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

This study is currently recruiting participants. (see Contacts and Locations)
Verified August 2014 by Mayo Clinic
Sponsor:
Information provided by (Responsible Party):
Anthony J. Windebank, Mayo Clinic
ClinicalTrials.gov Identifier:
NCT01609283
First received: May 18, 2012
Last updated: August 7, 2014
Last verified: August 2014
  Purpose

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.


Condition Intervention Phase
Amyotrophic Lateral Sclerosis
Biological: autologous mesenchymal stem cells
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Dose-escalation Safety Trial for Intrathecal Autologous Mesenchymal Stem Cell Therapy in Amyotrophic Lateral Sclerosis

Resource links provided by NLM:


Further study details as provided by Mayo Clinic:

Primary Outcome Measures:
  • Number of patients with dose-limiting toxicities [ Time Frame: baseline -2 years after completion of the final infusion ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Number of patients with adverse events [ Time Frame: baseline -2 years after completion of the final infusion ] [ Designated as safety issue: Yes ]
  • Change in serum sedimentation rate [ Time Frame: baseline, 2 years after completion of the final infusion ] [ Designated as safety issue: Yes ]
  • Change in C-reactive protein levels [ Time Frame: baseline, 2 years after completion of the final infusion ] [ Designated as safety issue: Yes ]
  • Change in complete blood counts [ Time Frame: baseline, 2 years after completion of the final infusion ] [ Designated as safety issue: Yes ]
  • Change in total nucleated cell count in cerebrospinal fluid (CSF) [ Time Frame: baseline, 2 years after completion of the final infusion ] [ Designated as safety issue: Yes ]
  • Change in protein level in cerebrospinal fluid (CSF) [ Time Frame: baseline, 2 years after completion of the final infusion ] [ Designated as safety issue: Yes ]
  • Number of patients with presence of cancer cells in their cerebrospinal fluid (CSF) [ Time Frame: baseline -2 years after completion of the final infusion ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 25
Study Start Date: May 2012
Estimated Study Completion Date: December 2014
Estimated Primary Completion Date: December 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01609283

Locations
United States, Minnesota
Mayo Clinic Recruiting
Rochester, Minnesota, United States, 55905
Contact: ALS Study Team    507-284-2676    rstalsresearch@mayo.edu   
Contact: Nathan P. Staff, MD, PhD    507-284-2511    rstalsresearch@mayo.edu   
Principal Investigator: Anthony J. Windebank, MD         
Principal Investigator: Nathan P. Staff, MD, PhD         
Sponsors and Collaborators
Mayo Clinic
  More Information

No publications provided

Responsible Party: Anthony J. Windebank, Principal Investigator, Mayo Clinic
ClinicalTrials.gov Identifier: NCT01609283     History of Changes
Other Study ID Numbers: 11-008415
Study First Received: May 18, 2012
Last Updated: August 7, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Amyotrophic Lateral Sclerosis
Motor Neuron Disease
Sclerosis
Central Nervous System Diseases
Metabolic Diseases
Nervous System Diseases
Neurodegenerative Diseases
Neuromuscular Diseases
Pathologic Processes
Proteostasis Deficiencies
Spinal Cord Diseases
TDP-43 Proteinopathies

ClinicalTrials.gov processed this record on November 20, 2014