Trial Comparing Botulin Toxin Versus Hyaluronic Acid by Intra-articular Injection for the Treatment of Painful Knee Osteoarthritis (GOTOX)

Randomized Controlled Trial Comparing Botulin Toxin Versus Hyaluronic Acid by Intra-articular Injection for the Treatment of Painful Knee Osteoarthritis

In France, osteoarthritis affects about 10 million people and knee osteoarthritis represents 35% of cases. It is thought that more than 2.5 million people older than 65 years have knee osteoarthritis.

Currently, osteoarthritis management is based on three major axes:

1. Non-pharmacological means, such as patient education, loss of weight and physical activity
2. General pharmacological treatments: mainly paracetamol and then schedule II and III painkillers as well as nonsteroidal anti-inflammatory agent.

3. Intra-articular pharmacological treatments:

   1. Intra-articular injections of corticosteroids: they are recommended during hydarthrotic flare-ups
   2. Intra-articular injections of hyaluronic acid (HA) (viscosupplementation) in the absence of intra-articular effusion. However, their efficacy is questioned by most experts in the case of symptomatic knee osteoarthrosis.
4. Sometimes, surgery is the only therapeutic option. However, besides the fact of exposing patients, who are sometimes frail, to several peri- and post-operative complications, the recovery rate (variable according to the prosthesis type and ranging from 5% to 25% at 9 years) in an ageing population justifies waiting as much as possible before surgery. Therefore, it is important to test new therapeutic options for symptomatic osteoarthrosis that will allow postponing the surgical treatment.
5. The use of botulinum toxin (BoNT-A) could thus represents an interesting alternative. BoNT-A is habitually used by intra-muscular injection for its myorelaxant effect in the management of painful reactive periarticular muscle contractures. However, BoNT-A has also antalgic activity independently of the myorelaxant effect. This allows explaining in part the antalgic effect of intra-articular BoNT-A injection. In the literature, six randomized controlled studies (RCS) have compared BoNT-A and intra-articular injections of corticosteroids, hyaluronic acid, or placebo. Only two RCS concerned knee osteoarthritis and compared BoNT-A to corticosteroids and a placebo, respectively, with a significant antalgic effect only in the groups treated with BoNT-A. No study has compared yet the intra-articular injection of BoNT-A to the viscosupplementation by HA in knee osteoarthritis and this is the aim of this trial.

Study Overview

• Status: Active, not recruiting
• Conditions: Painful Unilateral Femorotibial Knee Osteoarthritis of Any Etiology
• Intervention / Treatment: Drug: Botulinum toxin A ( BoNT-A); Device: Hyaluronic acid (HA)

• Study Type: Interventional
• Enrollment (Actual): 50
• Phase: Phase 2

Contacts and Locations

Study Locations

• France
  • Strasbourg, France, 67091
    • Hôpitaux Universitaires de Strasbourg

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Painful, or predominantly unilateral painful, knee osteoarthritis of any etiology
• Knee without clinical signs of intra-articular effusion
• Kellgren score ≥ II on X-ray
• WOMAC pain sub-score ≥ 5 in the month preceding the inclusion visit

Exclusion Criteria:

Clinical:

• Inflammatory arthropathy,infectious, neoplastic within the past year
• Neuromuscular pathology
• Cardiorespiratory pathology or any other severe disease that interferes with the functional capacities
• Any decompensated or unstable chronic pathology
• Glomerular filtration rate (GFR)<15 mL/min/1.73m²) within the past 6 months
• HBA1c in diabetic people > 12% within the past 6 months
• BMI ≥ 35kg/m2
• Infection: joint, general, distant, cutaneous
• Foreign material in the knee to be treated: prosthesis, osteosynthesis material
• Severe coagulation problem: platelets <100000/mm3 within the past 6 months
• Allergy to BoNT-A
• Allergy to HA
• Pregnant or breast-feeding women
• Treatment with aminoglycosides or direct oral anticoagulants
• Treatment with VKA (antihemorrhagic vitamin) if INR (International Normalized Ratio) higher than 3 within the past month
• Change of anti-pain treatment less than 2 weeks before enrolment
• Treatment with III pain killers or corticosteroids because of intense pain that does not respond to schedule I and II pain-killers
• Intra-articular injection of corticosteroids in the previous two months
• Viscosupplementation and/or injection of BoNT-A in the knee to be treated within the past 6 months
• Injection of BoNT-A (except the knee to be treated) within the past 3 months
• Swallowing troubles

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Intra-articular injection of botulinum toxin A	Drug: Botulinum toxin A ( BoNT-A); Intra-articular injection of BoNT-A
Active Comparator: Intra-articular injection of hyaluronic acid	Device: Hyaluronic acid (HA); Intra-articular injection of Hyaluronic acid

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Evaluation of pain measured using the WOMAC pain sub-score	Change from baseline WOMAC pain sub-score at 3 months

Secondary Outcome Measures

Outcome Measure	Time Frame
Evaluation of the antalgic effect of BoNT-A vs hyaluronic acid measured using a verbal rating scale (VRS)	1 week after injection
Evaluation of the patients' functional improvement based on the WOMAC score ("stiffness and function sub-score" and total score)	Before injection, 1 month, 3 months and 6 months following injection
Evaluation of the patients' functional improvement using the Timed Up-and-go Test	Before injection, 1 month, 3 months and 6 months following injection
Evaluation of the quality of life based on the SF-36 score	Before injection, 1 month, 3 months and 6 months following injection
Frequency, seriousness and severity of adverse event reactions	during the 6 months following injection
Changes in pain treatment score (using a correspondence table)	Change from baseline pain treatment score at 6 months
Changes in muscular strenght et muscular trophicity (using dynanometer and measure of knee and thin circumference)	Before injection, 1 month, 3 months and 6 months following injection
Changes in passive and active articular knee amplitude, by goniometry	Before injection, 1 month, 3 months and 6 months following injection

Collaborators and Investigators

• Sponsor: University Hospital, Strasbourg, France

Study record dates

Study Major Dates

• Study Start (Actual): June 9, 2017
• Primary Completion (Anticipated): October 1, 2021
• Study Completion (Anticipated): December 1, 2021

Study Registration Dates

• First Submitted: May 27, 2016
• First Submitted That Met QC Criteria: July 13, 2016
• First Posted (Estimate): July 14, 2016

Study Record Updates

• Last Update Posted (Actual): September 14, 2021
• Last Update Submitted That Met QC Criteria: September 13, 2021
• Last Verified: September 1, 2021

More Information

Terms related to this study

• Keywords: Pain; Knee osteoarthritis; Function; Hyaluronic acid; Intra-articular botulinum toxin
• Additional Relevant MeSH Terms: Neurologic Manifestations; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Arthritis; Osteoarthritis; Osteoarthritis, Knee; Pain; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Cholinergic Agents; Immunologic Factors; Protective Agents; Membrane Transport Modulators; Adjuvants, Immunologic; Acetylcholine Release Inhibitors; Neuromuscular Agents; Viscosupplements; Botulinum Toxins; Botulinum Toxins, Type A; abobotulinumtoxinA; Hyaluronic Acid
• Other Study ID Numbers: 6122

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