Granulocyte colony stimulating factor and physiotherapy after stroke: results of a feasibility randomised controlled trial: stem cell trial of recovery enhancement after Stroke-3 (STEMS-3 ISRCTN16714730)

Sprigg, Nikola and O’Connor, Rebecca and Woodhouse, Lisa J. and Krishnan, Kailash and England, Timothy J. and Connell, Louise Anne and Walker, Marion F. and Bath, Philip M.W. (2016) Granulocyte colony stimulating factor and physiotherapy after stroke: results of a feasibility randomised controlled trial: stem cell trial of recovery enhancement after Stroke-3 (STEMS-3 ISRCTN16714730). PLOS ONE, 11 (9). e0161359. ISSN 1932-6203

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Abstract

Background

Granulocyte-colony stimulating factor (G-CSF) mobilises endogenous haematopoietic stem cells and enhances recovery in experimental stroke. Recovery may also be dependent on an enriched environment and physical activity. G-CSF may have the potential to enhance recovery when used in combination with physiotherapy, in patients with disability late after stroke.

Methods

A pilot 2 x 2 factorial randomised (1:1) placebo-controlled trial of G-CSF (double-blind), and/ or a 6 week course of physiotherapy, in 60 participants with disability (mRS >1), at least 3 months after stroke. Primary outcome was feasibility, acceptability and tolerability. Secondary outcomes included death, dependency, motor function and quality of life measured 90 and 365 days after enrolment.

Results

Recruitment to the trial was feasible and acceptable; of 118 screened patients, 92 were eligible and 32 declined to participate. 60 patients were recruited between November 2011 and July 2013. All participants received some allocated treatment. Although 29 out of 30 participants received all 5 G-CSF/placebo injections, only 7 of 30 participants received all 18 therapy sessions. G-CSF was well tolerated but associated with a tendency to more adverse events than placebo (16 vs 10 patients, p = 0.12) and serious adverse events (SAE) (9 vs 3, p = 0.10). On average, patients received 14 (out of 18 planned) therapy sessions, interquartile range [12, 17]. Only a minority (23%) of participants completed all physiotherapy sessions, a large proportion of sessions (114 of 540, 21%) were cancelled due to patient (94, 17%) and therapist factors (20, 4%). No significant differences in functional outcomes were detected in either the G-CSF or physiotherapy group at day 90 or 365.

Conclusions

Delivery of G-CSF is feasible in chronic stroke. However, the study failed to demonstrate feasibility for delivering additional physiotherapy sessions late after stroke therefore a definitive study using this trial design is not supported. Future work should occur earlier after stroke, alongside on-going clinical rehabilitation.

Item Type: Article
Schools/Departments: University of Nottingham, UK > Faculty of Medicine and Health Sciences > School of Medicine > Division of Rehabilitation and Ageing
University of Nottingham, UK > Faculty of Medicine and Health Sciences > School of Medicine > Division of Clinical Neuroscience
University of Nottingham, UK > Faculty of Medicine and Health Sciences > School of Medicine > Division of Medical Sciences and Graduate Entry Medicine
Identification Number: 10.1371/journal.pone.0161359
Depositing User: Eprints, Support
Date Deposited: 28 Oct 2016 11:13
Last Modified: 13 Oct 2017 19:09
URI: http://eprints.nottingham.ac.uk/id/eprint/38028

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