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)
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 combin...
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| Format: | Article |
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Public Library of Science
2016
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| Online Access: | https://eprints.nottingham.ac.uk/38028/ |
| _version_ | 1848795582493097984 |
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| author | Sprigg, Nikola O’Connor, Rebecca Woodhouse, Lisa J. Krishnan, Kailash England, Timothy J. Connell, Louise Anne Walker, Marion F. Bath, Philip M.W. |
| author_facet | Sprigg, Nikola O’Connor, Rebecca Woodhouse, Lisa J. Krishnan, Kailash England, Timothy J. Connell, Louise Anne Walker, Marion F. Bath, Philip M.W. |
| author_sort | Sprigg, Nikola |
| building | Nottingham Research Data Repository |
| collection | Online Access |
| description | 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. |
| first_indexed | 2025-11-14T19:34:23Z |
| format | Article |
| id | nottingham-38028 |
| institution | University of Nottingham Malaysia Campus |
| institution_category | Local University |
| last_indexed | 2025-11-14T19:34:23Z |
| publishDate | 2016 |
| publisher | Public Library of Science |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | nottingham-380282020-05-04T18:12:59Z https://eprints.nottingham.ac.uk/38028/ 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 O’Connor, Rebecca Woodhouse, Lisa J. Krishnan, Kailash England, Timothy J. Connell, Louise Anne Walker, Marion F. Bath, Philip M.W. 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. Public Library of Science 2016-09-09 Article PeerReviewed Sprigg, Nikola, O’Connor, Rebecca, Woodhouse, Lisa J., Krishnan, Kailash, England, Timothy J., Connell, Louise Anne, 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 http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0161359 doi:10.1371/journal.pone.0161359 doi:10.1371/journal.pone.0161359 |
| spellingShingle | Sprigg, Nikola O’Connor, Rebecca Woodhouse, Lisa J. Krishnan, Kailash England, Timothy J. Connell, Louise Anne Walker, Marion F. Bath, Philip M.W. 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) |
| title | 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) |
| title_full | 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) |
| title_fullStr | 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) |
| title_full_unstemmed | 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) |
| title_short | 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) |
| title_sort | 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) |
| url | https://eprints.nottingham.ac.uk/38028/ https://eprints.nottingham.ac.uk/38028/ https://eprints.nottingham.ac.uk/38028/ |