Is it clinically effective to treat arm flexor spasticity, with Botulinum toxin - type A (BoNTA) and physiotherapy, as soon as signs of abnormal muscle activity are observed?

ISRCTN	ISRCTN57435427
DOI	https://doi.org/10.1186/ISRCTN57435427
ClinicalTrials.gov (NCT)	NCT01882556
Clinical Trials Information System (CTIS)	2010-021257-39
Protocol serial number	10961
Sponsor	Keele University (UK)
Funder	Research for Patient Benefit Programme

Submission date: 21/10/2011
Registration date: 21/10/2011
Last edited: 12/06/2019

Recruitment status: No longer recruiting
Overall study status: Completed
Condition category: Circulatory System

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Plain English summary of protocol

Not provided at time of registration

Contact information

Mr Cameron Lindsay
Scientific

Keele
Newcastle
ST5 5BG
United Kingdom

Email	camlin3@hotmail.com

Study information

Primary study design	Interventional
Study design	Randomised interventional; Design type: Treatment
Secondary study design	Randomised controlled trial
Study type	Participant information sheet
Scientific title	Is it clinically effective to treat arm flexor spasticity, with Botulinum toxin type A (BoNTA) and physiotherapy, as soon as signs of abnormal muscle activity are observed: a randomised trial
Study acronym	EUBoSS (Early Use of Botulinum toxin in post Stroke Spasticity)
Study objectives	Patients who survive a stroke are often left with an arm that cannot be used. One reason for this is that the muscles affected by the stroke become overactive. This is known as spasticity. Such unwanted muscle overactivity, if left untreated or poorly managed, can lead to limb deformities. For example, the wrist and fingers in the arm affected by spasticity become stiff and curl into a fist and the hand cannot be used for any functional purpose. Palm hygiene can become difficult and patients find this deformity unsightly and painful. Botulinum toxin (BT) has been shown to reduce muscle overactivity and is licensed for this purpose. In current practice this treatment is often used as a last line of defence. Although BT can reduce the muscle overactivity, when injected using current protocols, it seems to have little impact on the recovery of function and/or treating the limb deformities and pain. If BT can be given in the early stages of a stroke, i.e. as soon as the muscle overactivity is observed, then we will be able to treat spasticity and may prevent the limb deformities and pain from developing. We may also be able to assist the recovery of arm movement in some of the patients who would otherwise not have regained this. In addition to benefiting the patient, the prevention of secondary complications by early treatment may reduce the costs of long term care to the NHS . We hope to discover if our plan of providing early treatment with BT is more effective than the current approach. If we demonstrate that the treatment is effective we will be able to introduce this new method almost immediately within the NHS through our collaboration with doctors and therapists who are actively treating patients with this condition.
Ethics approval(s)	North West 6 REC First MREC approval date 21/04/2011, ref: 10/H1003/111
Health condition(s) or problem(s) studied	Topic: Stroke Research Network; Subtopic: Rehabilitation; Disease: Drug type
Intervention	Patients will receive up to 200 Units of Botulinum Toxin (Botox) to 6 muscles of the upper limb. Placebo group - Patients will receive 0.9% NaCl solution in to 6 muscles of the upper limb. Follow Up Length: 6 month(s)
Intervention type	Drug
Phase	Phase II
Drug / device / biological / vaccine name(s)	Botulinum toxin - type A
Primary outcome measure(s)	Action Research Arm Test; Timepoint(s): Baseline, 3 months and 6 months
Key secondary outcome measure(s)	1. In reducing focal spasticity in the arm as measured by surface electromyography (EMG) response of the wrist and elbow flexors to an externally imposed perturbation 2. In improving strength and fatigue as measured by maximum isometric strength and the rate of force production in the wrist and elbow joints 3. In reducing stiffness and increasing passive range of movement by measuring the range of movement and force required to produce the same with a custom built device 4. In preventing atrophy by measuring cross sectional thickness of biceps muscle as measured using 2D ultrasound - 12MHz probe 5. In reducing post stroke pain measured using a Scale of Pain Intensity (SPIN) 6. In improving quality of life (using the EuroQol Group EQ5D) and assessing carer giver burden (using the Care Giver Burden Scale) 7. In reducing the need for additional oral anti-spasmodic drugs or additional botulinum treatment during the course of rehabilitation 8. In reducing long term costs (quantified using resource utilisation diaries) and identifying discharge destination. 9. Occurrence of adverse events (AEs) during the study 10. In identifying changes in Therapeutic treatments as a consequence of injections
Completion date	31/12/2014

Eligibility

Participant type(s)	Patient
Age group	Adult
Lower age limit	18 Years
Sex	All
Target sample size at registration	150
Key inclusion criteria	1. Over 18 years of age 2. Patients with stroke due to a primary cerebral haemorrhage/infarction, subarachnoid haemorrhage producing an upper motor syndrome affecting one body side which results in a hemiplegia 3. Capable of providing informed consent directly or indirectly, or, consent obtainable from next of kin or legal representative 4. No useful arm function (i.e. less than or equal to 2 on the grasp subsection of the Action Research Arm Test) at onset of spasticity.; Target Gender: Male & Female ; Lower Age Limit 18 years
Key exclusion criteria	1. Significant musculoskeletal conditions that affected upper limb function prior to the stroke 2. Unconscious or moribund during the screening perid 3. Recovery of useful arm function (a score of 3 or more in the grasp section of the Action Research Arm Test) prior to injections 4. Patients with contraindications to electrical stimulation including active implants (e.g. cardiac assist devices), metal implants at site of stimulation, scar tissue/cancerous tissue at site of stimulation, uncontrolled epilepsy, deep vein thrombosis in limb / muscle being stimulated and pregnancy (or planned pregnancy) 5. Previousupper motor neurone syndrome or hypertonicity due to multiple sclerosis, spinal cord injury or other neurological disorder 6. Patients with a known hypersensitivity to any botulinum toxin or to any of the excipients of BOTOX® (i.e. Human serum albumin) 7. Patients with myasthenia gravis or Eaton Lambert Syndrome or other neuromuscular junction or myopathic disorder 8. Patients with infection at the proposed injection site(s) 9. Patients who are pregnant or may become pregnant at the time of the proposed injections and for the duration of the study 10. Current treatment with any antispasticity agent or previous injection with BOTOX
Date of first enrolment	03/10/2011
Date of final enrolment	31/12/2014

Locations

Countries of recruitment

United Kingdom
England

Study participating centre

Keele University

Newcastle
ST5 5BG
United Kingdom

Results and Publications

Individual participant data (IPD) Intention to share	No
IPD sharing plan summary
IPD sharing plan

Study outputs

Output type	Details	Date created	Date added	Peer reviewed?	Patient-facing?
Protocol article	protocol	08/01/2014		Yes	No
Basic results				No	No
HRA research summary			28/06/2023	No	No
Participant information sheet	Participant information sheet	11/11/2025	11/11/2025	No	Yes

Editorial Notes

12/06/2019: Added EudraCT link to basic results (scientific).
03/10/2018: No publications found, verifying study status with principal investigator.