Efficacy of an Intra-articular Injection of Botulinum Toxin A Associated With Splinting for Base-of-thumb Osteoarthritis (RHIBOT)

Short-term Efficacy of a Single Ultrasound-guided Intra-articular Injection of Botulinum Toxin A Associated With Splinting for Base-of-thumb Osteoarthritis: a Randomized Controlled Double-blind Pilot Study

The primary purpose of this study is to determine whether a single ultrasound-guided intra-articular injection of botulinum toxin A associated to splinting is effective in reducing pain at 3 months in base-of-thumb osteoarthritis.

Study Overview

• Status: Completed
• Conditions: Base-of-thumb Osteoarthritis
• Intervention / Treatment: Drug: botulinum toxin A; Drug: saline

Detailed Description

Base-of-thumb osteoarthritis is a common condition affecting middle-age persons. Base-of-thumb osteoarthritis induces pain and hand-specific limitations in activities. For short and midterm effects, therapeutic options usually include splinting, exercise therapy and intra-articular injections of glucocorticoids or hyaluronic acid. However, evidence of efficacy of intra-articular therapies in base-of-thumb osteoarthritis and international guidelines are inconsistent. Recently, the use of intra-articular botulinum toxin A as a pain killer has raised intense interest. The exact mechanisms of pain modulation by botulinum toxin A in osteoarthritis are unclear. It has been suggested that botulinum toxin A could directly reduce peripheral sensitization and indirectly reduce central sensitization. Indeed, recent studies suggest an inhibitory role of botulinum toxin A on the release of mediators involved in nociception, such as P substance, calcitonin gene-related peptide and glutamate. Open and randomized controlled trials of botulinum toxin A in knee osteoarthritis support short to mid-term positive clinical effects on pain. However, no study has reported results for base-of-thumb osteoarthritis

• Study Type: Interventional
• Enrollment (Actual): 60
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• France
  • Paris, France, 75014
    • Assistance Publique - Hôpitaux de Paris, Service de Rééducation et de Réadaptation de l'Appareil Locomoteur et des Pathologies du Rachis, Hôpital Cochin

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:

• Age ≥ 18 years old
• Pain intensity on a self-administered 11-point pain numeric rating scale ≥ 30
• Pain involving the base-of-thumb
• X-ray evidence of base-of-thumb osteoarthritis with at least 2 of the 4 following items involving the trapeziometacarpal joint : osteophytes, joint space narrowing, subchondral bone sclerosis or subchondral cysts
• 1990 American College of Rheumatology classification criteria for hand osteoarthritis adapted to base-of-thumb osteoarthritis
• Medical examination
• Written consent
• Health insurance
• For women of childbearing age, a negative urinary pregnancy test

Exclusion Criteria:

• History of thumb surgery
• History of inflammatory or crystal-associated rheumatic disease
• Neurological disorders involving the hands other than carpien canal syndrom
• Collagen disorders involving the hands : Dupuytren, Marfan or Ehlers-Danlos diseases
• Osteoarthritis predominating at the scaphotrapezial joint on X-Ray
• Hand or wrist trauma ≤ 2 months
• Hand or wrist intra-articular injections ≤ 2 months
• Contra-indication to botulinum toxin A injection or to splinting
• Cognitive or behavioral disorders making the assessment impossible
• Participant unable to speak, read and write french
• Bilateral BTOA without predominant symptomatic side
• Pregnancy and breast feeding
• Persons referred to in Articles L 1121-5; 6; 8; 9 of the Public Health Code (protected minors or adults, guardianship or trusteeship, etc.)
• Patient with epilepsy

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Intra-articular botulinum toxin A and splinting; Ultrasound-guided injection of 50 Allergan Unities of botulinum toxin A (Botox®, Allergan) resuspended in 1 ml of saline in the trapeziometacarpal joint and custom-made thermoformed plastic splint to be worn for 48 hours after intra-articular injection then nightly	Drug: botulinum toxin A; Ultrasound-guided injection of 50 Allergan Unities of botulinum toxin A (Botox®, Allergan) resuspended in 1 ml of saline in the trapeziometacarpal joint and custom-made thermoformed plastic splint to be worn for 48 hours after intra-articular injection then nightly; Other Names: Allergan; Botox®
Active Comparator: Intra-articular saline and splinting; Ultrasound-guided injection of 1 ml of saline in the trapeziometacarpal joint and custom-made thermoformed plastic splint to be worn for 48 hours after intra-articular injection then nightly	Drug: saline; Ultrasound-guided injection of 1 ml of saline in the trapeziometacarpal joint and custom-made thermoformed plastic splint to be worn for 48 hours after intra-articular injection then nightly

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in base-of-thumb pain 3 months post-injection	Mean change from baseline in average base-of-thumb pain intensity in the previous 48 hrs on a self-administered 11-point pain numeric rating scale (0 no pain - 100 maximal pain)	3 months post injection

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in base-of-thumb pain 1 month post-injection	Mean change from baseline in average base-of-thumb pain intensity in the previous 48 hrs on a self-administered 11-point pain numeric rating scale (0 no pain - 100 maximal pain)	1 month post injection
Change in base-of-thumb pain 6 months post-injection	Mean change from baseline in average base-of-thumb pain intensity in the previous 48 hrs on a self-administered 11-point pain numeric rating scale (0 no pain - 100 maximal pain)	6 months post injection
Change in hand function 3 months post-injection	Mean change from baseline in average hand-specific limitations in activities in the previous 2 weeks on the self-administered Cochin Hand Function Scale (0 no limitations - 90 maximal limitations)	3 months post injection
Change in hand function 6 months post-injection	Mean change from baseline in average hand-specific limitations in activities in the previous 2 weeks on the self-administered Cochin Hand Function Scale (0 no limitations - 90 maximal limitations)	6 months post injection
Change in patient's global assessment 3 months post-injection	Mean change from baseline in patient's global assessment on a self-administered 11-point numeric rating scale (0 worst possible - 100 best possible)	3 months post-injection
Change in patient's global assessment 6 months post-injection	Mean change from baseline in patient's global assessment on a self-administered 11-point numeric rating scale (0 worst possible - 100 best possible)	6 months post-injection
Percentage of OARSI responders 3 months post-injection	OARSI response is defined as an improvement in pain (0 to 100 numeric rating scale) or in function (0 to 90 Cochin Hand Function Scale) ≥ 50% and absolute change ≥ 20/100 on pain numeric rating scale or ≥ 9/90 on Cochin Hand Function Scale respectively , or improvement in at least 2 of the 3 following items: 1/ pain ≥ 20% and absolute change ≥ 10/100, 2/ function ≥ 20% and absolute change ≥ 9/90, 3/ patient's global assessment (0 to 100 numeric rating scale) ≥ 20% and absolute change ≥ 10/100	3 months post-injection
Percentage of OARSI responders 6 months post-injection	OARSI response is defined as an improvement in pain (0 to 100 numeric rating scale) or in function (0 to 90 Cochin Hand Function Scale) ≥ 50% and absolute change ≥ 20/100 on pain numeric rating scale or ≥ 9/90 on Cochin Hand Function Scale respectively , or improvement in at least 2 of the 3 following items: 1/ pain ≥ 20% and absolute change ≥ 10/100, 2/ function ≥ 20% and absolute change ≥ 9/90, 3/ patient's global assessment (0 to 100 numeric rating scale) ≥ 20% and absolute change ≥ 10/100	6 months post-injection
Analgesics consumption at 3 months	Self-reported consumption of analgesics (non-opioid, weak and strong opioids) using a self-administered 4-class scale (never; several times a month; several times a week; daily)	from injection to 3 months post-injection
Analgesics consumption at 6 months	Self-reported consumption of analgesics (non-opioid, weak and strong opioids) using a self-administered 4-class scale (never; several times a month; several times a week; daily)	from 3 to 6 months post-injection
Non-steroidal anti-inflammatory drugs consumption at 3 months	Self-reported consumption of non-steroidal anti-inflammatory drugs using a self-administered 4-class scale (never; several times a month; several times a week; daily)	from injection to 3 months post-injection
Non-steroidal anti-inflammatory drugs consumption at 6 months	Self-reported consumption of non-steroidal anti-inflammatory drugs using a self-administered 4-class scale (never; several times a month; several times a week; daily)	from 3 to 6 months post-injection

Collaborators and Investigators

• Sponsor: Assistance Publique - Hôpitaux de Paris
• Collaborators: Recherche Clinique Paris Descartes Necker Cochin Sainte Anne
• Investigators: Study Director: François RANNOU, MD, PhD, AP-HP , université Paris Descartes; Principal Investigator: Christelle NGUYEN, MD, PhD, AP-HP, université Paris Descartes

Publications and helpful links

General Publications

• Gil C, Abdoul H, Campagna R, Guerini H, Ieong E, Chagny F, Bedin C, Roren A, Lefevre-Colau MM, Poiraudeau S, Feydy A, Rannou F, Nguyen C. Intra-articular botulinum toxin A for base-of-thumb osteoarthritis: protocol for a randomised trial (RHIBOT). BMJ Open. 2018 Jun 30;8(6):e022337. doi: 10.1136/bmjopen-2018-022337.

Study record dates

Study Major Dates

• Study Start (Actual): November 29, 2018
• Primary Completion (Actual): February 16, 2021
• Study Completion (Actual): April 23, 2021

Study Registration Dates

• First Submitted: June 13, 2017
• First Submitted That Met QC Criteria: June 13, 2017
• First Posted (Actual): June 15, 2017

Study Record Updates

• Last Update Posted (Actual): June 30, 2021
• Last Update Submitted That Met QC Criteria: June 26, 2021
• Last Verified: June 1, 2021

More Information

Terms related to this study

• Keywords: Botulinum toxin A; Randomized trial; Base-of-thumb osteoarthritis; Intra-articular therapy
• Additional Relevant MeSH Terms: Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Arthritis; Osteoarthritis; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Cholinergic Agents; Membrane Transport Modulators; Acetylcholine Release Inhibitors; Neuromuscular Agents; Botulinum Toxins; Botulinum Toxins, Type A; abobotulinumtoxinA
• Other Study ID Numbers: P160404

Drug and device information, study documents

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