Intra Articular Injection of Botulinum Toxin Versus Corticoids in Gonarthrosis

Phase 2

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

• Registration Number: NCT03726788
• Lead Sponsor: Lille Catholic University

Brief Summary

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).

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To date, 2 published randomized controlled trials and one unpublished Phase Ib clinical trial have shown that botulinum toxin injected intraarticularly improves pain and functionality in gonarthrosis.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

• Study First Submitted: 2018-10-29
• Study First Submitted QC: 2018-10-30
• Study First Posted: 2018-10-31
• Status Verified: 2019-03
• Last Update Submitted: 2019-05-20
• Last Update Posted: 2019-05-21
• Study Start: 2019-09
• Primary Completion: 2021-11
• Study Completion: 2022-04

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 105

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Botulinum Toxin Type A 100U	Botulinum Toxin Type A 100U	one intra-articular injection in the painful knee 30 days after the inclusion visit
Botulinum Toxin Type A 200U	Botulinum Toxin Type A 200U	one intra-articular injection in the painful knee 30 days after the inclusion visit
Triamcinolone Hexacetonide 20 MG/ML	Triamcinolone Hexacetonide Inj Susp 20 MG/ML	one intra-articular injection in the painful knee 30 days after the inclusion visit

Primary Outcome Measures

Name	Time	Method
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

Name	Time	Method
Amount of consumption of analgesics	at 1, 3, 6 month post-injection
Joint amplitude measured by goniometry	at 1, 3, 6 month post-injection	To measure range of motion of the knee
Western Ontario McMaster University Osteoarthritis (WOMAC) Index	at 1, 3, 6 month post-injection	An arthritic pain scoring system ranging from 0-no pain/disability to 100-most severe pain/disability
Two minutes walk	at 1, 3, 6 month post-injection	This test measure the distance walked in two minutes
Frequency of consumption of analgesics	at 1, 3, 6 month post-injection
Pain analysis by the visual analogue scale (VAS)	during the first 3 months after injection	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 \[100-mm scale\])

Trial Locations

Locations (1)

Lille Catholic University; 🇫🇷 Lille, France