A randomised placebo-controlled pilot trial of granulocyte-colony stimulating factor in mobilising bone marrow stem cells in sub-acute stroke: the 'Stem cell Trial of recovery EnhanceMent after Stroke' (STEMS) pilot study

ISRCTN	ISRCTN16784092
DOI	https://doi.org/10.1186/ISRCTN16784092
Protocol serial number	Version 1.3 28/06/04
Sponsor	University of Nottingham (UK)
Funder	The Stroke Association (UK) (ref: TSA 01/03)

Submission date: 26/08/2005
Registration date: 31/10/2005
Last edited: 20/12/2007

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

Prof Philip Bath
Scientific

University of Nottingham
Clinical Sciences Building
Nottingham City Hospital Campus
Nottingham
NG5 1PB
United Kingdom

Study information

Primary study design	Interventional
Study design	Randomised placebo controlled pilot trial
Secondary study design	Randomised controlled trial
Scientific title
Study acronym	STEMS
Study objectives	Loss of motor function is common after stroke and often leads to significant long-term disability. Stem cells can be mobilised into the circulation using granulocyte-colony stimulating factor (G-CSF), an approach that has been found to be effective in experimental stroke. We aim to perform a pilot randomised placebo-controlled dose-escalation trial of G-CSF (1 x 10^5 - 3 x 10^6 µ/kg given once or once daily for 5 days, in dosing blocks: 1 dose or 5 doses 1 x 10^5 µkg - 3 x 10^6 µ/kg, with level of 5 dose blocks depending on single dose data) in patients with motor weakness following ischaemic stroke, investigating its safety, feasibility of administration, tolerability, and effects on stem cell mobilisation, impairment, disability and dependency. The interaction between G-CSF and routine rehabilitation will be examined. The study will last 24 months with 42 patients recruited over 19 months allowing 3 months follow-up. The results will help inform the design (inclusion criteria, outcomes, size) of further trials including the planning of a large definitive trial assessing the safety and efficacy (motor recovery and functional outcome) of G-CSF.
Ethics approval(s)	Ethics approval received from the Nottingham Local Research Committee on the 5th June 2003 and had Medicines and Healthcare Products Regulatory Agency Clinical Trial Authorisation on the 10th March 2003).
Health condition(s) or problem(s) studied	Stroke (ischaemic)
Intervention	Subcutaneous human recombinant G-CSF (filgrastim from Amgen) versus placebo. G-CSF - 1 x 10^5 - 3 x 10^6 µ/kg given once or once daily for 5 days, in dosing blocks: 1 dose or 5 doses 1 x 10^5 µ/kg - 3 x 10^6 µ/kg, with level of 5 dose blocks depending on single dose data.
Intervention type	Other
Primary outcome measure(s)	1. Circulating CD 34+ (flow cytometry) stem cells - aim greater than 10 x 10^6/l 2. Clinical safety: death, recurrent stroke, deterioration, palpable splenomegaly, at 10 days 3. Laboratory safety: white cell count (WCC, differential), platelet count (PC)
Key secondary outcome measure(s)	Clinical efficacy: 1. Impairment (SSS) 2. Disability (Barthel Index, [BI]) 3. Dependency (mRS) 4. Cognition (Mini Mental State Examination [MMSE]) 5. Depression (Zung) 6. Quality of life (EuroQOL) 7. Disposition (home, institution) Outcomes measurd at 10 and 90 days.
Completion date	01/08/2006

Eligibility

Participant type(s)	Patient
Age group	Adult
Sex	All
Target sample size at registration	42
Key inclusion criteria	1. Clinical stroke (lacunar or cortical) 2. 7 - 30 days post-onset 3. Arm and/or leg weakness (Scandinavian Stroke Scale [SSS], arm and/or leg motor power less than 6)
Key exclusion criteria	1. Pre-morbid dependency, modified Rankin scale (mRS) greater than 3 2. Primary intracerebral haemorrhage 3. Dementia 4. Coma (SSS consciousness less than 4) 5. Malignancy 6. Sickle cell disease 7. Pregnancy
Date of first enrolment	01/08/2003
Date of final enrolment	01/08/2006

Locations

Countries of recruitment

United Kingdom
England

Study participating centre

University of Nottingham

Nottingham
NG5 1PB
United Kingdom

Results and Publications

Individual participant data (IPD) Intention to share	No
IPD sharing plan summary	Not provided at time of registration
IPD sharing plan

Study outputs

Output type	Details	Date created	Date added	Peer reviewed?	Patient-facing?
Results article	Results	01/12/2006		Yes	No