A Phase III Study to Evaluate Efficacy of Botulinum Toxin for Treating Epicondylitis (EPITOX)

A Phase III Randomized Double-blind Study to Evaluate Efficacy of Botulinum Toxin for Treating Epicondylitis

The study aims to demonstrate that intramuscular injection of botulinum toxin with a paralyzing dose coupled with subcutaneous injection of corticoid has greater efficacy than corticoid injection only or toxin injection only for treating lateral epicondylitis in reducing pain at 6 months.

As secondary objectives, the study aims to

• demonstrate improvement of quality of patient's life and positive effect on their resuming to professional activities or sportive activities.
• evaluate tolerance of treatment by grip strength measurement and adverse event collection.

Study Overview

• Status: Completed
• Conditions: Epicondylitis
• Intervention / Treatment: Drug: Injection, botulinum toxin + corticoid; Drug: Injection, placebo of toxin + corticoid; Drug: Injection, botulinum toxin + placebo corticoid

Detailed Description

This is a prospective multicenter phase IIIb randomized double-blind placebo-controlled study, to compare efficacy and tolerance of 3 groups of treatments for epicondylitis.

All patients will be randomized in 3 following parallel treatment groups:

Group A : botulinum toxin + corticoid

Group C : placebo of toxin + corticoid

Group T : botulinum toxin + placebo corticoid

The study will be performed in 4 centers in France, targetting 150 patients. The follow-up of each patient will last 6 months after treatment.

• Study Type: Interventional
• Enrollment (Actual): 33
• Phase: Phase 3

Contacts and Locations

Study Locations

• France
  • Hauts-de-Seine
    • Garches, Hauts-de-Seine, France, 92380
      • Service de Médecine Physique et de Réadaptation, Hôpital Raymond Poincaré

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Patient aged between 18 and 60 years;
• Physical disability or not;
• Unilateral lateral epicondylitis more than 3 months, recurrent or not, no response to at least one standard treatment such as: local injection of corticoid, physiotherapy, rest, NSAIDs per os;
• Signed consent obtained;
• Covered by health insurance.

Exclusion Criteria:

• Central nervous system disorders result in spasticity in epicondylitis limb;
• History of severe psychiatric disorder;
• History of myasthenia gravis;
• Pregnant or breastfeeding woman;
• Unable to understand or respond to questions;
• Contraindication to botulinum toxin or corticoid;
• Treatment with botulinum toxin 3 months prior to baseline;
• Anticoagulant theraphy;
• Difficult to follow-up in the study;
• Patient under guardianship, or deprived of liberty by a judicial order.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Group A : Association (botulinum toxin + corticoid)	Drug: Injection, botulinum toxin + corticoid; Intramuscular injection of botulinum toxin (Xeomin® 50 U) under ultrasound control; Subcutaneous injection (lateral epicondylitis side) of corticoid (2 ml of Hydrocortancyl® 2,5 %)
Placebo Comparator: Group C : placebo of toxin + corticoid :	Drug: Injection, placebo of toxin + corticoid; Intramuscular injection of placebo botulinum toxin (2 ml) under ultrasound control; Subcutaneous injection (lateral epicondylitis side) of corticoid (2 ml of Hydrocortancyl® 2,5 %)
Active Comparator: Group T : botulinum toxin + placebo corticoid	Drug: Injection, botulinum toxin + placebo corticoid; Intramuscular injection of botulinum toxin (Xeomin® 50 U) under ultrasound control; Subcutaneous injection (lateral epicondylitis side) of placebo of corticoid (2 ml of physiological saline solution NaCL 0.9 %)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Variation of pain intensity between injection of treatment and 6 months after injection	Evaluate the variation of muscle pain intensity in wrist extensor contractions between the moment of injection and the end of the 6th month with the Visual Analogue Scale (VAS).	At the moment of injection
Variation of pain intensity between injection of treatment and 6 months after injection	Evaluate the variation of muscle pain intensity in wrist extensor contractions between the moment of injection and the end of the 6th month with the VAS.	6 months after injection

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Spontaneous pain intensity at rest	Evaluate pain intensity at rest with the VAS.	Before injection, 3 months after injection and 6 months after injection
Pain intensity of motion of wrist flexion	Evaluate pain intensity of motion of wrist flexion with the VAS.	Before injection, 3 months after injection and 6 months after injection
Pain intensity at proximal insertion palpation on epicondylitis muscle	Evaluate pain intensity at proximal insertion palpation on epicondylitis muscle. The palpation will be under ultrasound control.	Before injection, 3 months after injection and 6 months after injection
Number of days of sick leave	Number of days of sick leave will be noted and collected	6 months after injection
The percentage of patients returning to professional activity or sportive activity		6 months after injection
Measurement of prehensile grasp capabilities by a force	The force will be measured by Jamar Hydraulic hand dynamometer.	At baseline, 3 months after injection, 6 months after injection
Functional outcome after injection	Outcome will be evaluated by questionnaire Patient Rated Tennis Elbow Evaluation	At baseline, 3 months after injection, 6 months after injection
Anxiety and depression tests	Hospital Anxiety and Depression scale will be used	At baseline, 3 months after injection, 6 months after injection
Frequence and gravity of adverse events	Adverse events will be collected and their severity will be reported.	At baseline, 3 months after injection, 6 months after injection

Collaborators and Investigators

• Sponsor: Assistance Publique - Hôpitaux de Paris
• Investigators: Study Chair: François Genêt, MD, PhD, Service de Médecine Physique et de Réadaptation Hôpital Raymond Poincaré

Study record dates

Study Major Dates

• Study Start (Actual): April 19, 2019
• Primary Completion (Actual): July 7, 2021
• Study Completion (Actual): August 19, 2021

Study Registration Dates

• First Submitted: December 11, 2017
• First Submitted That Met QC Criteria: December 20, 2017
• First Posted (Actual): December 21, 2017

Study Record Updates

• Last Update Posted (Actual): September 21, 2023
• Last Update Submitted That Met QC Criteria: September 19, 2023
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Keywords: Botulinum toxin; Epicondylitis; Corticoid
• Additional Relevant MeSH Terms: Wounds and Injuries; Musculoskeletal Diseases; Muscular Diseases; Tendon Injuries; Tendinopathy; Arm Injuries; Elbow Tendinopathy; Elbow Injuries; Tennis Elbow; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Cholinergic Agents; Membrane Transport Modulators; Acetylcholine Release Inhibitors; Botulinum Toxins
• Other Study ID Numbers: P160926J; 2017-001709-33 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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