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Mesenchymal Stem Cell Therapy in Multiple System Atrophy

Primary Purpose

MSA

Status
Active
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Autologous Mesenchymal Stem Cells
Autologous Mesenchymal Stem Cells
Autologous Mesenchymal Stem Cells
Autologous Mesenchymal Stem Cells
Autologous Mesenchymal Stem Cells
Sponsored by
Mayo Clinic
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for MSA

Eligibility Criteria

30 Years - 80 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Mayo Clinic in Rochester

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm Type

Experimental

Experimental

Experimental

Experimental

Experimental

Arm Label

1 dose of 1 × 10(7) MSCs

2 doses of 5 × 10(7) MSCs

2 doses of 1 × 10(8) MSCs

10 doses of 5 x 10(7) (±20%) MSCs

10 doses of 2.5 x 10(7) (±20%) MSCs

Arm Description

Group 1: Participants will receive a single intrathecal dose of 1 × 10(7) mesenchymal stem cells (MSCs)

Group 2: Participants will receive one intrathecal dose of 5 × 10(7) mesenchymal stem cells (MSCs), followed by a second intrathecal dose of 5 × 10(7) MSCs approximately one month later

Group 3: Participants will receive one intrathecal dose of 1 × 10(8) mesenchymal stem cells (MSCs), followed by a second intrathecal dose of 1 × 10(8) MSCs approximately one month later

Group 4: Participants will receive up to 10 doses of 5 x 10(7) (±20%) mesenchymal stem cells (MSCs) approximately 6 months apart.

Group 5: Participants will receive up to 10 doses of 2.5 x 10(7) (±20%) mesenchymal stem cells (MSCs) approximately 6 months apart.

Outcomes

Primary Outcome Measures

Adverse event frequency (by severity, type, attribution, and intervention dose).

Secondary Outcome Measures

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).
Rate of change from baseline to 12 months (or last available date) in UMSARS II score.
Rate of change from baseline to 12 months (or last available date) in UMSARS total score.
Rate of change in COMPASS-select score from baseline to 12 months.
Change in CASS score and thermoregulatory sweat test (TST) % from baseline to 12 months.
MRI morphometric changes using dedicated algorithms to evaluate rate of atrophy of defined areas of brain from baseline to 12 months.
Change in CSF biomarkers from baseline to 2 months.

Full Information

First Posted
October 31, 2014
Last Updated
September 13, 2023
Sponsor
Mayo Clinic
Collaborators
Food and Drug Administration (FDA), National Institute of Neurological Disorders and Stroke (NINDS)
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1. Study Identification

Unique Protocol Identification Number
NCT02315027
Brief Title
Mesenchymal Stem Cell Therapy in Multiple System Atrophy
Official Title
Intrathecal Autologous Mesenchymal Stem Cell Therapy in Multiple System Atrophy (MSA) - Effect of Dose and Natural History
Study Type
Interventional

2. Study Status

Record Verification Date
September 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
October 2012 (undefined)
Primary Completion Date
March 2024 (Anticipated)
Study Completion Date
March 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Mayo Clinic
Collaborators
Food and Drug Administration (FDA), National Institute of Neurological Disorders and Stroke (NINDS)

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
MSA

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Sequential Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
30 (Actual)

8. Arms, Groups, and Interventions

Arm Title
1 dose of 1 × 10(7) MSCs
Arm Type
Experimental
Arm Description
Group 1: Participants will receive a single intrathecal dose of 1 × 10(7) mesenchymal stem cells (MSCs)
Arm Title
2 doses of 5 × 10(7) MSCs
Arm Type
Experimental
Arm Description
Group 2: Participants will receive one intrathecal dose of 5 × 10(7) mesenchymal stem cells (MSCs), followed by a second intrathecal dose of 5 × 10(7) MSCs approximately one month later
Arm Title
2 doses of 1 × 10(8) MSCs
Arm Type
Experimental
Arm Description
Group 3: Participants will receive one intrathecal dose of 1 × 10(8) mesenchymal stem cells (MSCs), followed by a second intrathecal dose of 1 × 10(8) MSCs approximately one month later
Arm Title
10 doses of 5 x 10(7) (±20%) MSCs
Arm Type
Experimental
Arm Description
Group 4: Participants will receive up to 10 doses of 5 x 10(7) (±20%) mesenchymal stem cells (MSCs) approximately 6 months apart.
Arm Title
10 doses of 2.5 x 10(7) (±20%) MSCs
Arm Type
Experimental
Arm Description
Group 5: Participants will receive up to 10 doses of 2.5 x 10(7) (±20%) mesenchymal stem cells (MSCs) approximately 6 months apart.
Intervention Type
Biological
Intervention Name(s)
Autologous Mesenchymal Stem Cells
Intervention Description
single dose of 1 × 10(7) cells intrathecally
Intervention Type
Biological
Intervention Name(s)
Autologous Mesenchymal Stem Cells
Intervention Description
2 doses of 5 × 10(7) cells intrathecally each 1 month (±4 days) apart
Intervention Type
Biological
Intervention Name(s)
Autologous Mesenchymal Stem Cells
Intervention Description
2 doses of 1 × 10(8) cells intrathecally each 1 month apart
Intervention Type
Biological
Intervention Name(s)
Autologous Mesenchymal Stem Cells
Intervention Description
Ten doses of 5 x 10(7) (±20%) cells intrathecally six months (±1 month) apart
Intervention Type
Biological
Intervention Name(s)
Autologous Mesenchymal Stem Cells
Intervention Description
Ten doses of 2.5 x 10(7) (±20%) cells intrathecally six months (±1 month) apart
Primary Outcome Measure Information:
Title
Adverse event frequency (by severity, type, attribution, and intervention dose).
Time Frame
14 months
Secondary Outcome Measure Information:
Title
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
Title
Rate of change from baseline to 12 months (or last available date) in UMSARS II score.
Time Frame
12 months
Title
Rate of change from baseline to 12 months (or last available date) in UMSARS total score.
Time Frame
12 months
Title
Rate of change in COMPASS-select score from baseline to 12 months.
Time Frame
12 months
Title
Change in CASS score and thermoregulatory sweat test (TST) % from baseline to 12 months.
Time Frame
12 months
Title
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
Title
Change in CSF biomarkers from baseline to 2 months.
Time Frame
2 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
30 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria 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%). Participants who are less than 4 years from the time of documented MSA diagnosis. Participants with an anticipated survival of at least 3 years in the opinion of the investigator. Participants who are willing and able to give informed consent. "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: 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. 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). Participants with malignant neoplasms. Participants who have taken any investigational products within 60 days prior to baseline. 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. Diseases with features of Parkinsons Disease; e.g., diffuse Lewy body disease, progressive supranuclear palsy, essential tremor, hereditary olivopontocerebellar atrophy, or postencephalitic parkinsonism. Dementia (DSM-IV criteria - American Psychiatric Association 1994). The score on the Mini-Mental State Examination must be >24. History of electroconvulsive therapy. History of brain surgery for Parkinsons disease. Patients with contraindication for MRI scanning, including those with MRI-incompatible pacemakers Patients with active systemic infection or local infection, which is close to the spinal injection site
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Wolfgang Singer, MD
Organizational Affiliation
Mayo Clinic
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Phillip Low, MD
Organizational Affiliation
Mayo Clinic
Official's Role
Principal Investigator
Facility Information:
Facility Name
Mayo Clinic in Rochester
City
Rochester
State/Province
Minnesota
ZIP/Postal Code
55905
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
27515308
Citation
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.
Results Reference
derived
Links:
URL
https://www.mayo.edu/research/clinical-trials
Description
Mayo Clinic Clinical Trials

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Mesenchymal Stem Cell Therapy in Multiple System Atrophy

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