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

Official title

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

Overview

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.

Interventions

• 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
• 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

Primary outcome measures

• Change in sciatic pain [Time frame: From baseline to Week 6]

Secondary outcome measures (12)

• Change in buttock pain intensity [Time frame: From baseline to Week 6]
• Health-related quality of life [Time frame: Baseline]
• Health-related quality of life [Time frame: Week 6]
• Health-related quality of life [Time frame: Week 12]
• Health-related quality of life [Time frame: Week 18]
• Health-related quality of life [Time frame: Week 24]
• Sciatic pain intensity [Time frame: Baseline]
• Sciatic pain intensity [Time frame: Week 3]
• Sciatic pain intensity [Time frame: Week 6]
• Sciatic pain intensity [Time frame: Week 9]
• Sciatic pain intensity [Time frame: Week 12]
• Sciatic pain intensity [Time frame: Week 15]

Eligibility criteria

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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Triple blind

Primary purpose

Treatment

Study locations

France · 7 centers

• Centre Hospitalier Universitaire de Nîmes — Nîmes
• CHU de Besançon — Besançon
• CHU de Bordeaux — Bordeaux
• CHU de Nantes — Nantes
• Hôpital Universitaire Paris Cochin — Paris
• Institut Universitaire de Réadaptation Clémenceau — Strasbourg
• CHU de Toulouse — Toulouse

Identifiers

NCT: NCT07624045 · PHRCN/2019/AD-1 · 2024-517948-66-00

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗