The Effectiveness of Early Botulinum Toxin A Injection for Lower Limbs Spasticity in Subacute Stroke Adults

Stroke Clinical Trial

Official title:

Phase III Study of Botulinum Toxin A Injection for Lower Limbs Spasticity in Subacute Stroke Adults

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02505802
• Other study ID #: 2013KYB163
• Status: Recruiting
• Phase: Phase 4
• First received: July 17, 2015
• Last updated: July 20, 2015
• Start date: January 2014
• Est. completion date: January 2017

Study information

• Verified date: July 2015
• Source: Sir Run Run Shaw Hospital
• Contact: TAO WU, MD
• Phone: 86 571 86006054
• Email: wutao1880[@]163.com
• Is FDA regulated: No
• Health authority: China: Health and Family Planning Commission of Zhejiang Province
• Study type: Interventional

Clinical Trial Summary

Botulinum toxin A (BoNT-A) injections are widely used to treat spasticity after stroke. Although this treatment is effective on muscle tone improvement, its effect on gait and ability of daily living on early stage of stroke adults remains uncertain.The purpose of this study is to determine whether an early calf muscle injection of low dose BoNT-A in severely affected patients within 6 weeks after stroke could help to hold back disabling muscle spasticity and improve walking dysfunction.

Description:

The high prevalence of stroke is a global problem causing well-known long-term disabilities. Post-stroke lower-extremity spasticity may cause severe functional limitations and pain. Spasticity is a phenomenon defined as disordered sensory-motor control, resulting from upper motor neuron (UMN) lesion, presenting as intermittent or sustained involuntary activation of muscles . Spasticity may interfere with motor function, and is a common reason for clinical interventions such as by physiotherapy, use of orthoses or other technical devices or drugs. Botulinum toxin A (BoNT-A) is a potent neurotoxin that is produced by the bacterium clostridium botulinum. BoNT-A, by blocking acetylcholine release at neuromuscular junctions, accounts for its therapeutic action to relieve dystonia, spasticity, and related disorders.

Unfortunately, intramuscular injections of botulinum often carried out when the patients have obvious spasticity . It is normally given until the clinical signs of an elevated muscle tone have become established; therefore it is usually given at least three months after stroke , . It will impede the rehabilitation of the patients. Accordingly, the present study asked whether an early calf muscle injection of low dose BoNT-A in severely affected patients within 6 weeks after stroke could help to hold back disabling muscle spasticity and improve walking dysfunction along 24 weeks fellow up trail.

This is a randomized, open-label, controlled trial along 24-weeks trails. Referred sample of adult subacute stroke patients (within 6 weeks since stroke, n=30) with mild spasticity of calf muscle will be included. Patients were randomly allocated to BoNT-A treatment group (15 patients) and control group (15 patients). In BoNT-A treatment group patients received 200 units BoNT-A injection in the triceps surae (150iu) and tibial muscle posterior (50iu). No special treatment was performed in the control group. Both groups received comprehensive rehabilitation for 8 weeks. Lower limbs Fugl-Meyer (FM) score, calf muscle modified Ashworth scale assess (MAS), gastrocnemius surface electromyography (sEMG) evaluation and modified Barthel index (MBI) were assessed before and 8, 12, 24 weeks after treatment. Gait analysis (step length，cadence，speed), 6-min walking distance were assessed 8, 12, 24 weeks after injection.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 30
• Est. completion date: January 2017
• Est. primary completion date: January 2017
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years to 80 Years

Eligibility

Inclusion Criteria:

1. Were over the age of 18 and less than 80 years and had a stroke within 6 weeks.

2. Had slight spasticity of the triceps surae as defined by a score of 1-1+ on the Modified Ashworth Scale (MAS) or ankle clonus (+).

3. Had sufficient cognitive and communication ability as defined by MMSE (mini-mental state examination)>25.

4. Couldn't dorsiflex ankle and their LEMI (Lower Extremity Motor Index) < 10.

5. Were not receiving concurrent aminoglycoside antibiotics and oral anti-spasticity medication

Exclusion Criteria:

1. Known allergy or sensitivity to study medication or its components.

2. Infection or dermatological condition at the injection sites.

3. Any medical condition that may put the subject at increased risk with exposure , including diagnosed myasthenia gravis, Eaton-Lambert syndrome, amyotrophic lateral sclerosis, or any other disorder that might have interfered with neuromuscular function.

4. QTc criteria: QTc = 450 millisecond (msec) or=480msec for subjects with Bundle Branch Block-values based on either single electrocardiogram (ECG) values or triplicate ECG averaged QTc values obtained over a brief recording period

5. Liver function tests: aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =2xULN; alkaline phosphatase and bilirubin >1.5xULN (isolated bilirubin >1.5ULN is acceptable if bilirubin is fractionated and direct bilirubin <35%).

6. Concurrent use of aminoglycoside antibiotics or other agents that might interfere with neuromuscular function.

7. Patients with severe cognitive impairment or neurological diseases affecting the implementation or evaluation of the test, and drug-dependent patients.

8. Presence of clinically unstable severe cardiovascular, renal or respiratory disease

9. Researchers believe there are other factors unfit to participate in this study of patients.

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Single Blind (Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Muscle Spasticity
• Stroke

Intervention

Drug:
• BoNT-A injection
In BoNT-A treatment group patients received 200 units BoNT-A injection in the triceps surae (150iu) and tibial muscle posterior (50iu).

Locations

Country	Name	City	State
China	Sir Run Run Shaw Hospital, Medical College of Zhejiang University	Hang Zhou	Zhejiang

Sponsors (1)

Lead Sponsor	Collaborator
Sir Run Run Shaw Hospital

Country where clinical trial is conducted

China, 

References & Publications (6)

Cosgrove AP, Graham HK. Botulinum toxin A prevents the development of contractures in the hereditary spastic mouse. Dev Med Child Neurol. 1994 May;36(5):379-85. — View Citation

Kaji R, Osako Y, Suyama K, Maeda T, Uechi Y, Iwasaki M; GSK1358820 Spasticity Study Group. Botulinum toxin type A in post-stroke lower limb spasticity: a multicenter, double-blind, placebo-controlled trial. J Neurol. 2010 Aug;257(8):1330-7. doi: 10.1007/s — View Citation

Lundström E, Terént A, Borg J. Prevalence of disabling spasticity 1 year after first-ever stroke. Eur J Neurol. 2008 Jun;15(6):533-9. doi: 10.1111/j.1468-1331.2008.02114.x. Epub 2008 Mar 18. — View Citation

McIntyre A, Lee T, Janzen S, Mays R, Mehta S, Teasell R. Systematic review of the effectiveness of pharmacological interventions in the treatment of spasticity of the hemiparetic lower extremity more than six months post stroke. Top Stroke Rehabil. 2012 N — View Citation

Santamato A, Micello MF, Panza F, Fortunato F, Pilotto A, Giustini A, Testa A, Fiore P, Ranieri M, Spidalieri R. Safety and efficacy of incobotulinum toxin type A (NT 201-Xeomin) for the treatment of post-stroke lower limb spasticity: a prospective open-l — View Citation

Sommerfeld DK, Eek EU, Svensson AK, Holmqvist LW, von Arbin MH. Spasticity after stroke: its occurrence and association with motor impairments and activity limitations. Stroke. 2004 Jan;35(1):134-9. Epub 2003 Dec 18. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change from baseline of Calf muscle modified Ashworth scale assess (MAS)		The outcome will be undertaken at weeks 0 (baseline), 8, 12 and 24 weeks later	No
Secondary	Lower limbs Fugl-Meyer (FM) score		The outcome will be undertaken at weeks 0 (baseline), 8, 12 and 24 weeks later	No
Secondary	Average integrated sEMG levels of gastrocnemius	Average integrated surface electromyography (sEMG) levels of gastrocnemius during the slow passive dorsiflexion of the ankle.	The outcome will be undertaken at weeks 0 (baseline), 8, 12 and 24 weeks later	No
Secondary	6-min walking distance		The outcome will be were assessed 8, 12, 24 weeks after injection.	No
Secondary	Gait analysis (step length,cadence,speed).		The outcome will be undertaken at weeks 0 (baseline), 8, 12 and 24 weeks later	No