Mesenchymal Stem Cell Therapy in Multiple System Atrophy

• Register: ClinicalTrials.gov
• Last refreshed on: 26 September 2023
• Main ID: NCT02315027
• Date of registration: 31/10/2014
• Prospective Registration: No
• Primary sponsor: Mayo Clinic
• Public title: Mesenchymal Stem Cell Therapy in Multiple System Atrophy
• Scientific title: Intrathecal Autologous Mesenchymal Stem Cell Therapy in Multiple System Atrophy (MSA) - Effect of Dose and Natural History
• Date of first enrolment: October 2012
• Target sample size: 30
• Recruitment status: Active, not recruiting
• URL: https://clinicaltrials.gov/ct2/show/NCT02315027
• Study type: Interventional
• Study design: Allocation: Non-Randomized. Intervention model: Sequential Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: Phase 1/Phase 2

Countries of recruitment

United States

Contacts

• Name: Wolfgang Singer, MD
• Affiliation: Mayo Clinic

• Name: Phillip Low, MD
• Affiliation: Mayo Clinic

Key inclusion & exclusion 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



Age minimum: 30 Years
Age maximum: 80 Years
Gender: All

Health Condition(s) or Problem(s) studied

MSA

Intervention(s)

Biological: Autologous Mesenchymal Stem Cells

Primary Outcome(s)

Adverse event frequency (by severity, type, attribution, and intervention dose). [Time Frame: 14 months]

Secondary Outcome(s)

Change in CSF biomarkers from baseline to 2 months. [Time Frame: 2 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]

Rate of change in COMPASS-select score from baseline to 12 months. [Time Frame: 12 months]

Rate of change from baseline to 12 months (or last available date) in UMSARS total score. [Time Frame: 12 months]

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]

Rate of change from baseline to 12 months (or last available date) in UMSARS II score. [Time Frame: 12 months]

Change in CASS score and thermoregulatory sweat test (TST) % from baseline to 12 months. [Time Frame: 12 months]

Secondary ID(s)

R01NS092625

12-005950

R01FD004789

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Secondary Sponsor(s)

National Institute of Neurological Disorders and Stroke (NINDS)

Food and Drug Administration (FDA)