Safety/Efficacy Study for the Treatment of Amyotrophic Lateral Sclerosis

Study Overview
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Brief Summary
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A Phase I, single center, prospective, non-randomized, open label, safety/efficacy study of the infusion of autologous bone marrow-derived stem cells, in 6 patients with Amyotrophic Lateral Sclerosis according to established criteria (1), (2) with a moderate to severe diagnosis of ALS according to the World Federation of Neurology El Escorial criteria. The primary purpose of this study is to evaluate safety of the infusion procedure, as assessed by absence of complications at the site of infusion or the appearance of new neurologic deficit not attributed to the natural progression of the disease. Secondary outcomes will include a)neurological evidence of trends toward a slowing down of the decline of the forced vital capacity (FVC) (3) and of the functional rating scale (ALS-FRS) scores, as assessed at 3-month intervals, b)evidence of a decline of the maximum voluntary isometric contraction-arm (MVIC-arm) and MVIC-grip Z (4) scores and c)patient evaluation that the treatment was effective and consider the possibility of a new cell product stem cell infusion. Subjects who fulfill inclusion/exclusion criteria and sign informed consent will undergo an aspiration of bone marrow from the iliac crest for preparation of the cellular product. The day of infusion, the investigational product will be injected into the patient's intrathecal space. After cell infusion patients will be followed at WK 2, MN 1, MN 2, MN 6 and a long-term followup at MN 12 in the clinic and/or office. Electromyographic (EMG) studies, Forced vital capacity (FVC), functional rating scale (FRS) and maximum voluntary isometric contraction-arm (MVIC-arm) and MVIC-grip Z scores will have been used to assess the status of the disease before (historical record acceptable if done within three months of Screening Visit) and during the 12-month study period after cell infusion.

Official Title
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Phase I, Single Center, Prospective, Non-randomized, Open Label, Safety/Efficacy Study of the Infusion of Autologous Bone Marrow-derived Stem Cells, in Patients With Amyotrophic Lateral Sclerosis

Conditions
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Amyotrophic Lateral Sclerosis

Intervention / Treatment
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* Biological: autologous bone marrow-derived stem cells


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adult male and female subjects > 18 years of age. Good understanding of the protocol and willingness to consent. Moderate to severe Diagnosis of ALS according to the World Federation of Neurology El Escorial criteria. Vital capacity at least 50% predicted value for gender, height and age. More than 6 and less than 36 months of evolution of the disease. Hematocrit greater than 30 % prior to bone marrow aspiration. Platelet count greater than 100 Thousand/uL at screening. INR less than or equal to 1.5. Exclusion Criteria: Any concurrent illness, which affects the bone marrow. Any concomitant medication that affects the bone marrow. Previous stem cell therapy. Any lymphoproliferative disease. Riluzole with 4 weeks of study entry and at any time during the study. Hemophiliacs or subjects with bleeding disorders. Known hypersensitivity to fetal bovine serum HIV infection. Serum creatinine > 3.0 in subjects not on hemodialysis. Skin infection at the infusion site or systemic infection Current smoker. Active drug or alcohol addiction Pregnant, planning to become pregnant or not on accepted birth control method if subject is of child bearing potential. Subjects that are breast feeding. Any condition that the Principal Investigator considers would render the subject unfit for the study.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 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: Diagnostic
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Safety<br>infusion of autologous bone marrow-derived stem cells | Biological: autologous bone marrow-derived stem cells<br>* All patients will receive a unique one-time intrathecal infusion of the cell product suspended in infusion medium.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety | Safety of the infusion procedure, as assessed by absence of complications at the site of infusion or the appearance of new neurologic deficit not attributed to the natural progression of the disease. | one year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Efficacy | Neurological evidence of trends toward a slowing down of the decline of the forced vital capacity and of the functional rating scale scores, as assessed at 3 month intervals. Evidence of a decline of the maximum voluntary isometric contraction-arm (MVIC-arm) and MVIC-grip Z scores. Patient evaluation that the treatment was effective. | one year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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ALS, Lou Gehrig's Disease