StrokePhase 4NCT02505802
The Effectiveness of Early Botulinum Toxin A Injection for Lower Limbs Spasticity in Subacute Stroke Adults
A Phase 4 study testing BoNT-A injection in people with Stroke and Muscle Spasticity, run by Sir Run Run Shaw Hospital at 1 site in China.
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… Read more about this study
- Who is it for?
- Ages 18 to 80 yearsHealthy volunteers can take part
- Conditions the study is for
- Stroke, Muscle Spasticity
- What is being tested?
- BoNT-A injection
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- 1 siteChina
- Study dates
- Jan 2014to Jan 2017
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 80 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Were over the age of 18 and less than 80 years and had a stroke within 6 weeks.
- Had slight spasticity of the triceps surae as defined by a score of 1-1+ on the Modified Ashworth Scale (MAS) or ankle clonus (+).
- Had sufficient cognitive and communication ability as defined by MMSE (mini-mental state examination)>25.
- Couldn't dorsiflex ankle and their LEMI (Lower Extremity Motor Index) < 10.
- Were not receiving concurrent aminoglycoside antibiotics and oral anti-spasticity medication
Who cannot join
- Known allergy or sensitivity to study medication or its components.
- Infection or dermatological condition at the injection sites.
- 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.
- 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
- 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%).
- Concurrent use of aminoglycoside antibiotics or other agents that might interfere with neuromuscular function.
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- Patients with severe cognitive impairment or neurological diseases affecting the implementation or evaluation of the test, and drug-dependent patients.
- Presence of clinically unstable severe cardiovascular, renal or respiratory disease
- Researchers believe there are other factors unfit to participate in this study of patients.
Trial locations and contacts
1 site in 1 country.
China1 site, 1 recruiting
- Recruiting
Sir Run Run Shaw Hospital, Medical College of Zhejiang University
Hangzhou, Zhejiang, 310016
TAO WU, MD, wutao1880@163.com
JIANHUA LI, MD, zjdxsyfkfk@126.com
About this study
Official title: Phase III Study of Botulinum Toxin A Injection for Lower Limbs Spasticity in Subacute Stroke Adults
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.
Read the detailed 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.
- Conditions
- Stroke, Muscle Spasticity
- Being tested
- BoNT-A injection
- Keywords
- Stroke, Botulinum Toxins, Muscle Spasticity, Gait
- Medical subject headings
- Stroke, Muscle Spasticity
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BoNT-A injectionDrug
Also called Botulinum toxin A
In BoNT-A treatment group patients received 200 units BoNT-A injection in the triceps surae (150iu) and tibial muscle posterior (50iu).
| Study group | Role | What they receive |
|---|---|---|
| BoNT-A treatment group | Experimental | In BoNT-A treatment group patients received 200 units BoNT-A injection in the triceps surae (150iu) and tibial muscle posterior (50iu). Both groups received comprehensive rehabilitation for 8 weeks. Receives: Drug: BoNT-A injection |
| Control group | No intervention | No special treatment was performed in the control group. Both groups received comprehensive rehabilitation for 8 weeks. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change from baseline of Calf muscle modified Ashworth scale assess (MAS)
Measured: The outcome will be undertaken at weeks 0 (baseline), 8, 12 and 24 weeks later
Secondary outcomes (4)
Lower limbs Fugl-Meyer (FM) score
Measured: The outcome will be undertaken at weeks 0 (baseline), 8, 12 and 24 weeks later
Average integrated sEMG levels of gastrocnemius
Average integrated surface electromyography (sEMG) levels of gastrocnemius during the slow passive dorsiflexion of the ankle.
Measured: The outcome will be undertaken at weeks 0 (baseline), 8, 12 and 24 weeks later
6-min walking distance
Measured: The outcome will be were assessed 8, 12, 24 weeks after injection.
Gait analysis (step length，cadence，speed).
Measured: The outcome will be undertaken at weeks 0 (baseline), 8, 12 and 24 weeks later
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Jul 2015 (estimated)
- Study startJan 2014
- Primary completionJan 2017 (estimated)
- Study completionJan 2017 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (6)Papers the sponsor has linked to this study.
- Other trials for StrokeStudies of the same condition, open and under way.
- More trials run by Sir Run Run Shaw HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 30 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Sir Run Run Shaw Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, TAO WU, Sir Run Run Shaw Hospital
- Investigators
- TAO WU, MD, Study director, Sir Run Run Shaw Hospital, College of Medicine, Zhejiang University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02505802
- Sponsor's protocol ID
- 2013KYB163
- Status last verified
- Jul 2015
- First submitted
- 17 Jul 2015
- Last updated
- 22 Jul 2015
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Lundstrom E, Terent 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.
PubMed 18355307Sommerfeld 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. doi: 10.1161/01.STR.0000105386.05173.5E. Epub 2003 Dec 18.
PubMed 14684785McIntyre 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 Nov-Dec;19(6):479-90. doi: 10.1310/tsr1906-479.
PubMed 23192713Kaji 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/s00415-010-5526-3. Epub 2010 Apr 1.
PubMed 20358216Cosgrove 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. doi: 10.1111/j.1469-8749.1994.tb11863.x.
PubMed 8168656Santamato 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-label study. Eur J Phys Rehabil Med. 2013 Aug;49(4):483-9. Epub 2013 Mar 13.
PubMed 23480980
Study at a glance
From the registry record, last updated by the sponsor on 22 Jul 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase III Study of Botulinum Toxin A Injection for Lower Limbs Spasticity in Subacute Stroke Adults
- ClinicalTrials.gov ID
- NCT02505802
- Acronym / sponsor ID
- 2013KYB163
- Conditions
- Stroke, Muscle Spasticity
- Keywords
- Stroke, Botulinum Toxins, Muscle Spasticity, Gait
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 30 participants (estimated)
- Lead sponsor
- Sir Run Run Shaw HospitalUniversity, hospital or other
- Study start
- Jan 2014
- Primary completion
- Jan 2017 (estimated)
- Study completion
- Jan 2017 (estimated)
- First posted
- 22 Jul 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed 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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| BoNT-A treatment group | Experimental | Drug: BoNT-A injectionIn BoNT-A treatment group patients received 200 units BoNT-A injection in the triceps surae (150iu) and tibial muscle posterior (50iu). Both groups received comprehensive rehabilitation for 8 weeks. |
| Control group | No intervention | –No special treatment was performed in the control group. Both groups received comprehensive rehabilitation for 8 weeks. |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Were over the age of 18 and less than 80 years and had a stroke within 6 weeks.
- Had slight spasticity of the triceps surae as defined by a score of 1-1+ on the Modified Ashworth Scale (MAS) or ankle clonus (+).
- Had sufficient cognitive and communication ability as defined by MMSE (mini-mental state examination)>25.
- Couldn't dorsiflex ankle and their LEMI (Lower Extremity Motor Index) < 10.
- Were not receiving concurrent aminoglycoside antibiotics and oral anti-spasticity medication
Key exclusion criteria (9 listed)
- Known allergy or sensitivity to study medication or its components.
- Infection or dermatological condition at the injection sites.
- 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.
- 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
- 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%).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| BoNT-A injectionAlso: Botulinum toxin AIn BoNT-A treatment group patients received 200 units BoNT-A injection in the triceps surae (150iu) and tibial muscle posterior (50iu). | Drug | BoNT-A treatment group |
Primary outcome
Change from baseline of Calf muscle modified Ashworth scale assess (MAS)
Time frame: The outcome will be undertaken at weeks 0 (baseline), 8, 12 and 24 weeks later
4 secondary outcomes
Lower limbs Fugl-Meyer (FM) score
Time frame: The outcome will be undertaken at weeks 0 (baseline), 8, 12 and 24 weeks later
Average integrated sEMG levels of gastrocnemius
Time frame: The outcome will be undertaken at weeks 0 (baseline), 8, 12 and 24 weeks later
6-min walking distance
Time frame: The outcome will be were assessed 8, 12, 24 weeks after injection.
Gait analysis (step length，cadence，speed).
Time frame: The outcome will be undertaken at weeks 0 (baseline), 8, 12 and 24 weeks later
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Jul 2015.
- Results publication: PubMed 18355307Lundstrom E, Terent 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.
- Results publication: PubMed 14684785Sommerfeld 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. doi: 10.1161/01.STR.0000105386.05173.5E. Epub 2003 Dec 18.
- Results publication: PubMed 23192713McIntyre 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 Nov-Dec;19(6):479-90. doi: 10.1310/tsr1906-479.
- Results publication: PubMed 20358216Kaji 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/s00415-010-5526-3. Epub 2010 Apr 1.
- Results publication: PubMed 8168656Cosgrove 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. doi: 10.1111/j.1469-8749.1994.tb11863.x.
- Results publication: PubMed 23480980Santamato 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-label study. Eur J Phys Rehabil Med. 2013 Aug;49(4):483-9. Epub 2013 Mar 13.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
TAO WU, MD study director
Sir Run Run Shaw Hospital, College of Medicine, Zhejiang University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing BoNT-A injection in people with Stroke and Muscle Spasticity, run by Sir Run Run Shaw Hospital at 1 site in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 22 Jul 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact TAO WU, MD (86 571 86006054, wutao1880@163.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change from baseline of Calf muscle modified Ashworth scale assess (MAS) (time frame: The outcome will be undertaken at weeks 0 (baseline), 8, 12 and 24 weeks later). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02505802, which also lists 6 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Jul 2015.