A Dose-escalation Safety Trial for Intrathecal Autologous Mesenchymal Stem Cell Therapy in Amyotrophic Lateral Sclerosis

Study Overview
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Brief Summary
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The purpose of this study is to determine determine the safety of intraspinal delivery of mesenchymal stem cells (MSCs) to the cerebral spinal fluid of patients with Amyotrophic Lateral Sclerosis (ALS) using a dose-escalation study.

Detailed Description
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The primary objective of this study is to determine the safety of intrathecal delivery of autologous mesenchymal stem cells (MSCs) to the cerebrospinal fluid (CSF) of patients with ALS using a dose-escalation study. The trial will include 25 adult, non-ventilator-dependent patients with clinically definite amyotrophic lateral sclerosis (ALS). Cells will be isolated from adipose tissue, expanded ex vivo and then, after  8 weeks, intrathecal (IT) autologous delivery of MSCs will be performed. There will be 5 treatment groups of up to 5 patients each. Groups 1, 2, and 4 will receive a single dose of cells. Groups 3 and 5 will receive 2 doses of cells separated by 1 month. Groups will be completed sequentially so that patients will not be enrolled into the next treatment group until at least 3 patients in the preceding group have completed the treatment and 1 month of additional observation without significant toxicity. All patients will be followed on a regular basis until death or for a minimum of 2 years after completion of the final infusion. Initial clinical follow-up will be weekly with scheduled blood, CSF and magnetic resonance imaging (MRI) evaluations. After 1 month, patients will have clinical evaluations at 3 month intervals, or earlier if indicated by clinical status. Addendum: Five subjects from the Group 5 dosing level will received additional injections of MSCs in an extension of the original study, if tolerated.

Official Title
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A Dose-escalation Safety Trial for Intrathecal Autologous Mesenchymal Stem Cell Therapy in Amyotrophic Lateral Sclerosis

Conditions
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Amyotrophic Lateral Sclerosis

Intervention / Treatment
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* Biological: autologous mesenchymal stem cells


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: All patients must have clinically-defined ALS as defined by the World Federation of Neurology criteria Age greater than 18 years If female, must be post-menopausal or had a hysterectomy Permanent resident or citizen of the United States History of a chronic onset of a progressive motor weakness of greater than one year, but less than two years duration Must have vital capacity greater than 65% of predicated for age, gender, and body type Able to comply with protocol requirements, including MRI testing Can provide written informed consent Exclusion Criteria: Any clinically significant medical condition (e.g., within six months of baseline, had myocardial infarction, angina pectoris, and/or congestive heart failure) that, in the opinion of the investigator, would compromise the safety of patient. Autoimmunity, including Crohn's disease, rheumatoid arthritis, psoriasis Malignancy including melanoma with the exception of localized skin cancers (with no evidence of metastasis, significant invasion, or re-occurrence within three years of baseline). Any other malignancy will not be allowed. Active systemic or local infection near the lumbar puncture site Other active systemic disease as defined by laboratory abnormalities Use of herbal medications or other unapproved drugs Enrolled in an investigational drug trial within 30 days of baseline visit Kokmen Short Test of Mental Status score <32 Beck's Depression Inventory score >18 Presence of a tracheostomy Ventilator dependent

Ages Eligible for Study
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Minimum Age: 18 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: Autologous Mesenchymal Stem Cells<br> | Biological: autologous mesenchymal stem cells<br>* There will be five treatment groups of up to five patients each. Groups 1, 2 and 4 will receive a single dose of cells. Groups 3 and 5 will receive 2 doses of cells separated by one month. Intrathecal injections into new subjects will be timed so that there is a minimum of one week between subject injections. The cell dose per group is as follows: Group 1: single intrathecal dose of 1 x 107 cells Group 2: single intrathecal dose of 5 x 107 cells Group 3: one intrathecal dose of 5 x 107 cells followed one month later by a second intrathecal dose of 5 x 107 cells Group 4: single intrathecal dose of 1 x 108 cells Group 5: one intrathecal dose of 1 x 108 cells followed one month later by a second intrathecal dose of 1 x 108 cells<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of patients with dose-limiting toxicities |  | baseline -2 years after completion of the final infusion | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of patients with adverse events |  | baseline -2 years after completion of the final infusion | 
| Change in serum sedimentation rate |  | baseline, 2 years after completion of the final infusion | 
| Change in C-reactive protein levels |  | baseline, 2 years after completion of the final infusion | 
| Change in complete blood counts |  | baseline, 2 years after completion of the final infusion | 
| Change in total nucleated cell count in cerebrospinal fluid (CSF) |  | baseline, 2 years after completion of the final infusion | 
| Change in protein level in cerebrospinal fluid (CSF) |  | baseline, 2 years after completion of the final infusion | 
| Number of patients with presence of cancer cells in their cerebrospinal fluid (CSF) |  | baseline -2 years after completion of the final infusion |