Autologous Bone Marrow Stem Cells in Ischemic Stroke.

A Phase I/II Safety and Tolerability Study Following the Autologous Infusion of Immuno-selected CD34+ Subset Bone Marrow Stem Cells Into Patients With Acute Total Anterior Circulation Ischaemic Stroke

The aim of the study is to determine the safety and tolerability of an autologous CD34+ subset bone marrow stem cell infusion into the middle cerebral artery in patients who have suffered acute total or partial anterior circulation syndrome (TACS/PACS).

The proposed trial will involve the recruitment of a total of 10 patients.

The cells will be collected from each subject recruited, via bone marrow sampling. CD34+ stem cells will then be isolated and harvested during a process of immuno-selection in accordance with the principles of Good Manufacturing Practice. The CD34+ cells will then be directly infused into the area of the stroke intra-arterially using the middle cerebral artery.

Initially, the investigator will monitor each patient for a period of 6 months post-stem cell infusion. Thereafter, they will revert to their previous treatment regime in the clinic.

Assessment of adverse events will be by physical examination and measurement of laboratory parameters. Assessment of efficacy will be by physical examination and the measurement of laboratory, CT and MRI parameters.

Inclusion Criteria:

• Symptoms and signs of clinically definite acute stroke
• Time of stroke onset is known and treatment can be started within 7 days of onset
• CT or MRI brain scanning has reliably excluded both intracranial haemorrhage and structural brain lesions which can mimic stroke (e.g. cerebral tumour)
• The stroke is severe and conforming to the TACS phenotype (weakness, homonymous hemianopia and a focal cognitive deficit (e.g. aphasia) or reduction in consciousness) or PACS phenotype (two out of the three TACS criteria)
• An age range of 30-80 years old
• Stroke confined to MCA territory on CT or MRI brain imaging
• NIHSS score >/= 8

Exclusion Criteria:

• Known defect of clotting or platelet function (but patients on anti-platelet agents can enrol)
• Haematological causes of stroke
• Severe co-morbidity
• Hepatic or renal dysfunction
• The patient is female and of childbearing potential (unless it is certain that pregnancy is not possible) or breast feeding
• Hypo- or hyperglycaemia sufficient to account for the neurological symptoms; the patient should be excluded if their blood glucose is < 3.0 or > 20.0mmol/L
• Patient is likely to be unavailable for follow-up e.g. no fixed home address
• Patients with evidence of life threatening infection (e.g. HIV) or life threatening illness (e.g. advanced cancer)
• Patient was already dependent in activities of daily living before the present acute stroke
• Patients who have been included in any other clinical trial within the previous month