Clinical trial NCT03726788: Intra Articular Injection of Botulinum Toxin Versus Corticoids in Gonarthrosis
Official title: 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
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Joint Diseases
Knee
Therapeutics
Magnetic Resonance Imaging
Keywords: knee
Arthrosis
Botulinum toxin
Magnetic Resonance Imaging
Lead sponsor: Lille Catholic University
Sponsor class: OTHER
Collaborators: name: Allergan
First posted: 2018-10-31
Enrollment: 105
Sex: ALL
Minimum age (years): 40
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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To date, 2 published randomized controlled trials and one unpublished Phase Ib clinical trial have shown that botulinum toxin injected intraarticularly improves pain and functionality in gonarthrosis.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

Eligibility criteria: 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

Primary outcomes:
measure: Assesment of vascularization by dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) according to the % Area Under the Curve (AUC) of perfusion value
timeFrame: one month post-injection
Secondary outcomes:
measure: Pain analysis by the visual analogue scale (VAS)
timeFrame: during the first 3 months after injection
measure: Joint amplitude measured by goniometry
timeFrame: at 1, 3, 6 month post-injection
measure: Western Ontario McMaster University Osteoarthritis (WOMAC) Index
timeFrame: at 1, 3, 6 month post-injection
measure: Two minutes walk
timeFrame: at 1, 3, 6 month post-injection
measure: Frequency of consumption of analgesics
timeFrame: at 1, 3, 6 month post-injection
measure: Amount of consumption of analgesics
timeFrame: at 1, 3, 6 month post-injection
Other outcomes:
Locations:
city: Lille
country: France
facility: Lille Catholic University
Study officials:
affiliation: GHICL
name: Hichem Khenioui, MD
role: PRINCIPAL_INVESTIGATOR
References: