Study of Two Intrathecal Doses of Autologous Mesenchymal Stem Cells for Amyotrophic Lateral Sclerosis

Study Overview
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Brief Summary
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The study aims to evaluate primarily safety of two injections of autologous mesenchymal stem cells in Amyotrophic Lateral Sclerosis patients. Secondary outcomes of efficacy will also be evaluated

Detailed Description
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The study is an open-label, unmasked, uncontrolled phase I and II trial to evaluate safety and efficacy of two injections of autologous mesenchymal stem cells (MSC) in Amyotrophic Lateral Sclerosis (ALS) patients. Patients will be recruited trough a web-based registration system, open for all ALS Brazilian patients. The patients will be enrolled after in-person screening at the University of Sao Paulo Medical School Clinics Hospital and inclusion criteria fulfilled. There will be 9 national calls for registration, two months apart each. The enrolled patients will be followed for 3 months before bone marrow aspiration (BMA). Patients will receive 2 intrathecal MSC injections, 1 and 2 months after BMA. The patients will be followed for 6 months after the interventions.

Conditions
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AMYOTROPHIC LATERAL SCLEROSIS

Intervention / Treatment
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* Other: Two intrathecal MSC injections


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age between 18 and 70 Possible, probable or definite ALS following El Escorial Revised Criteria (Brooks, 2000) ALSFRS-r ≥30 at enrollment Forced Vital Capacity ≥65% of the height and weight standard No-pregnancy agreement Regional accessibility to the study site Capability to give away agreed consensus Patients will be followed at Academic Institutions at their hometown Exclusion Criteria: Previous cellular therapy Incapacity to lay still during bone marrow aspirate or intrathecal MSC injections Personal history of auto-Immune, myeloproliferative or myelodysplastic diseases, leukemia, lymphoma, whole-body irradiation, hip fracture, severe scoliosis or incapacity to undergo any of the study's proposed procedures Any other disease that may interfere with the study Any other neurological diseases Aspartate or alanine aminotransferases elevated >3x normality upper limit Serum creatinine >2x normality upper limit Hepatitis B and C, HIV, HTLV I and II and syphilis Immunosuppressant drug use within 6 weeks from the study's screening Pregnancy or breast-feeding Acquired or inherited Immunodeficiency Participation in other clinical trials Non-invasive ventilation, tracheostomy or diaphragm pacing Substance abuse within one year and other unstable mental health diseases according to researcher's judgement Gastrostomy or any alternative feeding means Inappropriate in-vitro MSC expansion

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: MSC injection<br>Patients will be followed for 3 months before bone marrow aspiration (BMA). Patients will receive 2 intrathecal MSC injections, 1 and 2 months after BMA. The patients will be followed for 6 months after the interventions. | Other: Two intrathecal MSC injections<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety | Clinical and laboratory monitoring of possible reactions to intrathecal MSC delivery | 10 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Amyotrophic Lateral Sclerosis Functional Rating Scale Revised (ALSFRS-R) | Specific scale for assessing ALS disease progression | 10 months | 
| Change in Handheld dynamometry |  | 10 months | 
| Change in Electrical Impedance Myography |  | 10 months | 
| Change in Forced Vital Capacity (FVC) |  | 10 months | 
| Change in Isometric Strength |  | 10 months | 
| Changes in morphometric parameters of MRI of encephalon and spinal cord |  | 10 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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intrathecal, ALS, mesenchymal stem cells