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

Phase 1

Completed

Brief Summary: 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: 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.

Recruitment & Eligibility

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

Arm && Interventions

Group	Intervention	Description
Autologous Mesenchymal Stem Cells	autologous mesenchymal stem cells	-

Primary Outcome Measures

Name	Time	Method
Number of patients with dose-limiting toxicities	baseline -2 years after completion of the final infusion

Secondary Outcome Measures

Name	Time	Method
Change in protein level in cerebrospinal fluid (CSF)	baseline, 2 years after completion of the final infusion
Number of patients with adverse events	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 serum sedimentation rate	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
Number of patients with presence of cancer cells in their cerebrospinal fluid (CSF)	baseline -2 years after completion of the final infusion

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