Botulinum Toxin vs Dry Needling for Post-Stroke Muscle Spasms

(STROKEPOC Trial)

Recruiting at 2 trial locations

Overseen By Pablo Herrero Gallego, PhD

Age: 18+

Sex: Any

Trial Phase: Phase 2 & 3

Sponsor: Universiteit Antwerpen

Must not be taking: Anti-spasticity medications

Disqualifiers: Pregnancy, Breastfeeding, Medical conditions, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 13

Duration: 12 weeks

90 Participants Needed

Trial Summary

What is the purpose of this trial?

This is a randomized parallel group clinical trial which will be conducted in three countries (Spain, Canada and Belgium) comparing Botulinum Toxin type A (BTX-A) and Dry Needling (DN) effectiveness for post-stroke spasticity in participants who had a first stroke in the previous 12 months and have plantar flexor spasticity. Participants will be randomly allocated to receive either one session of BTX-A or 12 weekly sessions of DN. Blinded evaluators will assess the effects before, during, and after treatment, and at a 4-week follow-up.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot change the dosage of any anti-spasticity medications during the trial or within the 3 months before joining.

What data supports the effectiveness of the drug Botulinum Toxin Type A for treating post-stroke muscle spasms?

Research shows that Botulinum Toxin Type A is effective in reducing muscle stiffness and spasms in patients who have had a stroke, particularly in the upper limbs. Studies have demonstrated its ability to improve muscle control and reduce spasticity, making it a widely used treatment for post-stroke muscle issues. ^{1 2 3 4 5}

Is botulinum toxin safe for treating post-stroke muscle spasms?

Botulinum toxin type A, used for treating post-stroke muscle spasms, generally shows mild adverse events, indicating it is generally safe for humans. Studies have shown that repeated treatments can improve function and muscle tone, with safety data supporting its use in various conditions. ^{3 6 7 8 9}

How does the drug Botulinum Toxin Type A differ from other treatments for post-stroke muscle spasms?

Botulinum Toxin Type A (Botox) is unique because it is a first-line drug that works by blocking nerve signals to muscles, reducing muscle tightness, and is often administered with precision using ultrasound guidance to improve outcomes. In contrast, dry needling is a non-drug treatment that involves inserting needles into muscle trigger points to relieve spasticity without using any medication. ^{2 4 10 11 12}

Research Team

Pablo Herrero Gallego, PhD

Principal Investigator

Universidad de Zaragoza

Eligibility Criteria

This trial is for adults aged 18-85 who've had their first stroke within the last year and are experiencing lower limb muscle spasms. They should not have had previous treatments with Dry Needling or Botulinum Toxin, be able to walk independently, and have a certain range of ankle movement.

Inclusion Criteria

I can walk by myself, with or without help like a cane.

I have mild to moderate muscle stiffness in my ankle after a stroke.

I had my first stroke less than a year ago.

Exclusion Criteria

Pregnant or breastfeeding

Medical conditions interfering with data interpretation

I have no medical reasons preventing me from receiving Botox or Dysport treatments.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either one session of Botulinum Toxin type A or 12 weekly sessions of Dry Needling

12 weeks

12 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

1 visit (in-person)

Outcome Assessment

Assessment of primary and secondary outcomes including TSRT, muscle thickness, and quality of life

19 weeks

Treatment Details

Interventions

• Botulinum Toxin Type A
• Dry Needling

Trial Overview The study compares two treatments for post-stroke spasticity: one group will receive Botulinum Toxin type A in one session, while another will get Dry Needling weekly for 12 weeks. The effectiveness will be assessed by blinded evaluators before, during, after treatment, and at a follow-up.

Participant Groups

Group I: Botulinum Toxin type A Active Control 1 Intervention

The BTX-A group will receive onabotulinumtoxinA (Botox®, Allergan) with mandatory muscles getting 300 units and optional muscles getting up to 100 additional units (maximum dose of 400 units) (14) delivered with a 27-gauge (0.45 mm) beveled needle. Target muscles will be identified by ultrasound imaging or muscle stimulation. Local anesthesia will not be used. Patient positioning will be standardized.

Group II: Dry Needling Active Control 1 Intervention

For Dry Needling group solid, filiform non-beveled 0.30 mm caliber needles will be used. Target muscles will be identified by ultrasound imaging or muscle stimulation. Local anesthesia will not be used. Patient positioning will be standardized.

Botulinum Toxin Type A is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Botox for:

• Temporary improvement in the appearance of moderate to severe glabellar lines associated with corrugator and/or procerus muscle activity
• Temporary improvement in the appearance of moderate to severe facial wrinkles and folds
• Axillary hyperhidrosis
• Blepharospasm
• Strabismus
• Cervical dystonia
• Chronic migraine
• Overactive bladder
• Detrusor overactivity associated with a neurologic condition

Approved in European Union as Botox for:

• Glabellar lines
• Facial wrinkles and folds
• Axillary hyperhidrosis
• Blepharospasm
• Strabismus
• Cervical dystonia
• Chronic migraine
• Overactive bladder
• Detrusor overactivity associated with a neurologic condition
• Spasticity of the upper limb

Approved in Canada as Botox for:

• Temporary improvement in the appearance of moderate to severe glabellar lines associated with corrugator and/or procerus muscle activity
• Temporary improvement in the appearance of moderate to severe facial wrinkles and folds
• Axillary hyperhidrosis
• Blepharospasm
• Strabismus
• Cervical dystonia
• Chronic migraine
• Overactive bladder
• Detrusor overactivity associated with a neurologic condition

Who Is Running the Clinical Trial?

Universiteit Antwerpen

Lead Sponsor

Trials

241

Recruited

333,000+

European Commission

Collaborator

Trials

255

Recruited

3,285,000+

Instituto de Investigación Sanitaria Aragón

Collaborator

Trials

29

Recruited

29,800+

Instituto de Salud Carlos III

Collaborator

Trials

320

Recruited

648,000+

Fonds de la Recherche en Santé du Québec

Collaborator

Trials

84

Recruited

46,700+

Research Foundation Flanders

Collaborator

Trials

89

Recruited

37,700+

McGill University

Collaborator

Trials

421

Recruited

1,017,000+

Aragon Institute of Health Sciences

Collaborator

Trials

12

Recruited

1,100+

Findings from Research

A meta-analysis of 10 randomized controlled trials involving 950 participants found that botulinum toxin type A did not show significant effectiveness compared to placebo for treating upper limb spasticity after a stroke.

However, the analysis indicated that Dysport, a specific formulation of botulinum toxin, demonstrated a significant improvement in spasticity at the elbow compared to placebo, suggesting it may be more effective than other formulations like Botox.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Botulinum Toxin Type A for Upper Limb Spasticity in Poststroke Patients: A Meta-analysis of Randomized Controlled Trials. Jia, S., Liu, Y., Shen, L., et al.[2020]

In a randomized clinical trial involving 30 post-stroke patients, botulinum toxin type A injections guided by ultrasound resulted in significantly better reductions in spasticity and improved finger position at rest compared to manual needle placement.

Both treatment methods showed improvements after one month, but the ultrasound-guided approach led to superior clinical outcomes, suggesting that accurate delivery of the toxin may enhance treatment effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Can botulinum toxin type A injection technique influence the clinical outcome of patients with post-stroke upper limb spasticity? A randomized controlled trial comparing manual needle placement and ultrasound-guided injection techniques. Santamato, A., Micello, MF., Panza, F., et al.[2018]

Two patients with post-stroke upper limb spasticity, who had developed neutralizing antibodies after treatment with onabotulinumtoxinA, showed good therapeutic responses to incobotulinumtoxinA, indicating its potential effectiveness despite the presence of these antibodies.

The study suggests that incobotulinumtoxinA can be a viable treatment option for patients who have previously experienced reduced efficacy from other botulinum toxin preparations due to antibody development.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

IncobotulinumtoxinA for Post-stroke Upper Limb Spasticity in Neutralizing Antibody-positive Patients after Botulinum Toxin Therapy: A Report of Two Cases. Masakado, Y., Dekundy, A., Tateishi, S., et al.[2022]

In a phase I clinical trial involving 30 patients with post-stroke upper limb spasticity, the new botulinum toxin type A (MT10107) demonstrated similar efficacy to the established treatment (onabotulinumtoxinA) in reducing muscle stiffness, as measured by the modified Ashworth scale.

Both MT10107 and onabotulinumtoxinA were found to be safe, with no significant differences in adverse events or other safety measures, indicating that MT10107 is a viable alternative for treating spasticity in stroke patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and efficacy of MT10107 in post-stroke upper limb spasticity treatment: A phase I randomized controlled trial. Lee, J., Chun, MH., Ko, YJ., et al.[2023]

In a study of 68 patients with early arm poststroke spasticity, local injections of botulinum toxin type A (BTA) were effective in reducing motor disorders and preventing severe spasticity when administered at half the recommended dose.

The treatment not only alleviated symptoms but also helped prevent the formation of early contractures and relieved painful shoulder syndrome, indicating its potential for improving recovery in stroke patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[The use of different doses of botulotoxin A in the treatment of early arm poststroke spasticity]. Agafonova, NV., Khasanova, DR.[2016]

In a study involving poststroke spasticity patients, long-term treatment with botulinum toxin type A (BTX-A) over 42 weeks showed significant and sustained improvements in disability and muscle tone, as measured by Disability Assessment and Ashworth scores.

The treatment was generally safe, with adverse events being mostly mild, indicating that repeated BTX-A treatments can effectively enhance function and reduce spasticity without serious side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Repeated dosing of botulinum toxin type A for upper limb spasticity following stroke. Gordon, MF., Brashear, A., Elovic, E., et al.[2019]

In a study involving 187 stroke patients, the new botulinum neurotoxin type A, Botulax, demonstrated comparable efficacy to Botox in reducing upper limb spasticity, as measured by the modified Ashworth scale.

Both Botulax and Botox showed significant improvements in spasticity and related disability measures, with no significant differences in safety profiles between the two treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and efficacy of letibotulinumtoxinA(BOTULAX®) in treatment of post stroke upper limb spasticity: a randomized, double blind, multi-center, phase III clinical trial. Do, KH., Chun, MH., Paik, NJ., et al.[2018]

In a head-to-head comparison of 31 stroke patients, the novel botulinum toxin A2NTX showed superior efficacy in reducing spasticity and improving mobility compared to BOTOX (onabotulinumtoxinA) by day 30, as measured by the modified Ashworth scale and Functional Independence Measure.

A2NTX demonstrated a better safety profile, as it did not negatively affect grip strength in the unaffected hand, unlike BOTOX, which caused a significant decrease in grip strength, indicating less spread of the toxin to unintended areas.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Pilot Study of A2NTX, a Novel Low-Molecular-Weight Neurotoxin Derived from Subtype A2 for Post-Stroke Lower Limb Spasticity: Comparison with OnabotulinumtoxinA. Kaji, R., Miyashiro, A., Sato, N., et al.[2023]

In a review of adverse events (AEs) from botulinum toxin type-A (BoNTA) used for treating focal spasticity in Canada over four years, 285 AEs were reported, with serious events occurring in 53% of cases, highlighting the need for careful monitoring during treatment.

The most common AEs included muscle weakness (19%), oropharyngeal issues (14%), and respiratory problems (14%), indicating that while BoNTA is effective for spasticity, understanding and mitigating these AEs is crucial for improving patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adverse Clinical Effects of Botulinum Toxin Intramuscular Injections for Spasticity. Phadke, CP., Balasubramanian, CK., Holz, A., et al.[2018]

Dry needling (DN) significantly reduced wrist flexor spasticity in stroke patients, as evidenced by a decrease in Modified Modified Ashworth Scale (MMAS) scores from a median of 2 at baseline to 1 immediately after treatment and one hour later.

The study, involving 29 stroke patients, also showed improvements in other measures of muscle function and excitability, indicating that DN may effectively lower muscle stiffness and enhance movement shortly after treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A single group, pretest-posttest clinical trial for the effects of dry needling on wrist flexors spasticity after stroke. Fakhari, Z., Ansari, NN., Naghdi, S., et al.[2018]

A case study of a 62-year-old male with chronic shoulder spasticity post-stroke showed significant improvement in spasticity and shoulder range of motion after 9 sessions of dry needling targeting specific muscle trigger points.

The results suggest that dry needling can be an effective treatment for alleviating chronic post-stroke shoulder spasticity, providing a non-drug intervention option for patients with similar conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dry needling at myofascial trigger points mitigates chronic post-stroke shoulder spasticity. Tang, L., Li, Y., Huang, QM., et al.[2020]

A panel of experts reached consensus on specific treatment paradigms for poststroke spasticity (PSS) in the upper limb, recommending targeted muscle injections of onabotulinumtoxinA with doses ranging from 10 to 100 U per muscle, and total doses per posture between 50 to 400 U.

Localization guidance techniques were deemed essential for effective treatment, and the panel emphasized the importance of adjusting doses or the number of muscles treated if the initial response to onabotulinumtoxinA was suboptimal.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

OnabotulinumtoxinA Injection for Poststroke Upper-Limb Spasticity: Guidance for Early Injectors From a Delphi Panel Process. Simpson, DM., Patel, AT., Alfaro, A., et al.[2018]

References

1. United States pubmed.ncbi.nlm.nih.gov

Botulinum Toxin Type A for Upper Limb Spasticity in Poststroke Patients: A Meta-analysis of Randomized Controlled Trials. [2020]

2. Netherlands pubmed.ncbi.nlm.nih.gov

Can botulinum toxin type A injection technique influence the clinical outcome of patients with post-stroke upper limb spasticity? A randomized controlled trial comparing manual needle placement and ultrasound-guided injection techniques. [2018]

3. Japan pubmed.ncbi.nlm.nih.gov

IncobotulinumtoxinA for Post-stroke Upper Limb Spasticity in Neutralizing Antibody-positive Patients after Botulinum Toxin Therapy: A Report of Two Cases. [2022]

4. United States pubmed.ncbi.nlm.nih.gov

Safety and efficacy of MT10107 in post-stroke upper limb spasticity treatment: A phase I randomized controlled trial. [2023]

5. Russia (Federation) pubmed.ncbi.nlm.nih.gov

[The use of different doses of botulotoxin A in the treatment of early arm poststroke spasticity]. [2016]

6. United States pubmed.ncbi.nlm.nih.gov

Repeated dosing of botulinum toxin type A for upper limb spasticity following stroke. [2019]

7. England pubmed.ncbi.nlm.nih.gov

Safety and efficacy of letibotulinumtoxinA(BOTULAX®) in treatment of post stroke upper limb spasticity: a randomized, double blind, multi-center, phase III clinical trial. [2018]

8. Switzerland pubmed.ncbi.nlm.nih.gov

A Pilot Study of A2NTX, a Novel Low-Molecular-Weight Neurotoxin Derived from Subtype A2 for Post-Stroke Lower Limb Spasticity: Comparison with OnabotulinumtoxinA. [2023]

9. England pubmed.ncbi.nlm.nih.gov

Adverse Clinical Effects of Botulinum Toxin Intramuscular Injections for Spasticity. [2018]

10. Netherlands pubmed.ncbi.nlm.nih.gov

A single group, pretest-posttest clinical trial for the effects of dry needling on wrist flexors spasticity after stroke. [2018]

11. India pubmed.ncbi.nlm.nih.gov

Dry needling at myofascial trigger points mitigates chronic post-stroke shoulder spasticity. [2020]

12. United States pubmed.ncbi.nlm.nih.gov

OnabotulinumtoxinA Injection for Poststroke Upper-Limb Spasticity: Guidance for Early Injectors From a Delphi Panel Process. [2018]