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Mesenchymal Stem Cell Therapy in Multiple System Atrophy

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02315027
Recruitment Status : Active, not recruiting
First Posted : December 11, 2014
Last Update Posted : November 6, 2020
Sponsor:
Information provided by (Responsible Party):
Phillip Low, Mayo Clinic

Tracking Information
First Submitted Date  ICMJE October 31, 2014
First Posted Date  ICMJE December 11, 2014
Last Update Posted Date November 6, 2020
Study Start Date  ICMJE October 2012
Estimated Primary Completion Date August 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: December 9, 2014)
Adverse event frequency (by severity, type, attribution, and intervention dose). [ Time Frame: 14 months ]
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: December 9, 2014)
  • Rate of change of Unified Multiple System Atrophy Rating Scale (UMSARS) I score from baseline to 12 months (or last available date), compared with placebo limb of Rifampicin trial (historical control cohort). [ Time Frame: 12 months ]
  • Rate of change from baseline to 12 months (or last available date) in UMSARS II score. [ Time Frame: 12 months ]
  • Rate of change from baseline to 12 months (or last available date) in UMSARS total score. [ Time Frame: 12 months ]
  • Rate of change in COMPASS-select score from baseline to 12 months. [ Time Frame: 12 months ]
  • Change in CASS score and thermoregulatory sweat test (TST) % from baseline to 12 months. [ Time Frame: 12 months ]
  • MRI morphometric changes using dedicated algorithms to evaluate rate of atrophy of defined areas of brain from baseline to 12 months. [ Time Frame: 12 months ]
  • Change in CSF biomarkers from baseline to 2 months. [ Time Frame: 2 months ]
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Mesenchymal Stem Cell Therapy in Multiple System Atrophy
Official Title  ICMJE Intrathecal Autologous Mesenchymal Stem Cell Therapy in Multiple System Atrophy (MSA) - Effect of Dose and Natural History
Brief Summary The purpose of this study is to determine whether mesenchymal stem cells (MSCs) can be safely delivered to the cerebrospinal fluid (CSF) of patients with multiple system atrophy (MSA). Funding Source - FDA OOPD.
Detailed Description The primary aim is to evaluate the safety and tolerability of intrathecal injection of autologous MSCs in a dose escalation study in patients with MSA. Safety secondary goals include to monitor changes in peripheral blood and in components of CSF, and monitor for any changes of nervous system structures using MRI. Efficacy secondary goals include evaluating potential efficacy by providing a number of studies and instruments that will detect changes in the course of the disease in terms of autonomic and neurologic symptoms and deficits.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE MSA
Intervention  ICMJE Biological: autologous mesenchymal stem cells

There will be three treatment groups of up to 8 patients each. Groups 1 will receive a single dose of cells. Groups 2 and 3 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: one intrathecal dose of 5 x 107 cells followed one month (+/- 4 days) later by a second intrathecal dose of 5 x 107 cells.
  • Group 3: one intrathecal dose of 1 x 108 cells followed one month (+/- 4 days) later by a second intrathecal dose of 1 x 108 cells.
Study Arms  ICMJE Experimental: autologous mesenchymal stem cells
Administration of 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 Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: May 8, 2017)
30
Original Actual Enrollment  ICMJE
 (submitted: December 9, 2014)
24
Estimated Study Completion Date  ICMJE August 2021
Estimated Primary Completion Date August 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria

  1. Participants aged 30-80 years old with a diagnosis of MSA based on clinical criteria and standardized autonomic testing. This approach allows for identification of patients with MSA with very high specificity and is yet sensitive enough to allow for enrollment of patients at a disease stage at which an intervention on the natural disease course has a meaningful impact on patient outcome. Patients therefore have to fulfill Gilman Criteria (2000) for probable MSA of the parkinsonian subtype (MSA-P) or cerebellar subtype (MSA-C) and have findings on autonomic function testing suggestive of MSA (CASS ≥5 or a TST% ≥25%).
  2. Participants who are less than 4 years from the time of documented MSA diagnosis.
  3. Participants with an anticipated survival of at least 3 years in the opinion of the investigator.
  4. Participants who are willing and able to give informed consent.
  5. "Normal" cognition as assessed by Mini-Mental State Examination (MMSE). We will require a value >24.

Exclusion Criteria

Any of the following conditions will exclude the participant from entering the study:

  1. Women of childbearing potential who do not practice an acceptable method of birth control. Acceptable methods of birth control in this study are: surgical sterilization, intrauterine devices, partner's vasectomy, a double-protection method (condom or diaphragm with spermicide), hormonal contraceptive drug (i.e., oral contraceptive, contraceptive patch, long-acting injectable contraceptive) with a required second mode of contraception.
  2. Participants with a clinically significant or unstable medical or surgical condition that, in the opinion of the investigator, might preclude safe completion of the study or might affect the results of the study. These include conditions causing significant central nervous system (CNS) or autonomic dysfunction, including congestive heart failure, recent (<6 months) myocardial infarct, cardiopulmonary disease, severe, uncontrolled hypertension, thrombocytopenia (<50 x 10(9)/L), severe anemia (<8g/dl), immunocompromised state, liver or kidney disease (creatinine >2.3mg/dl), uncontrolled diabetes mellitus (HbA1c >10g%), alcoholism, amyloidosis, uncontrolled hypothyroidism, sympathectomy, unstable peripheral neuropathies, concurrent infections, orthopedic problems that compromise mobility and activity of daily living, cerebrovascular accidents, neurotoxin or neuroactive drug exposure, parkinsonism due to drugs (including neuroleptics, alpha-methyldopa, reserpine, metoclopramide).
  3. Participants with malignant neoplasms.
  4. Participants who have taken any investigational products within 60 days prior to baseline.
  5. Medications that could affect autonomic function. If patients are taking those medications, those will be suspended prior to autonomic testing. Therapy with midodrine, anticholinergic, alpha and beta adrenergic antagonists or other medications that affect autonomic function will be withdrawn 48 hours prior to autonomic evaluations. Fludrocortisone doses up to 0.2 mg per day will be permitted.
  6. Diseases with features of Parkinsons Disease; e.g., diffuse Lewy body disease, progressive supranuclear palsy, essential tremor, hereditary olivopontocerebellar atrophy, or postencephalitic parkinsonism.
  7. Dementia (DSM-IV criteria - American Psychiatric Association 1994). The score on the Mini-Mental State Examination must be >24.
  8. History of electroconvulsive therapy.
  9. History of brain surgery for Parkinsons disease.
  10. Patients with contraindication for MRI scanning, including those with MRI-incompatible pacemakers
  11. Patients with active systemic infection or local infection, which is close to the spinal injection site
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 30 Years to 80 Years   (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 NCT02315027
Other Study ID Numbers  ICMJE 12-005950
G4789 ( Other Grant/Funding Number: FDA - OOPD )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Phillip Low, Mayo Clinic
Study Sponsor  ICMJE Mayo Clinic
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Phillip Low, MD Mayo Clinic
Principal Investigator: Wolfgang Singer, MD Mayo Clinic
PRS Account Mayo Clinic
Verification Date November 2020

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