Intra Articular Injection of Botulinum Toxin Versus Corticoids in Gonarthrosis (TOXART)

Analysis of Antalgic Efficacy of an Intra Articular Injection of Botulinum Toxin Versus Corticoids in Gonarthrosis by Perfusion MRI:a Superiority, Randomized, Controlled, Double Blind Study

We believe we can demonstrate a link between the analgesic action of intra-articular injection of botulinum toxin and synovial inflammation by Dynamic Contrast Enhancement (DCE) perfusion Magnetic Resonance Imaging (MRI).

Study Overview

• Status: Unknown
• Conditions: Joint Diseases; Magnetic Resonance Imaging; Knee; Therapeutics
• Intervention / Treatment: Drug: Botulinum Toxin Type A 100U; Drug: Botulinum Toxin Type A 200U; Drug: Triamcinolone Hexacetonide Inj Susp 20 MG/ML

Detailed Description

Knee osteoarthritis is one of the most common causes of joint pain and functional disability in the general population.

Intra-articular infiltrations of corticoids are indicated for painful crisis especially if accompanied of effusion. However, this effect lasts only 2 weeks.

Given the lack of effective long-term medical-infiltrative treatment, we believe that botulinum toxin type A could be used by its direct action on mediators of neuro-gene inflammation at the joint level and its indirect medullary action by retrograde migration.

To date, 2 published randomized controlled trials and one unpublished Phase Ib clinical trial have shown that botulinum toxin injected intraarticularly improves pain and functionality in gonarthrosis.

Dynamic Contrast Enhancement (DCE) Magnetic Resonance Imaging (MRI) demonstrated the correlation between synovial inflammation and pain in gonarthrosis in a cohort of 454 subjects. It has also made it possible, via the monitoring of synovial inflammation, to demonstrate the efficacy of treatments in patients suffering from rheumatoid arthritis in the early phase, juvenile chronic arthritis or osteoarthritis.

DCE MRI perfusion therefore appears here as the technique of choice to follow the evolution of synovial inflammation after botulinum toxin injection in patients with symptomatic gonarthrosis.

• Study Type: Interventional
• Enrollment (Anticipated): 105
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Anne-Sophie Blain; Phone Number: +33 03 20 22 57 32; Email: Blain.Anne-Sophie@ghicl.net

Study Locations

• France
  • Lille, France, 59000
    • Lille Catholic University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years to 75 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Presenting gonarthrosis of degenerative origin, Kellgren/Lawrence Radiological Stage I to III, with a maturity of more than 18 months
• With pain intensity greater than or equal to 50/100 on an VAS
• In case of bilateral gonarthrosis, the VAS of the contralateral knee must be less than or equal to 30/100
• Presenting a failure of conventional per os treatments (non-steroidal anti-inflammatory drugs, analgesics)
• Affiliated with a social security scheme

• For women of childbearing age:

  • effective contraception for the duration of the study

Exclusion Criteria:

• Patient presenting at the time of the inclusion visit: an inflammatory attack, septic or inflammatory arthritis, a generalized infectious episode in progress
• Local or regional local skin lesion
• Need of an arthroplasty within the next 12 months
• Having received corticosteroids or other molecules in intra-articular infiltration in the last 6 months
• History of traumatic knee injury (bone injury in the past 24 months), bone, ligament or meniscal surgery in the past 24 months
• History of disabling peripheral nerve injury
• Severe bleeding disorders, anticoagulant treatment in progress or double antiplatelet aggregation
• BMI > 35 kg/m2
• Coxarthrosis with projected knee pain
• Pregnant or breastfeeding woman
• Patient under guardianship and protection of justice
• Allergy/contraindication to botulinum toxin type A, corticoids
• Usual contraindication to MRI
• Allergy to the contrast product

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Botulinum Toxin Type A 100U; one intra-articular injection in the painful knee 30 days after the inclusion visit	Drug: Botulinum Toxin Type A 100U; one intra-articular injection of 100 U of botulinum toxin type A, diluted in 2 ml of 0.9% SSI; Other Names: Botox 100 UNT Injection
EXPERIMENTAL: Botulinum Toxin Type A 200U; one intra-articular injection in the painful knee 30 days after the inclusion visit	Drug: Botulinum Toxin Type A 200U; one intra-articular injection of 200 U of botulinum toxin type A, diluted in 4 ml of 0.9% SSI; Other Names: Botox 200 UNT Injection
ACTIVE_COMPARATOR: Triamcinolone Hexacetonide 20 MG/ML; one intra-articular injection in the painful knee 30 days after the inclusion visit	Drug: Triamcinolone Hexacetonide Inj Susp 20 MG/ML; one intra-articular injection of 2 ml Triamcinolone Hexacetonide; Other Names: HEXATRIONE

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Assesment of vascularization by dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) according to the % Area Under the Curve (AUC) of perfusion value	one month post-injection

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pain analysis by the visual analogue scale (VAS)	Evolution kinetics of daily pain collected during the first 3 months post-injection allowing to deduce the onset and duration of analgesic efficacy in number of days. The pain VAS is a continuous scale comprised of a horizontal line, usually 10 centimeters (100 mm) in length, anchored by 2 verbal descriptors, one for each symptom extreme: "no pain" (score of 0) and "pain as bad as it could be" (score of 100 [100-mm scale])	during the first 3 months after injection
Joint amplitude measured by goniometry	To measure range of motion of the knee	at 1, 3, 6 month post-injection
Western Ontario McMaster University Osteoarthritis (WOMAC) Index	An arthritic pain scoring system ranging from 0-no pain/disability to 100-most severe pain/disability	at 1, 3, 6 month post-injection
Two minutes walk	This test measure the distance walked in two minutes	at 1, 3, 6 month post-injection
Frequency of consumption of analgesics		at 1, 3, 6 month post-injection
Amount of consumption of analgesics		at 1, 3, 6 month post-injection

Collaborators and Investigators

• Sponsor: Lille Catholic University
• Collaborators: Allergan
• Investigators: Principal Investigator: Hichem Khenioui, MD, GHICL

Study record dates

Study Major Dates

• Study Start (ANTICIPATED): September 1, 2019
• Primary Completion (ANTICIPATED): November 1, 2021
• Study Completion (ANTICIPATED): April 1, 2022

Study Registration Dates

• First Submitted: October 29, 2018
• First Submitted That Met QC Criteria: October 30, 2018
• First Posted (ACTUAL): October 31, 2018

Study Record Updates

• Last Update Posted (ACTUAL): May 21, 2019
• Last Update Submitted That Met QC Criteria: May 20, 2019
• Last Verified: March 1, 2019

More Information

Terms related to this study

• Keywords: knee; Magnetic Resonance Imaging; Botulinum toxin; Arthrosis
• Additional Relevant MeSH Terms: Musculoskeletal Diseases; Rheumatic Diseases; Arthritis; Osteoarthritis; Osteoarthritis, Knee; Joint Diseases; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Cholinergic Agents; Enzyme Inhibitors; Anti-Inflammatory Agents; Immunosuppressive Agents; Immunologic Factors; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Membrane Transport Modulators; Acetylcholine Release Inhibitors; Neuromuscular Agents; Botulinum Toxins; Botulinum Toxins, Type A; abobotulinumtoxinA; Triamcinolone; Triamcinolone Acetonide; Triamcinolone hexacetonide; Triamcinolone diacetate
• Other Study ID Numbers: RC-P0037

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