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

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.

Study Overview

• Status: Completed
• Conditions: Amyotrophic Lateral Sclerosis
• Intervention / Treatment: Biological: autologous mesenchymal stem cells

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.

• Study Type: Interventional
• Enrollment (Actual): 27
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Autologous Mesenchymal Stem Cells

Biological: autologous mesenchymal stem cells; 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

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	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

Collaborators and Investigators

• Sponsor: Mayo Clinic
• Investigators: Principal Investigator: Anthony Windebank, MD, Mayo Clinic

Publications and helpful links

General Publications

• Camilleri ET, Gustafson MP, Dudakovic A, Riester SM, Garces CG, Paradise CR, Takai H, Karperien M, Cool S, Sampen HJ, Larson AN, Qu W, Smith J, Dietz AB, van Wijnen AJ. Identification and validation of multiple cell surface markers of clinical-grade adipose-derived mesenchymal stromal cells as novel release criteria for good manufacturing practice-compliant production. Stem Cell Res Ther. 2016 Aug 11;7(1):107. doi: 10.1186/s13287-016-0370-8.

Helpful Links

• Mayo Clinic Clinical Trials

Study record dates

Study Major Dates

• Study Start: May 1, 2012
• Primary Completion (Actual): January 31, 2019
• Study Completion (Actual): January 31, 2019

Study Registration Dates

• First Submitted: May 18, 2012
• First Submitted That Met QC Criteria: May 29, 2012
• First Posted (Estimate): May 31, 2012

Study Record Updates

• Last Update Posted (Actual): September 3, 2019
• Last Update Submitted That Met QC Criteria: August 29, 2019
• Last Verified: August 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Metabolic Diseases; Central Nervous System Diseases; Nervous System Diseases; Neuromuscular Diseases; Neurodegenerative Diseases; Spinal Cord Diseases; TDP-43 Proteinopathies; Proteostasis Deficiencies; Sclerosis; Motor Neuron Disease; Amyotrophic Lateral Sclerosis
• Other Study ID Numbers: 11-008415

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No