Clinical trial NCT04876326: Potential Use of Autologous and Allogeneic Mesenchymal Stem Cells in Patients With Multiple System Atrophy
Official title: Potential Use of Autologous and Allogeneic Mesenchymal Stem Cells in Patients With Multiple System Atrophy
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Multiple System Atrophy
Parkinsonism
Multiple System Atrophy, Parkinson Variant
Keywords: Multiple System Atrophy, Parkinson Variant
Mesenchymal Stem Cell
Parkinsonism
UMSARS
MRI
FGD-PET SCAN
DaTScan
SSR, RR-Interval
Composite Autonomic Severity Score
ILG-1, BDNF
ERG (Electroretinogram)
VEP (Visual Evoked Potential)
HD-OCT (High Definition-optical coherence tomography)
Lead sponsor: Indonesia University
Sponsor class: OTHER
First posted: 2021-05-06
Enrollment: 15
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The prevalence of Multiple System Atrophy (MSA) is reported to be between 3.4 - 4.9 cases per 100,000 population. The estimated average incidence is 0.6 - 0.7 cases per 100,000 people per year. Many patients are not diagnosed properly during their lifetime because of the difficulty in differentiating MSA from other disorders. Approximately 29 - 33% of patients with isolated late onset cerebellar ataxia and 8 - 10% of patients with parkinsonism will develop MSA.

There are currently no therapies that can cure or stop the progression of the disease. The current pharmacological therapy is only to relieve symptoms. Mesenchymal stem cells (MSC) are considered an efficient source of cells for therapy, because they can be safely harvested and transplanted to donors or patients, have low immunogenicity, and have broad therapeutic potential. Results from preliminary preclinical and clinical trials indicate the potential of MSC-based treatment in meeting several key aspects of neurodegeneration. Stem cell-based therapy for neurodegenerative diseases aims to stop clinical damage by regenerating and by providing local support for damaged tissue, in addition after transplantation, MSCs have been shown to be capable of penetrating the lesion area and thus have great potential use as a means of administering therapeutic agents.

The subjects of this study were patients who experienced possible MSA based on the consensus clinical criteria for MSA. There will be three treatment groups with a total sample of 5 subjects each.

Group 1 will receives MSC-Adipose Autologous with doses 2x50 million cells intratechally.

Group 2 will receives MSC-Umbilical Cord Allogeneic with doses 2x 50 million cells intratechally.

Group 3 will receives MSC-Umbilical Cord Allogeneic with doses 2x50 million cells intratechally and 2x10cc secretome MSC from Adipose Intravenously.

Clinical improvement will be evaluated using the UMSARS scale, PET-Scans, MRI, DaTScan, IGF-1, BDNF, Sympathetic skin respons (SSR), EMG, Composite Autonomic Severity Score (CASS), High definition-Optical coherence tomography (HD-OCT), ERG, VEP, Log MAR chart, Ishihara test and side adverse effect on MSC.

This study is divided into six timeframes : Before an implantation, First Month after second implantation, Third month after secondary implantation, Sixth month after second implantation, Ninth month after second implantation and Twelve month after second implantation. The differences between the test variables are then used as an indicator to assess clinical improvement within the subjects.


Eligibility criteria: Inclusion Criteria:

* Patients developed MSA based on clinical examination and consensus MSA criteria.
* Patients diagnosed with MSA for less than 4 years.
* Patients with an anticipated survival of at least 3 years in the opinion of the examiner.
* Patients with MOCa and Mini Mental State Examination (MMSE) values of more than 24.
* For Adipose Autologous-MSC group subjects were not experiencing active infection, which was confirmed by screening for HbSAg, Anti HCV, Syphilis, HIV, CMV, Rubella, and Toxoplasma.
* Subjects are willing to participate in research and fill out an informed consent form.
* Do not have autoimmune disorder, or undergoes management disorders and / or other diseases related to MSA
* Subjects are willing to participate in research and fill out an informed consent form.

Exclusion Criteria:

* Suffer from systemic autoimmune diseases (systemetic lupus erythomatosus, Addison's disease, Crohn's disease, arthritis management), immunodeficiency (SIDA), or blood clotting disorders or management of malignant diseases (diseases associated with MSA)
* Undergo immunosuppressive therapy, anticoagulants or corticosteroids.
* Patients with malignant neoplasms and close family history of neoplasms.
* already had history of spinal surgery, have paralysis or have spinal diseases.
* Patients with a history of electroconvulsive therapy.
* Patients with a history of brain surgery for Parkinson's disease.
* Patients with systemic or local infections located close to the injection site.
* Undergo immunosuppressive therapy, anticoagulants or corticosteroids.
* The patient was not willing to take part in the study and did not fill out informed consent.

Primary outcomes:
measure: Changes of Clinical Evaluation from Baseline to 1,3,6,9 and 12 months after second implantation
timeFrame: Pre-implantation, 1st Month, 3rd Months, 6th Months , 9th, 12th Months After Second Implantation
measure: Changes of Clinical Evaluation from Baseline to 1,3,6,9 and 12 months after second implantation
timeFrame: Pre-implantation, 1st Month, 3rd Months, 6th Months , 9th, 12th Months After Second Implantation
measure: Changes of structures improvement of the eyes from Baseline to 1,3,6,9 and 12 months after second implantation
timeFrame: Pre-implantation, 1st Month, 3rd Months, 6th Months , 9th, 12th Months After Second Implantation
measure: Changes of structures improvement of the eyes from Baseline to 1,3,6,9 and 12 months after second implantation
timeFrame: Pre-implantation, 1st Month, 3rd Months, 6th Months , 9th, 12th Months After Second Implantation
measure: Changes of the eyesight from Baseline to 1,3,6,9 and 12 months after second implantation
timeFrame: Pre-implantation, 1st Month, 3rd Months, 6th Months , 9th, 12th Months After Second Implantation
measure: Changes of the eyesight from Baseline to 1,3,6,9 and 12 months after second implantation
timeFrame: Pre-implantation, 1st Month, 3rd Months, 6th Months , 9th, 12th Months After Second Implantation
measure: Changes of the eyesight from Baseline to 1,3,6,9 and 12 months after second implantation
timeFrame: Pre-implantation, 1st Month, 3rd Months, 6th Months , 9th, 12th Months After Second Implantation
measure: Changes of the eyesight from Baseline to 1,3,6,9 and 12 months after second implantation
timeFrame: Pre-implantation, 1st Month, 3rd Months, 6th Months , 9th, 12th Months After Second Implantation
measure: Imaging Evaluation from Baseline to 1,3,6,9 and 12 months after second implantation
timeFrame: Pre-implantation, 1st Month, 3rd Months, 6th Months , 9th, 12th Months After Second Implantation
measure: Imaging Evaluation from Baseline to 1,3,6,9 and 12 months after second implantation
timeFrame: Pre-implantation, 1st Month, 3rd Months, 6th Months , 9th, 12th Months After Second Implantation
measure: Imaging Evaluation from Baseline to 1,3,6,9 and 12 months after second implantation
timeFrame: Pre-implantation, 1st Month, 3rd Months, 6th Months , 9th, 12th Months After Second Implantation
Secondary outcomes:
Other outcomes:
Locations:
city: Jakarta Pusat
country: Indonesia
facility: Cipto Mangunkusumo General Hospital
state: DKI Jakarta
Study officials:
References: