Mesenchymal Stem Cell Therapy in Multiple System Atrophy
Intrathecal Autologous Mesenchymal Stem Cell Therapy in Multiple System Atrophy (MSA) - Effect of Dose and Natural History
Study Overview
Status
Status
Conditions
Conditions
Intervention / Treatment
Intervention / Treatment
Detailed Description
Study Type
Study Type
Enrollment (Actual)
Enrollment
Phase
Phase
- Phase 2
- Phase 1
Contacts and Locations
Study Locations
-
-
Minnesota
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Rochester, Minnesota, United States, 55905
- Mayo Clinic in Rochester
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-
Participation Criteria
Eligibility Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
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
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Non-Randomized
- Interventional Model: Sequential Assignment
- Masking: None (Open Label)
Number of Arms
Arms and Interventions
Participant Group / ArmParticipant Group / Arm |
Intervention / TreatmentIntervention / Treatment |
|---|---|
|
Experimental: 1 dose of 1 × 10(7) MSCs
Group 1: Participants will receive a single intrathecal dose of 1 × 10(7) mesenchymal stem cells (MSCs)
|
single dose of 1 × 10(7) cells intrathecally
2 doses of 5 × 10(7) cells intrathecally each 1 month (±4 days) apart
2 doses of 1 × 10(8) cells intrathecally each 1 month apart
Ten doses of 5 x 10(7) (±20%) cells intrathecally six months (±1 month) apart
Ten doses of 2.5 x 10(7) (±20%) cells intrathecally six months (±1 month) apart
|
|
Experimental: 2 doses of 5 × 10(7) 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
|
single dose of 1 × 10(7) cells intrathecally
2 doses of 5 × 10(7) cells intrathecally each 1 month (±4 days) apart
2 doses of 1 × 10(8) cells intrathecally each 1 month apart
Ten doses of 5 x 10(7) (±20%) cells intrathecally six months (±1 month) apart
Ten doses of 2.5 x 10(7) (±20%) cells intrathecally six months (±1 month) apart
|
|
Experimental: 2 doses of 1 × 10(8) MSCs
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
|
single dose of 1 × 10(7) cells intrathecally
2 doses of 5 × 10(7) cells intrathecally each 1 month (±4 days) apart
2 doses of 1 × 10(8) cells intrathecally each 1 month apart
Ten doses of 5 x 10(7) (±20%) cells intrathecally six months (±1 month) apart
Ten doses of 2.5 x 10(7) (±20%) cells intrathecally six months (±1 month) apart
|
|
Experimental: 10 doses of 5 x 10(7) (±20%) MSCs
Group 4: Participants will receive up to 10 doses of 5 x 10(7) (±20%) mesenchymal stem cells (MSCs) approximately 6 months apart.
|
single dose of 1 × 10(7) cells intrathecally
2 doses of 5 × 10(7) cells intrathecally each 1 month (±4 days) apart
2 doses of 1 × 10(8) cells intrathecally each 1 month apart
Ten doses of 5 x 10(7) (±20%) cells intrathecally six months (±1 month) apart
Ten doses of 2.5 x 10(7) (±20%) cells intrathecally six months (±1 month) apart
|
|
Experimental: 10 doses of 2.5 x 10(7) (±20%) MSCs
Group 5: Participants will receive up to 10 doses of 2.5 x 10(7) (±20%) mesenchymal stem cells (MSCs) approximately 6 months apart.
|
single dose of 1 × 10(7) cells intrathecally
2 doses of 5 × 10(7) cells intrathecally each 1 month (±4 days) apart
2 doses of 1 × 10(8) cells intrathecally each 1 month apart
Ten doses of 5 x 10(7) (±20%) cells intrathecally six months (±1 month) apart
Ten doses of 2.5 x 10(7) (±20%) cells intrathecally six months (±1 month) apart
|
What is the study measuring?
Primary Outcome Measures
Primary Outcome Measures
Outcome Measure |
Time Frame |
|---|---|
|
Adverse event frequency (by severity, type, attribution, and intervention dose).
Time Frame: 14 months
|
14 months
|
Secondary Outcome Measures
Secondary Outcome Measures
Outcome Measure |
Time Frame |
|---|---|
|
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
|
12 months
|
|
Rate of change from baseline to 12 months (or last available date) in UMSARS II score.
Time Frame: 12 months
|
12 months
|
|
Rate of change from baseline to 12 months (or last available date) in UMSARS total score.
Time Frame: 12 months
|
12 months
|
|
Rate of change in COMPASS-select score from baseline to 12 months.
Time Frame: 12 months
|
12 months
|
|
Change in CASS score and thermoregulatory sweat test (TST) % from baseline to 12 months.
Time Frame: 12 months
|
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
|
12 months
|
|
Change in CSF biomarkers from baseline to 2 months.
Time Frame: 2 months
|
2 months
|
Collaborators and Investigators
Sponsor
Sponsor
Collaborators
Collaborators
Investigators
Investigators
- Principal Investigator: Wolfgang Singer, MD, Mayo Clinic
- Principal Investigator: Phillip Low, MD, Mayo Clinic
Publications and helpful links
Helpful Links
Study record dates
Study Major Dates
Study Start
Study Start
Primary Completion (Estimated)
Primary Completion
Study Completion (Estimated)
Study Completion
Study Registration Dates
First Submitted
First Submitted
First Submitted That Met QC Criteria
First Submitted That Met QC Criteria
First Posted (Estimated)
First Posted
Study Record Updates
Last Update Posted (Actual)
Last Update Posted
Last Update Submitted That Met QC Criteria
Last Update Submitted That Met QC Criteria
Last Verified
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Synucleinopathies
- Brain Diseases
- Central Nervous System Diseases
- Nervous System Diseases
- Vascular Diseases
- Cardiovascular Diseases
- Pathological Conditions, Anatomical
- Neurodegenerative Diseases
- Movement Disorders
- Basal Ganglia Diseases
- Primary Dysautonomias
- Autonomic Nervous System Diseases
- Hypotension
- Atrophy
- Multiple System Atrophy
- Shy-Drager Syndrome
Other Study ID Numbers
Other Study ID Numbers
- 12-005950
- R01FD004789 (U.S. FDA Grant/Contract)
- R01NS092625 (U.S. NIH Grant/Contract)
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
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