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

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: MSA
• Intervention / Treatment: Biological: Autologous Mesenchymal Stem Cells; Biological: Autologous Mesenchymal Stem Cells; Biological: Autologous Mesenchymal Stem Cells; Biological: Autologous Mesenchymal Stem Cells; Biological: Autologous Mesenchymal Stem Cells

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

Study Locations

• United States
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic in Rochester

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 30 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

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

5

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)	Biological: Autologous Mesenchymal Stem Cells; single dose of 1 × 10(7) cells intrathecally; Biological: Autologous Mesenchymal Stem Cells; 2 doses of 5 × 10(7) cells intrathecally each 1 month (±4 days) apart; Biological: Autologous Mesenchymal Stem Cells; 2 doses of 1 × 10(8) cells intrathecally each 1 month apart; Biological: Autologous Mesenchymal Stem Cells; Ten doses of 5 x 10(7) (±20%) cells intrathecally six months (±1 month) apart; Biological: Autologous Mesenchymal Stem Cells; 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	Biological: Autologous Mesenchymal Stem Cells; single dose of 1 × 10(7) cells intrathecally; Biological: Autologous Mesenchymal Stem Cells; 2 doses of 5 × 10(7) cells intrathecally each 1 month (±4 days) apart; Biological: Autologous Mesenchymal Stem Cells; 2 doses of 1 × 10(8) cells intrathecally each 1 month apart; Biological: Autologous Mesenchymal Stem Cells; Ten doses of 5 x 10(7) (±20%) cells intrathecally six months (±1 month) apart; Biological: Autologous Mesenchymal Stem Cells; 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	Biological: Autologous Mesenchymal Stem Cells; single dose of 1 × 10(7) cells intrathecally; Biological: Autologous Mesenchymal Stem Cells; 2 doses of 5 × 10(7) cells intrathecally each 1 month (±4 days) apart; Biological: Autologous Mesenchymal Stem Cells; 2 doses of 1 × 10(8) cells intrathecally each 1 month apart; Biological: Autologous Mesenchymal Stem Cells; Ten doses of 5 x 10(7) (±20%) cells intrathecally six months (±1 month) apart; Biological: Autologous Mesenchymal Stem Cells; 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.	Biological: Autologous Mesenchymal Stem Cells; single dose of 1 × 10(7) cells intrathecally; Biological: Autologous Mesenchymal Stem Cells; 2 doses of 5 × 10(7) cells intrathecally each 1 month (±4 days) apart; Biological: Autologous Mesenchymal Stem Cells; 2 doses of 1 × 10(8) cells intrathecally each 1 month apart; Biological: Autologous Mesenchymal Stem Cells; Ten doses of 5 x 10(7) (±20%) cells intrathecally six months (±1 month) apart; Biological: Autologous Mesenchymal Stem Cells; 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.	Biological: Autologous Mesenchymal Stem Cells; single dose of 1 × 10(7) cells intrathecally; Biological: Autologous Mesenchymal Stem Cells; 2 doses of 5 × 10(7) cells intrathecally each 1 month (±4 days) apart; Biological: Autologous Mesenchymal Stem Cells; 2 doses of 1 × 10(8) cells intrathecally each 1 month apart; Biological: Autologous Mesenchymal Stem Cells; Ten doses of 5 x 10(7) (±20%) cells intrathecally six months (±1 month) apart; Biological: Autologous Mesenchymal Stem Cells; 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).	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).	12 months
Rate of change from baseline to 12 months (or last available date) in UMSARS II score.	12 months
Rate of change from baseline to 12 months (or last available date) in UMSARS total score.	12 months
Rate of change in COMPASS-select score from baseline to 12 months.	12 months
Change in CASS score and thermoregulatory sweat test (TST) % from baseline to 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.	12 months
Change in CSF biomarkers from baseline to 2 months.	2 months

Collaborators and Investigators

• Sponsor: Mayo Clinic
• Collaborators: National Institute of Neurological Disorders and Stroke (NINDS); Food and Drug Administration (FDA)
• Investigators: Principal Investigator: Wolfgang Singer, MD, Mayo Clinic; Principal Investigator: Phillip Low, MD, Mayo Clinic

Publications and helpful links

General 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.

Helpful Links

• Mayo Clinic Clinical Trials

Study record dates

Study Major Dates

• Study Start: October 1, 2012
• Primary Completion (Estimated): March 1, 2027
• Study Completion (Estimated): March 1, 2027

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): April 8, 2026
• Last Update Submitted That Met QC Criteria: April 2, 2026
• Last Verified: April 1, 2026

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: 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