Stem Cell Therapy For Acute Ischemic Stroke Patients

NCT ID: NCT02425670

Last Updated: 2015-04-24

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 120 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-01-31
• Study Completion Date: 2011-06-30

Brief Summary

The purpose of this study is to determine whether patients with subacute ischemic stroke will benefit from infusion of patient's own bone marrow derived stem cells.

Primary Hypothesis: Intravenous injection of bone marrow mononuclear cells at a dose of 30 to 500 million in patients with subacute ischemic stroke results in reduction of infarct volume and improvement of neurological function compared to those without the injection.

Secondary Hypothesis: Patients receiving more than 100 million Bone marrow derived stem cells (BMSC) will have better outcome than those receiving fewer dosages of cells.

Detailed Description

Background: Stroke accounts for significant disability and there is need for novel treatment modality which can improve the functional outcome. In this randomized clinical trial, investigators proposed to examine stem cell therapy as a potential therapeutic modality. Stem cells in animal stroke models have shown reduction in infarct size and improvement in neurological function. Only one human clinical trial with intravenous autologous marrow stromal cell therapy of five patients has shown some benefit. The primary objective of this phase II study was to explore if there is favourable risk to benefit ratio for autologous bone marrow derived mononuclear stem cell therapy (BMSCs) in patients with acute ischemic stroke to justify a larger phase III trial.

Methods & Design: The study recruited 120 men and women aged 18-70 years presenting with acute ischemic stroke (7-29 days) and a NIHSS score of ≥ 7 and BI ≤ 50. Following baseline assessment (MRI Brain, Whole Body PET scan, EEG brain, CT scan Brain and clinical examination including National Institute of Health Stroke Scale (NIHSS), Barthel Index (BI), modified Rankin Scale (mRS), Glasgow Come Scale (GCS), participants were randomly allocated to two groups: conventional management alone (control group); or conventional management and autologous intravenous BMSCs transplantation (experimental group). Bone marrow was aspirated under local anaesthesia and the isolated BMSCs cells injected intravenously within 4 hours. The patients were monitored with hemogram & renal/liver function tests, CT scan brain at 36 hrs and clinical examination for a week. The patients were followed up to one year with periodic MRI brain at 3 months, 6 months, EEG & PET scan at 6 months and 1 year. The primary efficacy outcomes were difference between the two groups in the Modified Barthel index score and modified Rankin Scale score at six-month post-randomisation. The secondary efficacy outcomes are: NIHSS score at six-months and 1 year post-randomisation; and the modified Rankin scale score at 3 months and one year post-randomization, and functional status measured by barthel index (in binary scale <60 or >60 ) at six months and one year post-randomization. Dose response analysis were done by comparing outcomes in patients receiving various doses of bone marrow mononuclear cells.

Discussion: This phase 2 study was aimed to explore if there is a favourable risk-to-benefit ratio for stem cell therapy in patients with acute ischemic stroke. Investigators also planned to examine whether there is justification for phase III trial of autologous bone marrow derived mononuclear stem cell therapy for acute ischemic stroke.

Conditions

Middle Cerebral Artery Infarction; Anterior Cerebral Artery Infarction

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Bone marrow derived stem cells (BMSCs)

BMSCs 30-500 million plus conventional management

Group Type: EXPERIMENTAL

BMSCs

Intervention Type: OTHER

30-500 million Autologous BMSCs will be given intravenously to patients with acute ischemic stroke (onset from 7 to less than 30 days).

Control

Control: conventional management

Group Type: NO_INTERVENTION

No interventions assigned to this group

Interventions

BMSCs

30-500 million Autologous BMSCs will be given intravenously to patients with acute ischemic stroke (onset from 7 to less than 30 days).

Intervention Type: OTHER

Other Intervention Names

Stem cell arm

Eligibility Criteria

Inclusion Criteria

Patients will be judged eligible if they have all of the following:

1. Sudden onset of focal neurologic deficit or impairment of consciousness,

2. Computerized tomographic or MRI scan of the head showing no primary haematoma, and relevant lesions within the Middle Cerebral Artery (MCA) and anterior cerebral artery (ACA) territory. Hemorrhagic changes in infarct are acceptable.

3. Age between 18 and 75 years

4. Seven days or more but less than 30 days since the onset of the qualifying event,

5. Glasgow Coma Scale score of above 8 at the time of randomization, in aphasic Eye and Motor score of more than 6,

6. Modified Barthel index score of 50 or less at the time of randomization.

7. NIHSS score of 7 or more points and inability to walk unaided or raise upper limb by 90 °

8. Patient is stable: A patient will be defined as stable when he has normal respiration, is afebrile, has BP less than mean arterial pressure of 125mm Hg (but no hypotension defined as systolic BP <90mmHg), has fasting venous blood sugar level less than 200mg % and normal urea/electrolytes for at least 48 hours.

1. Lacunar syndrome

2. Intubation

3. Posterior Circulation Stroke

4. Co-morbidity likely to limit survival to less than three years e.g. malignant diseases, hepatic or renal failure

5. Pre-stroke disability leading to dependence on others for activities of daily living,

6. Inaccessibility for follow-up

7. Allergy to local anaesthetic

8. Unwillingness to provide written informed consent by self or assent by next of kin.

9. Symptom of Acute myocardial infarction or acute involvement of any other organ.

10. Pregnancy

11. Human immunodeficiency virus (HIV)/hepatitis C virus (HCV)/HbsAg positive.

12. Patient is a part of any other trial.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Ministry of Science and Technology, India

OTHER_GOV

Sponsor Role: collaborator

Army Hospital Research And Referral, India

OTHER

Sponsor Role: collaborator

Armed Forces Medical College, Pune

OTHER

Sponsor Role: collaborator

Post Graduate Institute of Medical Education and Research, Chandigarh

OTHER

Sponsor Role: collaborator

Sanjay Gandhi Postgraduate Institute of Medical Sciences

OTHER_GOV

Sponsor Role: collaborator

All India Institute of Medical Sciences

OTHER

Sponsor Role: lead

Responsible Party

Kameshwar Prasad

Professor and Head, Department of Neurology

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Kameshwar Prasad, MBBS, MD

Role: PRINCIPAL_INVESTIGATOR

All India Institute of Medical Sciences

Locations

Postgraduate Institute of Medical Education & Research

Chandigarh, Chandigarh, India

Armed Forces Medical College

Pune, Maharashtra, India

Army Hospital (Referral and Research Centre),

Delhi Cantonment, National Capital Territory of Delhi, India

All India Institute of Medical Sciences

New Delhi, National Capital Territory of Delhi, India

Sanjay Gandhi Postgraduate Institute of Medical Sciences

Lucknow, Uttar Pradesh, India

Countries

India

References

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.

Reference Type: RESULT

PMID: 25378424 (View on PubMed)

Other Identifiers

REFCTRI000046, 19.04.2008

Identifier Type: OTHER

Identifier Source: secondary_id

BT/pr6815/MED/14/880/2005AIIMS

Identifier Type: -

Identifier Source: org_study_id