- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02315027
Mesenchymal Stem Cell Therapy in Multiple System Atrophy
September 13, 2023 updated by: Wolfgang Singer, MD, Mayo Clinic
Intrathecal Autologous Mesenchymal Stem Cell Therapy in Multiple System Atrophy (MSA) - Effect of Dose and Natural History
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.
Study Overview
Status
Active, not recruiting
Conditions
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
Interventional
Enrollment (Actual)
30
Phase
- Phase 2
- Phase 1
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
-
-
Minnesota
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Rochester, Minnesota, United States, 55905
- Mayo Clinic in Rochester
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-
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
30 years to 80 years (Adult, Older Adult)
Accepts Healthy Volunteers
No
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
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Non-Randomized
- Interventional Model: Sequential Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / 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
Outcome Measure |
Time Frame |
---|---|
Adverse event frequency (by severity, type, attribution, and intervention dose).
Time Frame: 14 months
|
14 months
|
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
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2 months
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Collaborators
Investigators
- Principal Investigator: Wolfgang Singer, MD, Mayo Clinic
- Principal Investigator: Phillip Low, MD, Mayo Clinic
Publications and helpful links
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
Helpful Links
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start
October 1, 2012
Primary Completion (Estimated)
March 1, 2024
Study Completion (Estimated)
March 1, 2024
Study Registration Dates
First Submitted
October 31, 2014
First Submitted That Met QC Criteria
December 9, 2014
First Posted (Estimated)
December 11, 2014
Study Record Updates
Last Update Posted (Actual)
September 14, 2023
Last Update Submitted That Met QC Criteria
September 13, 2023
Last Verified
September 1, 2023
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Cardiovascular Diseases
- Vascular Diseases
- Brain Diseases
- Central Nervous System Diseases
- Nervous System Diseases
- Basal Ganglia Diseases
- Movement Disorders
- Synucleinopathies
- Neurodegenerative Diseases
- Pathological Conditions, Anatomical
- Autonomic Nervous System Diseases
- Primary Dysautonomias
- Hypotension
- Atrophy
- Multiple System Atrophy
- Shy-Drager Syndrome
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
Yes
Studies a U.S. FDA-regulated device product
No
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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