None listed
Conditions
Brief summary
Human amnion epithelial cells (hAECs) therapy attenuated infarct growth even when administered 3 days after the onset of stroke. The mechanisms of action involved modulation of the immune response to minimise further injury in the peri-infarct region. Our recent Phase 1 trial has now shown that amniotic stem cells can be given safely at up to 8 million cells/kg i.v.. We thus now propose a Phase 2 dose escalation trial providing a platform for a Phase 3 trial at a later stage. The design is based on the 1:1:1 randomisation (placebo versus 230 million cells or 460 million cells). Based on our published experimental findings and Phase I dose-escalation human safety trial, we hypothesise that hAECs therapy will reduce stroke disability.
Interventions
amnion stem cell will be given by hospital nurse as set dose of 230 million cells or 460 million cells or placebo in the hospital. Patients will be given 230 millions human amnion epithelial cells (hAECs) by intravenous infusion over 2 hours, previously shown to be safe in preterm babies and acute stroke patients. For patients receiving 460 millions hAECs, the treatment will be given over 2 days. This will be done using a standard infusion pump with an agitator to prevent clumping of cells. Each
amnion stem cell will be given by hospital nurse as set dose of 230 million cells or 460 million cells or placebo in the hospital. Patients will be given 230 millions human amnion epithelial cells (hAECs) by intravenous infusion over 2 hours, previously shown to be safe in preterm babies and acute stroke patients. For patients receiving 460 millions hAECs, the treatment will be given over 2 days. This will be done using a standard infusion pump with an agitator to prevent clumping of cells. Each bag has a volume of 200-250 ml. Prior to infusion, the line is primed with cells so that there is no wastage. The bag is disconnected and the intravenous bung (stopper) is flushed with 10 ml of saline at the end of infusion. Adherence to therapy will be determined by assessing the remnant of the hAEC infusion bag at the end of each treatment
Sponsors
Monash Health
Study design
Allocation
Randomised controlled trial
Intervention model
Parallel
Primary purpose
Treatment
Masking
Blinded (masking used) (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
All
Age
18 Years to 85 Years
Healthy volunteers
No
Inclusion criteria
Patients are eligible if 1) age is between 18-85 years old; 2) they present within 24 hours of stroke onset; 3) have National Institute of Health Stroke Scale/NIHSS (tool used in clinical trials for measuring stroke severity) between 6-20; 4) have ischaemic stroke in the territory of the large vessel 26; 5) have less than a 4 point change in NIHSS after receiving Alteplase or Tenecteplase; 6) have less than an 8 point change in NIHSS after receiving clot retrieval; 7) the patient or person responsible (on behalf of participant) signs a consent form after explanation of the trial.
Exclusion criteria
Patients are excluded if 1) there is evidence of improvement after thrombolysis or thrombectomy; 2) they have autoimmune disease, organ transplant, malignancy, are splenectomised, or have infection at the time of stroke 3) they have neurodegenerative disease such as dementia or Parkinson’s disease; 4) are pregnant; 5) have contra-indications for magnetic resonance (MR) imaging such as a pacemaker; 6) initial infarct (on DWI) volume is less or equal to 5 ml or greater than 100 ml 5, 27; 7) they have mild stroke (NIHSS <6) or very severe stroke (NIHSS >20). This is a common strategy used in many studies to exclude infarcts with very small volume and likely good spontaneous outcome; very large infarcts are excluded as these patients have high probability of developing malignant middle cerebral artery infarction and death. Further exclusion criteria are 8) blood sugar level less or equal to 3 mml/L or equal or greater than 20 mmol/L; 9) significant lung disease requiring oxygen; 10) severe renal impairment.
Outcome results
None listed