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

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ClinicalTrials.gov Identifier: NCT01609283
Recruitment Status : Completed
First Posted : May 31, 2012
Last Update Posted : September 2, 2019
Sponsor:
Information provided by (Responsible Party):
Anthony J. Windebank, Mayo Clinic

Tracking Information
First Submitted Date  ICMJE May 18, 2012
First Posted Date  ICMJE May 31, 2012
Last Update Posted Date September 2, 2019
Study Start Date  ICMJE May 2012
Actual Primary Completion Date January 31, 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 27, 2013)
Number of patients with dose-limiting toxicities [ Time Frame: baseline -2 years after completion of the final infusion ]
Original Primary Outcome Measures  ICMJE
 (submitted: May 29, 2012)
Number of patients with dose-limiting toxicities [ Time Frame: 2 years after completion of the final infusion ]
Change History Complete list of historical versions of study NCT01609283 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: June 27, 2013)
  • Number of patients with adverse events [ Time Frame: baseline -2 years after completion of the final infusion ]
  • Change in serum sedimentation rate [ Time Frame: baseline, 2 years after completion of the final infusion ]
  • Change in C-reactive protein levels [ Time Frame: baseline, 2 years after completion of the final infusion ]
  • Change in complete blood counts [ Time Frame: baseline, 2 years after completion of the final infusion ]
  • Change in total nucleated cell count in cerebrospinal fluid (CSF) [ Time Frame: baseline, 2 years after completion of the final infusion ]
  • Change in protein level in cerebrospinal fluid (CSF) [ Time Frame: baseline, 2 years after completion of the final infusion ]
  • Number of patients with presence of cancer cells in their cerebrospinal fluid (CSF) [ Time Frame: baseline -2 years after completion of the final infusion ]
Original Secondary Outcome Measures  ICMJE
 (submitted: May 29, 2012)
  • Number of patients with adverse events [ Time Frame: 2 years after completion of the final infusion ]
  • Change in serum sedimentation rate [ Time Frame: baseline, 2 years after completion of the final infusion ]
  • Change in C-reactive protein levels [ Time Frame: baseline, 2 years after completion of the final infusion ]
  • Change in complete blood counts [ Time Frame: baseline, 2 years after completion of the final infusion ]
  • Change in total nucleated cell count in cerebrospinal fluid (CSF) [ Time Frame: baseline, 2 years after completion of the final infusion ]
  • Change in protein level in cerebrospinal fluid (CSF) [ Time Frame: baseline, 2 years after completion of the final infusion ]
  • Number of patients with presence of cancer cells in their cerebrospinal fluid (CSF) [ Time Frame: 2 years after completion of the final infusion ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Dose-escalation Safety Trial for Intrathecal Autologous Mesenchymal Stem Cell Therapy in Amyotrophic Lateral Sclerosis
Official Title  ICMJE A Dose-escalation Safety Trial for Intrathecal Autologous Mesenchymal Stem Cell Therapy in Amyotrophic Lateral Sclerosis
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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Amyotrophic Lateral Sclerosis
Intervention  ICMJE 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
Study Arms  ICMJE Experimental: Autologous Mesenchymal Stem Cells
Intervention: Biological: autologous mesenchymal stem cells
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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: December 29, 2015)
27
Original Estimated Enrollment  ICMJE
 (submitted: May 29, 2012)
25
Actual Study Completion Date  ICMJE January 31, 2019
Actual Primary Completion Date January 31, 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01609283
Other Study ID Numbers  ICMJE 11-008415
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Anthony J. Windebank, Mayo Clinic
Study Sponsor  ICMJE Mayo Clinic
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Anthony Windebank, MD Mayo Clinic
PRS Account Mayo Clinic
Verification Date August 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP