in condition in response to therapy	Patient Global Impression of Improvement (PGI-I)	Week 18
Perceived change in condition in response to therapy	Patient Global Impression of Improvement (PGI-I)	Week 24
Emotional distress	Hospital Anxiety and Depression Scale (HADS); 14 items, with responses scored on a scale of 0-3 (3 indicates higher symptom frequencies). Subscales (anxiety and depression) range from 0 to 21 whereby: normal 0-7, mild 8-10, moderate 11-14, and severe 15-21.	Baseline
Emotional distress	Hospital Anxiety and Depression Scale (HADS); 14 items, with responses scored on a scale of 0-3 (3 indicates higher symptom frequencies). Subscales (anxiety and depression) range from 0 to 21 whereby: normal 0-7, mild 8-10, moderate 11-14, and severe 15-21.	Week 6
Emotional distress	Hospital Anxiety and Depression Scale (HADS); 14 items, with responses scored on a scale of 0-3 (3 indicates higher symptom frequencies). Subscales (anxiety and depression) range from 0 to 21 whereby: normal 0-7, mild 8-10, moderate 11-14, and severe 15-21.	Week 12
Emotional distress	Hospital Anxiety and Depression Scale (HADS); 14 items, with responses scored on a scale of 0-3 (3 indicates higher symptom frequencies). Subscales (anxiety and depression) range from 0 to 21 whereby: normal 0-7, mild 8-10, moderate 11-14, and severe 15-21.	Week 18
Emotional distress	Hospital Anxiety and Depression Scale (HADS); 14 items, with responses scored on a scale of 0-3 (3 indicates higher symptom frequencies). Subscales (anxiety and depression) range from 0 to 21 whereby: normal 0-7, mild 8-10, moderate 11-14, and severe 15-21.	Week 24
Disability for low back pain	Oswestry Disability Index (ODI): range 0 to 100. Zero is equated with no disability and 100 is the maximum disability possible.	Baseline
Disability for low back pain	Oswestry Disability Index (ODI): range 0 to 100. Zero is equated with no disability and 100 is the maximum disability possible.	Week 6
Disability for low back pain	Oswestry Disability Index (ODI): range 0 to 100. Zero is equated with no disability and 100 is the maximum disability possible.	Week 12
Disability for low back pain	Oswestry Disability Index (ODI): range 0 to 100. Zero is equated with no disability and 100 is the maximum disability possible.	Week 18
Disability for low back pain	Oswestry Disability Index (ODI): range 0 to 100. Zero is equated with no disability and 100 is the maximum disability possible.	Week 24
Tolerance of the sitting position	Time between the beginning of the sitting position and the onset or worsening of the pain	Baseline
Tolerance of the sitting position	Time between the beginning of the sitting position and the onset or worsening of the pain	Week 6
Tolerance of the sitting position	Time between the beginning of the sitting position and the onset or worsening of the pain	Week 12
Tolerance of the sitting position	Time between the beginning of the sitting position and the onset or worsening of the pain	Week 18
Tolerance of the sitting position	Time between the beginning of the sitting position and the onset or worsening of the pain	Week 24
Consumption of painkillers	Number of level 1 to 3 analgesics, non-steroidal anti-inflammatory drugs and muscle relaxants	Week 24
Number of patients requiring a second injection botulinum toxin in each arm	Number	Week 12
Side effects of injection	Side effects of the injection or attributable to the study drug	Week 24

Collaborators and Investigators

• Sponsor: Centre Hospitalier Universitaire de Nīmes
• Investigators: Principal Investigator: Arnaud Dupeyron, CHU Nîmes

Study record dates

Study Major Dates

• Study Start (Estimated): July 1, 2026
• Primary Completion (Estimated): January 1, 2029
• Study Completion (Estimated): January 1, 2029

Study Registration Dates

• First Submitted: May 29, 2026
• First Submitted That Met QC Criteria: May 29, 2026
• First Posted (Actual): June 3, 2026

Study Record Updates

• Last Update Posted (Actual): June 3, 2026
• Last Update Submitted That Met QC Criteria: May 29, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pain; Neurologic Manifestations; Nervous System Diseases; Neuromuscular Diseases; Peripheral Nervous System Diseases; Neuralgia; Pelvic Pain; Mononeuropathies; Nerve Compression Syndromes; Sciatic Neuropathy; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Piriformis Muscle Syndrome
• Other Study ID Numbers: PHRCN/2019/AD-1; 2024-517948-66-00 (Ctis)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No