Botulinum Toxin Type A (BT-A) in Hemiplegic Shoulder Pain Versus Steroid

Intra-articular Injection of Botulinum Toxin Type A in Hemiplegic Shoulder Pain: a Multicentric, Double Blind Randomised, Versus Steroid Study

The aim of this study is to confirm the efficacy and safety of the intra-articular injection of BT-A in a multicentric double blind randomised study. For this purpose intra-articular injection of BT-A will be compared with the intra-articular steroid injection that is the current "gold standard" for the treatment of HSP.

Study Overview

• Status: Unknown
• Conditions: Stroke; Shoulder Pain; Hemiparesis
• Intervention / Treatment: Drug: BT-A (Dysport 500U), Triamcinolone acetonide

Detailed Description

Shoulder pain is one of the most common complications of stroke. In fact, it occurs up to 70% of stroke victims. Post-stroke shoulder pain impacts negatively on daily activities. Moreover, it interferes with the rehabilitation process, is related to poor quality of life and has been associated to a worse outcome and to prolonged hospitalization.The aetiology of post-stroke HSP is uncertain, although it has been associated with various factors: joint disorders, capsulitis adhesive, subluxation of the head of the humerus, rotator cuff tendons injuries and spasticity of surrounding muscles. Clinicians use a wide variety of approaches to treat post-stroke HSP, although none has yet been proven effective. Correct positioning and careful handling of the hemiplegic limb are believed to prevent HSP. Physiotherapy alone does not seem to be effective for this complication. Capsulitis adhesive can be successfully treated with corticosteroid injections in the shoulder. However, despite many randomized controlled trials of corticosteroid injections for shoulder pain, their effects remain controversial. The large number of interventions and the lack of consensus about their effectiveness suggest that the aetiology is poorly understood and hence its treatment remains to be established. Intramuscular injections of botulinum toxin type A (BT-A) have also been demonstrated to reduce HSP. The mechanism whereby intramuscular inoculation of BT-A reduces pain may include a muscle relaxant effect and inhibition of the release of neurotransmitters by sensory neurons. Nevertheless, this approach has some limitations: it is probably more effective in muscular than in articular pain and it may be influenced by the muscles affected and site of injection. Intra-articular injection of BT-A has recently proven safe and effective in the treatment of refractory joint shoulder pain caused by chronic arthritis. The mechanisms by which it exerts this effect are not known, but could include inhibition of the release of pain peptides from nerve terminals and sensory ganglia, and anti-inflammatory and anti-glutaminergic effects.

• Study Type: Interventional
• Enrollment (Anticipated): 52
• Phase: Phase 2

Contacts and Locations

Study Locations

• Italy
  • Palermo
    • Cefalù, Palermo, Italy, 90015
      • Fondazione Istituto San Raffaele G. Giglio di Cefalù

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients with hemiparesis and shoulder pain due to first stroke (ischemic or hemorrhagic) admitted in a rehabilitative department to carry out a standard post-acute rehabilitative program
• Pain score of 45 or greater on a 0-100 mm pain visual analog scale (VAS; 0 = no pain, 100 = worst possible pain)
• Duration of HSP for at least one month
• Pain refractoriness to conventional treatment i.e. common analgesics (such as paracetamol and NSAIDs), slings, strapping and handling of the arm, functional electrical stimulation of shoulder muscles

Exclusion Criteria:

• Significant spasticity in the upper shoulder joint, defined as a score of 2 or more at the modified Ashworth scale
• History of shoulder pain or shoulder diseases.
• History of neurological diseases (i.e. Parkinson disease, dystonia).
• History of botulinum toxin treatment

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
Active Comparator: BT-A (Dysport 500U)	Drug: BT-A (Dysport 500U), Triamcinolone acetonide; All patients will be randomize to receive an intra-articular injection of BT-A (Dysport 500U) or triamcinolone acetonide (40 mg). Both drugs will be reconstituted with 2.0 ml of saline. Both drugs will be injected in the glenohumeral joint with a standard posterior approach. The time of the intra-articular injection od BT-A or steroid will be considered the "time zero" for each patient. The primary and secondary efficacy variables will be evaluated in all patients at 1 week, 2 weeks, 4 weeks, 3 months and 6 months after the treatment.
Active Comparator: Triamcinolone acetonide	Drug: BT-A (Dysport 500U), Triamcinolone acetonide; All patients will be randomize to receive an intra-articular injection of BT-A (Dysport 500U) or triamcinolone acetonide (40 mg). Both drugs will be reconstituted with 2.0 ml of saline. Both drugs will be injected in the glenohumeral joint with a standard posterior approach. The time of the intra-articular injection od BT-A or steroid will be considered the "time zero" for each patient. The primary and secondary efficacy variables will be evaluated in all patients at 1 week, 2 weeks, 4 weeks, 3 months and 6 months after the treatment.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Therapeutic superiority of BTA respect steroid in HSP, in patients with hemiparesis and shoulder pain due to stroke (ischemic or hemorrhagic).	The primary efficacy outcome will be the reduction in pain severity, measured by VAS score after 4 weeks of treatment, with respect to baseline evaluation. A difference of about 10 mm between treatments, in the reduction of pain severity, as measured by a VAS scale after 4 weeks, will be considered as clinically significant.	one year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Improvement of upper limb functions and activity	The secondary efficacy outcome will include the following measures: VAS score at the other time points of the study (1 week, 2 weeks, 3 months and 6 months after the treatment), Shoulder Pain and Disability Index (SPADI), Modified Ashworth Scale (MAS), Fugl Meyer Assessment Scale (FMAS), NIH Stroke Scale index (NISS), Functional Independent Measure (FIM), quality of life on short-form (SF)-36 subscales (SF-36).	one year
Improvement of quality of life	The secondary efficacy outcome will include the following measures: VAS score at the other time points of the study (1 week, 2 weeks, 3 months and 6 months after the treatment), Shoulder Pain and Disability Index (SPADI), Modified Ashworth Scale (MAS), Fugl Meyer Assessment Scale (FMAS), NIH Stroke Scale index (NISS), Functional Independent Measure (FIM), quality of life on short-form (SF)-36 subscales (SF-36).	one year
Safety Variables	Safety will be assessed through the collection of adverse events (AEs) and changes in the strength of the deltoid, trapezium, biceps and triceps muscles. All treated patients, no matter the duration of treatment, will be considered for the safety analysis. Adverse events will be fully described and presented in frequency tables whereas changes in the strength of abovementioned muscles will be summarised by descriptive statistics (mean, standard deviation, minimum and maximum), for the two treatment groups.	one year

Collaborators and Investigators

• Sponsor: The Foundation Institute San Raffaele G. Giglio of Cefalù
• Collaborators: Azienda Ospedaliero, Universitaria Pisana; Università degli Studi di Ferrara; IRCCS San Camillo, Venezia, Italy; Fondazione Salvatore Maugeri; Ospedale di Brunico
• Investigators: Study Director: Giuseppe Galardi, Dr, San Raffaele-Giglio Foundation

Study record dates

Study Major Dates

• Study Start: January 1, 2012
• Primary Completion (Anticipated): June 1, 2012
• Study Completion (Anticipated): January 1, 2013

Study Registration Dates

• First Submitted: November 7, 2011
• First Submitted That Met QC Criteria: November 14, 2011
• First Posted (Estimate): November 17, 2011

Study Record Updates

• Last Update Posted (Estimate): November 17, 2011
• Last Update Submitted That Met QC Criteria: November 14, 2011
• Last Verified: November 1, 2011

More Information

Terms related to this study

• Keywords: Steroid; Hemiplegic shoulder pain; Intra-articular injection; Botulinum toxin type A (BT-A); Pain score of 45 or greater on a 0-100 mm VAS; Duration of HSP for at least one month; Pain refractoriness to conventional treatment
• Additional Relevant MeSH Terms: Nervous System Diseases; Pain; Neurologic Manifestations; Joint Diseases; Musculoskeletal Diseases; Arthralgia; Shoulder Pain; Paresis; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; 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; abobotulinumtoxinA; Triamcinolone; Triamcinolone Acetonide; Triamcinolone hexacetonide; Triamcinolone diacetate
• Other Study ID Numbers: 2011-004682-32