Clinical trial NCT01501773: Intravenous Autologous Bone Marrow-derived Stem Cells Therapy for Patients With Acute Ischemic Stroke
Official title: Phase II Intravenous Autologous Bone Marrow-derived Stem Cells Therapy for Patients With Acute Ischemic Stroke
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Acute Stroke
Keywords: Acute ischemic stroke
Lead sponsor: Manipal Acunova Ltd.
Sponsor class: NETWORK
Collaborators: name: Ministry of Science and Technology, India
First posted: 2011-12-29
Enrollment: 120
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: A multi-centric initiative to study safety,feasibility and efficacy of using intravenous autologous bone marrow mononuclear cells(BMMC) in patients with acute ischemic stroke.This phase of study is visualised as phase 2 study and will aim to determine dose response gradient of stem cell therapy and to explore if there is favorable risk to benefit ratio for autologous stem cell therapy in patient with acute ischamic stroke.

Detailed description: This phase of the study will have two arms developed through random allocation: one arm for intravenous autologous bone marrow derived stem cell/mononuclear cells(BMMC arm); and second control arm. Patients with acute ischaemic stroke between 7-30 days after onset with moderae severity in sable condition will be entered into the study after informed consent. Both arms will receive standard treatment but BMMC arm will,in addition,have bone marrow aspiration and receive autologous 30-500 million bone marrow mononuclear cells intravenously on the day of randomisation and all patients will be followed at DaY 7 ± days, Day 90(-7 days to +14 days), Day 180(-7 days to +28 days)and Day 365 (-7 days to + 28 days). A number of safety and efficacy variables will be measured. This phase 2 study will aim to determine dose response gradient of stem cell therapy and to explore if results have a favourable risk to benefit ratio to justify a phase 3 study. This will be the first human trial to determine and compare favourable and unfavourable effects of bone marrow mononuclear cells(mainly CD34) in acute ischamic stroke and also the first multi-centric study with potential to achieve a reasonable sample size in a relatively short time.

Eligibility criteria: Inclusion Criteria:

1. Sudden onset of focal neurologic deficit or impairment of consciousness.
2. CT or MRI scan of head showing no haematoma and relevant lesions within the MCA and ACA territory.
3. Age between 30 -70 years (after amendment 18 -70 years).
4. \>7 to \</=30 days passed since the onset of the qualifying event.
5. Glasgow Coma Scale score of \>8 at the time of randomization, in aphasic Eye and Motor score of \>6.
6. Modified Barthel Index score of 50 or less at the time of randomization.
7. NHISS score of 7 or more points and inability to walk unaided or raise upper limb by 90 degree.
8. Patient is stable. ( normal respiration, afebrile, BP less than mean arterial pressure of 125 mm of Hg, fasting blood sugar \< 200 mg% and normal urea/electrolytes for at least 48 hours.)

Exclusion Criteria: -

1. Lacunar syndrome
2. Intubation
3. Posterior circulation stroke
4. Co morbidity likely to limit survival to less than 3 years eg. Hepatic or renal failure.
5. Inaccessibility for follow up.
6. Allergy to local anaesthetic.
7. Unwillingness to provide written informed consent.
8. Symptom of acute myocardial infarction or acute involvement of any other organ.
9. Pregnancy 10. HIV positive 11. Patient is a part of any other trial in last 6 months.

Primary outcomes:
measure: Barthel index score
timeFrame: six month post randomization
Secondary outcomes:
measure: NIHSS score and functional status
timeFrame: 3, 6 and 12 months post randomization
Other outcomes:
Locations:
city: New Delhi
country: India
facility: All India Institute of Medical Sciences
state: Delhi
city: New Delhi
country: India
facility: Army Hospital (R & R Hospital)
state: Delhi
city: Chandigarh
country: India
facility: Post Graduate Institute of Medical Education and Research
state: Haryana
city: Pune
country: India
facility: Armed Forces Medical College
state: Maharastra
city: Lucknow
country: India
facility: Sanjay Gandhi Postgraduate Institute of Medical Sciences
state: UttarPradesh
Study officials:
affiliation: All India Institute of Medical Sciences
name: Dr. Kameshwar Prasad, MBBS, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Sanjay Gandhi Postgraduate Institute of Medical Sciences
name: Dr. Usha Kant Misra, MBBS, MD, DM
role: PRINCIPAL_INVESTIGATOR
affiliation: Armed Forces Medical College
name: Dr. R.S Sarkar
role: PRINCIPAL_INVESTIGATOR
affiliation: Post Graduate Institute of Medical Education and Research, Chandigarh
name: Dr. Sudesh Kumar Prabhakar, MBBS, MD, DM
role: PRINCIPAL_INVESTIGATOR
affiliation: Army R & R Hospital
name: Dr. Sharat Joshi, MBBS,MD, DM
role: PRINCIPAL_INVESTIGATOR
References:
citation: Prasad K, Sharma A, Garg A, Mohanty S, Bhatnagar S, Johri S, Singh KK, Nair V, Sarkar RS, Gorthi SP, Hassan KM, Prabhakar S, Marwaha N, Khandelwal N, Misra UK, Kalita J, Nityanand S; InveST Study Group. Intravenous autologous bone marrow mononuclear stem cell therapy for ischemic stroke: a multicentric, randomized trial. Stroke. 2014 Dec;45(12):3618-24. doi: 10.1161/STROKEAHA.114.007028. Epub 2014 Nov 6.
citation: Prasad K, Mohanty S, Bhatia R, Srivastava MV, Garg A, Srivastava A, Goyal V, Tripathi M, Kumar A, Bal C, Vij A, Mishra NK. Autologous intravenous bone marrow mononuclear cell therapy for patients with subacute ischaemic stroke: a pilot study. Indian J Med Res. 2012 Aug;136(2):221-8.