Mesenchymal Stem Cell Therapy in Multiple System Atrophy

NCT ID: NCT02315027

Last Updated: 2025-04-03

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 30 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-10-31
• Study Completion Date: 2026-03-31

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.

Conditions

MSA

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

1 dose of 1 × 10(7) MSCs

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

Group Type: EXPERIMENTAL

Autologous Mesenchymal Stem Cells

Intervention Type: BIOLOGICAL

single dose of 1 × 10(7) cells intrathecally

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

Group Type: EXPERIMENTAL

Autologous Mesenchymal Stem Cells

Intervention Type: BIOLOGICAL

2 doses of 5 × 10(7) cells intrathecally each 1 month (±4 days) apart

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

Group Type: EXPERIMENTAL

Autologous Mesenchymal Stem Cells

Intervention Type: BIOLOGICAL

2 doses of 1 × 10(8) cells intrathecally each 1 month apart

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.

Group Type: EXPERIMENTAL

Autologous Mesenchymal Stem Cells

Intervention Type: BIOLOGICAL

Ten doses of 5 x 10(7) (±20%) cells intrathecally six months (±1 month) apart

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.

Group Type: EXPERIMENTAL

Autologous Mesenchymal Stem Cells

Intervention Type: BIOLOGICAL

Ten doses of 2.5 x 10(7) (±20%) cells intrathecally six months (±1 month) apart

Interventions

Autologous Mesenchymal Stem Cells

single dose of 1 × 10(7) cells intrathecally

Intervention Type: BIOLOGICAL

Autologous Mesenchymal Stem Cells

2 doses of 5 × 10(7) cells intrathecally each 1 month (±4 days) apart

Intervention Type: BIOLOGICAL

Autologous Mesenchymal Stem Cells

2 doses of 1 × 10(8) cells intrathecally each 1 month apart

Intervention Type: BIOLOGICAL

Autologous Mesenchymal Stem Cells

Ten doses of 5 x 10(7) (±20%) cells intrathecally six months (±1 month) apart

Intervention Type: BIOLOGICAL

Autologous Mesenchymal Stem Cells

Ten doses of 2.5 x 10(7) (±20%) cells intrathecally six months (±1 month) apart

Intervention Type: BIOLOGICAL

Eligibility Criteria

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

• Minimum Eligible Age: 30 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Food and Drug Administration (FDA)

FED

Sponsor Role: collaborator

National Institute of Neurological Disorders and Stroke (NINDS)

NIH

Sponsor Role: collaborator

Mayo Clinic

OTHER

Sponsor Role: lead

Responsible Party

Wolfgang Singer, MD

Associate Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Wolfgang Singer, MD

Role: PRINCIPAL_INVESTIGATOR

Mayo Clinic

Phillip Low, MD

Role: PRINCIPAL_INVESTIGATOR

Mayo Clinic

Locations

Mayo Clinic in Rochester

Rochester, Minnesota, United States

Countries

United States

References

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.

Reference Type: DERIVED

PMID: 27515308 (View on PubMed)

Other Identifiers

R01FD004789

Identifier Type: FDA

Identifier Source: secondary_id

View Link

R01NS092625

Identifier Type: NIH

Identifier Source: secondary_id

View Link

12-005950

Identifier Type: -

Identifier Source: org_study_id