Comparative Study of the Mechanism of Action of Dry Needling and Botulinum Toxin Type A as a Treatment for Lower Limb Post-stroke Spasticity: a Proof of Concept Controlled Trial

Stroke Clinical Trial

— STROKEPOC  

Official title:

Comparative Study of the Mechanism of Action of Dry Needling and Botulinum Toxin Type A as a Treatment for Lower Limb Post-stroke Spasticity: a Proof of Concept Controlled Trial

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06296082
• Other study ID #: 49317
• Status: Not yet recruiting
• Phase: Phase 2
• Start date: May 1, 2024
• Est. completion date: June 30, 2027

Study information

• Verified date: February 2024
• Source: Universiteit Antwerpen
• Contact: Wim Saeys, PhD
• Phone: 003232659893
• Email: wim.saeys[@]uantwerpen.be
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Trial design This study is a protocol of a phase II clinical trial which will be conducted in two countries (Belgium and Spain) to compare the effectiveness of DN and BTX A in reducing post-stroke spasticity in the plantar flexor muscles. This study is a prospective randomized, controlled, multiple-baseline design with blinded assessors. The study will be registered in ClinicalTrials.gov and will have a length of 19 weeks

Trial population Inclusion Criteria: 1) aged 18-75 years old, 2) having lower limb post-stroke spasticity in ankle plantar flexors (MAS scores of 1, 1+ and 2); 3) having had a first stroke; 4) having no more than 12 months of evolution since stroke; 5) having no previous Dry Needling (DN) or Botulinum Toxin type A (BTX A) treatment for spasticity; 6) having ankle PROM ≥ 20° (approx.) when the knee is supported in ~30° flexion; 7) being able to walk independently with or without aids.

Exclusion Criteria: 1) medical conditions interfering with data interpretation; 2) any contraindication to receiving BTX A or PS treatment; 3) If taking anti-spasticity medications, participants must be on stable medication for at least 3 months prior to the start of the study and neither the dose nor the medication can be changed during the tria Interventions Participants will be randomly allocated to the group receiving a session of BTX A or to the group receiving Dry Needling once weekly for 12 weeks. Blinded evaluators will assess the effects before, during, after treatment, and at 4-week follow-up.

The trial will have regular monitoring visits by an independent external monitor to ensure compliance with the protocol and Good Clinical Practices. Monitors may review source documents to confirm accurate data on CRD. The investigator and institution will guarantee direct access to source documents for monitors and regulatory authorities.

Description:

Main objective: to understand the effects that BTX A and Dry Needling have on post-stroke spasticity in the lower limbs at the spinal level. Secondary objectives: to assess their safety, feasibility, muscle and functional level effects, quality of life, and cost-effectiveness.

Main trial endpoints:

Spasticity: it will be measured with the Tonic Stretch Reflex Threshold and its velocity sensitivity. It will be assessed weekly during 15 weeks (in week 3, two assessments will be conducted- one before the treatment and one after) and on the 19th week.

Secondary trial endpoints

• Resistance to passive stretching: measured with the Modified Ashworth Scale (MAS) It will be assessed weekly during 15 weeks and on the 19th week (in week 3, two assessments will be conducted- one before the treatment and one after).

• Gait: measured with instrumented gait analysis and the 10 Meter Walk Test (10MWT). It will be assessed on week 1, 2, 9, 15 and 19.

• Functional mobility: measured with the Time Up and Go (TUG). Assessed on week 1, 2, 9, 15 and 19.

• Muscle ultrasound (morphometric and densitometric variables): measured with ultrasound imaging. Assessed every week from 1 to 15 and on the 19 week (in week 3, two assessments will be conducted - one before the treatment and one after).

• Quality of life: measured with the EuroQoL-5D. Assessed on week 1, 15 and 19.

• Cost-effectiveness: measured with a cost-effectiveness analysis. It will be done after every intervention session (from 3 to 15 week and on 19) Apart from these outcomes, estimates for future randomized controlled trial sample size, recruitment, and consent rates will be determined, as well as the safety and feasibility of both treatments.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 90
• Est. completion date: June 30, 2027
• Est. primary completion date: March 31, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 85 Years

Eligibility

Inclusion Criteria:

1. aged 18-85 years old,

2. having lower limb post-stroke spasticity in ankle plantar flexors (MAS scores of 1, 1+ and 2);

3. having had a first stroke;

4. having no more than 12 months of evolution since stroke;

5. having no previous Dry Needling (DN) or Botulinum Toxin type A (BTX A) treatment for spasticity;

6. having ankle PROM = 20° (approx.) when the knee is supported in ~30° flexion;

7. being able to walk independently with or without aids.

Exclusion Criteria:

1. medical conditions interfering with data interpretation;

2. any contraindication to receiving BTX A or PS treatment;

3. If taking anti-spasticity medications, participants must be on stable medication for at least 3 months prior to the start of the study and neither the dose nor the medication can be changed during the trial.

Related Conditions & MeSH terms

• Muscle Spasticity
• Spasticity as Sequela of Stroke
• Stroke

Intervention

Drug:
• Botulinum toxin type A
Intramuscalar approachment with guidance of EMG or Ultrasound. Reconstitute with: 1 vial of 100 BOTOX Units with 1 ml of sterile unpreserved normal saline (which means 10 BOTOX units per 0.1 ml normal saline). The normal saline indicates 0.9% sodium chloride solution for injection. The . Recommended needle: preferred caliber 30 gauge.

Other:
• Dry Needling
The puncture is intramuscular and is performed with a non-beveled needle of 0.3 mm caliber, filiform, solid, similar to those used in acupuncture, which has been shown to produce less damage at the muscle level (Bosque et al., 2022). It does not inject any substance. The same muscles as in BTX A will be stimulated with repeated insertions to try to provoke at least one Local Twitch Response (LTR) at each muscle location. If no LTR is found, the therapist will continue trying to find an LTR in another location. The intervention is performed under ultrasound guidance (Buttefly portable US), although the physiotherapist may provoke an electric stimulation of the Myofascial Trigger Point (MTrP) to confirm the area of the end plate (motor unit), similarly to the EMG procedure that uses motor stimulation to confirm the injection area of the BTX A.

Locations

Country	Name	City	State
n/a

Sponsors (3)

Lead Sponsor	Collaborator
Universiteit Antwerpen	Aragon Institute of Health Sciences, McGill University

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Frequency and Severity of Adverse Events for DN and BTX A	Frequency and Severity of Adverse Events for DN and BTX A during or after the intervention	At the end of the study: After week 19
Other	Sample size	Estimates for Sample Size Calculation and Recruitment and Consent Rates: These will be measured in the two participating countries to identify determining factors.	At the end of the study: After week 19
Other	Sample size and drop out	The dropout rate during treatment and follow-up for each group (PS and BTX A) will be analyzed.	At the end of the study: After week 19
Primary	tonic stretch reflex threshold	TSRT and µ are novel measures of stretch reflex excitability.	Two baseline measurements at Week 1 and Week 2. From Week 3 (therapy intervention starts) till Week 16 weekly assessments. Three weeks after the end of the intervention period, a final assessment will be conducted
Secondary	Passive Resistance	Modified Ashworth Scale: A 6 point scale to measure passive resistance. 0 No increase in muscle tone; Slight increase in muscle tone, manifested by a catch and release or by minimal. resistance at the end of the 1+ Slight increase in muscle tone, manifested by a catch, followed by minimal resistance throughout the remainder (less than half) of the ROM; More marked increase in muscle tone through most of the ROM, but affected part(s) easily moved; Considerable increase in muscle tone, passive movement difficult; Affected part(s) rigid in flexion or extension	Two baseline measurements at Week 1 and Week 2. From Week 3 (therapy intervention starts) till Week 16 weekly assessments. Three weeks after the end of the intervention period, a final assessment will be conducted
Secondary	Ultrasound Imaging: Morphometric Analysis	Assess the pennation angle and muscle thickness Morphometric of the muscle will be performed using ultrasound. Images will be acquired at different time points to analyze muscle changes.	Two baseline measurements at Week 1 and Week 2. From Week 3 (therapy intervention starts) till Week 16 weekly assessments. Three weeks after the end of the intervention period, a final assessment will be conducted
Secondary	Ultrasound Imaging: Eco-textural Analysis of Muscle:	Assess the pennation angle and muscle thickness Eco-textural analysis of the muscle will be performed using ultrasound. Images will be acquired at different time points to analyze muscle changes.; This will be performed using FIJI software and will be divided into four sub-analyses: gray level co-occurrence matrices, gray level run length matrices, local binary pattern analysis, and blob analysis. The relationship between pixel distribution and type of intervention, as well as functional outcomes, will be quantified.	Two baseline measurements at Week 1 and Week 2. From Week 3 (therapy intervention starts) till Week 16 weekly assessments. Three weeks after the end of the intervention period, a final assessment will be conducted
Secondary	Dynamometry	Muscle force (dynamometer (kg)) by microFET device	Two baseline measurements at Week 1 and Week 2. From Week 3 (therapy intervention starts) till Week 16 weekly assessments. Three weeks after the end of the intervention period, a final assessment will be conducted
Secondary	Gait Analysis	Instrumental Gait Analysis: IMU's (Xsens) will be used to provide spatiotemporal and kinematic parameters of gait.	Week 1, Week 2, Week 9, Week 15 and Week 19
Secondary	10 Meter Walk Test (10MWT)	This clinical test will be performed to assess activity-level functionality.	Week 1, Week 2, Week 9, Week 15 and Week 19
Secondary	Timed up and Go Assessment (TUG)	This clinical test will be performed to assess activity-level functionality.	Week 1, Week 2, Week 9, Week 15 and Week 19
Secondary	Quality of Life EuroQoL 5D	The EQ-5D is a standardized instrument that provides a score on five health dimensions (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression). From this, a weighted health index can be derived for an individual or population.	It will be evaluated at baseline(week 1), during the study(week 9), and in the follow-up (week 19). QALYs will be calculated using the area under the curve analysis.
Secondary	EQ visual analogue scale (EQ VAS)	he EQ VAS records the patient's self-rated health on a vertical visual analogue scale where the endpoints are labelled 'The best health you can image' and 'The worst health you can image'. The VAS can be used as a quantitative measure of health outcome that reflects the patient's own judgement.	It will be evaluated at baseline(week 1), during the study(week 9), and in the follow-up (week 19). QALYs will be calculated using the area under the curve analysis.
Secondary	Cost-effectiveness	Direct and indirect costs related to treatment will be evaluated. The ICER (Incremental Cost-Effectiveness Ratio) in €/QALY	This will be calculated at the end of the study (After week 19)
Secondary	Patient Acceptance	Level of Treatment Acceptance by Patients: This will be determined at the end of the study using the "Stanford Expectations of Treatment Scale (SETS)", the SETS assesses positive and negative treatment expectations with 3 items each on 7-point Likert-scales from 0 'not agree at all' to 6 'fully agree'	At the end of the study (week 19)

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