Condition category
Circulatory System
Date applied
21/10/2011
Date assigned
21/10/2011
Last edited
10/01/2014
Prospective/Retrospective
Retrospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Plain English Summary

Not provided at time of registration

Trial website

Contact information

Type

Scientific

Primary contact

Mr Cameron Lindsay

ORCID ID

Contact details

Keele
Newcastle
ST5 5BG
United Kingdom
camlin3@hotmail.com

Additional identifiers

EudraCT number

2010-021257-39

ClinicalTrials.gov number

NCT01882556

Protocol/serial number

10961

Study information

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

Acronym

EUBoSS

Study hypothesis

EUBoSS- Early Use of Botulinum toxin in post Stroke Spasticity

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

North West 6 REC First MREC approval date 21/04/2011, ref: 10/H1003/111

Study design

Randomised interventional; Design type: Treatment

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Hospitals

Trial type

Treatment

Patient information sheet

Not available in web format, please use the contact details below to request a patient information sheet

Condition

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 names

Botulinum toxin - type A

Primary outcome measures

Action Research Arm Test; Timepoint(s): Baseline, 3 months and 6 months

Secondary outcome measures

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 treatment’s as a consequence of injections

Overall trial start date

03/10/2011

Overall trial end date

31/12/2014

Reason abandoned

Eligibility

Participant 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

Participant type

Patient

Age group

Adult

Gender

Both

Target number of participants

Planned Sample Size: 150; UK Sample Size: 150

Participant 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

Recruitment start date

03/10/2011

Recruitment end date

31/12/2014

Locations

Countries of recruitment

United Kingdom

Trial participating centre

Keele
Newcastle
ST5 5BG
United Kingdom

Sponsor information

Organisation

Keele University (UK)

Sponsor details

Keele
Newcastle
ST5 5BG
United Kingdom

Sponsor type

University/education

Website

Funders

Funder type

Government

Funder name

National Institure for Health Research (NIHR) - Research for Patient Benefit (RfPB) (UK)

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Results and Publications

Publication and dissemination plan

Not provided at time of registration

Intention to publish date

Participant level data

Not provided at time of registration

Results - basic reporting

Publication summary

2014 protocol in: http://www.ncbi.nlm.nih.gov/pubmed/24401159

Publication citations

  1. Protocol

    Lindsay C, Simpson J, Ispoglou S, Sturman SG, Pandyan AD, The early use of botulinum toxin in post-stroke spasticity: study protocol for a randomised controlled trial., Trials, 2014, 15, 12, doi: 10.1186/1745-6215-15-12.

Additional files

Editorial Notes