Clinical trial NCT06141317: Randomized Clinical Trial in Parkinson's Disease Patients Using Pluripotent Adipose Stem Cells (PASCs)
Official title: Tissue Regeneration and Function Recovery in Patients With Parkinson's Disease Using Allogenic Pluripotent Stem Cells Isolated From Adipose Tissue (PASCs): A Randomized Phase I/IIa Clinical Trial (REPOSE)
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
PHASE2
Conditions: Parkinson Disease
Keywords: Pluripotency
Non-tumorigenic
Neurodegenerative disease
Safety
Efficacy
Tissue/function regeneration
Improve symptoms
Potential cure
Lead sponsor: ClusterXStem-Costa Rica
Sponsor class: OTHER
Collaborators: name: Universidad de Costa Rica
name: University of California, Los Angeles
First posted: 2023-11-21
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to assess the safety and efficacy of allogenic pluripotent stem cells isolated from adipose tissue (PASCs) in patients with Parkinson's Disease.

Detailed description: Pluripotent Adipose-Derived Stem Cells (PASCs) will be delivered intravenously at a dosage of 25 million PASCs/patient to Parkinson's Disease patients for three infusions each spaced 3 months apart (0, 3, and 6 months). Safety and efficacy of PASC treatment will be monitored over 0, 1, 3, 6, and 12 months.

Eligibility criteria: Inclusion Criteria:

1. Men ≥18 years of age or women ≥45 years of age
2. Written informed consent
3. Receiving drug treatment for diagnosis of mild to moderate Parkinson's Disease
4. Modified Hoehn and Yahr stage 1, 2, or 3
5. Diagnosed with Parkinson's Disease for more than 5 years
6. Stable treatment regimen that has not been modified in the 90 days prior to the start of the study
7. No expected addition of symptomatic therapy for at least one year after the start of the study
8. Women of reproductive age must use contraceptive treatment

Exclusion Criteria:

1. Drug-induced Parkinsonism
2. Parkinsonism associated with stroke, progressive supranuclear palsy, Lewy body disease, corticobasal degeneration, or multiple system atrophy
3. Major psychiatric comorbidity that prevents ensuring study follow-up
4. History of alcohol or drug use
5. History of brain surgery for Parkinson's Disease
6. Serious complications deemed inappropriate by Principal Investigator
7. Diagnosis of advanced-stage medical conditions (chronic liver injury with Child-Pugh B or higher, chronic obstructive pulmonary disease with Gold C or higher, or heart failure with ejection fraction \<35%)
8. Use of cytostatic drugs
9. Patients with life expectancy \< 6 months
10. Diabetes mellitus with poor metabolic control (HbA1c \> 8%)
11. Active infectious disease requiring medical treatment
12. Use of systemic steroids or immunosuppressive drugs
13. Patients positive for Hepatitis B antigen, Hepatitis C antibody, or HIV antibody
14. Fertile, pregnant, possibly pregnant, or lactating women
15. History of active mesenchymopathies
16. Active malignancy or diagnosis of malignancy in the last 5 years
17. Abnormal laboratory values, including:

    * AST \>1.5 times Upper Limit of Normal (ULN) (Normal Range: 8 to 48 Units/L)
    * ALT \>1.5 times ULN (Normal Range: 7 to 55 Units/L)
    * Bilirubin \>1.5 times ULN (Normal Range: 0.2 to 1.2 mg/dL)
    * Creatinine \>1.5 times ULN (Normal Range: 0.5 to 1.30 mg/dL)
    * Hematocrit significantly outside normal range (36% to 54%)
    * Lymphocytes significantly outside normal range (103 to 4.8 x 103 lymphocytes/μL)
    * Monocytes significantly outside normal range (200 to 800 lymphocytes/μL)
    * Neutrophils significantly outside normal range (2.5 x 103 to 7 x 103 lymphocytes/μL)
    * Erythrocytes significantly outside normal range (4.7 x 106 to 6.1 x 106 lymphocytes/μL)
    * Platelets significantly outside normal range (150 x 103 to 450 x 103 lymphocytes/μL)

Primary outcomes:
measure: Change in motor function as assessed by the Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Total Score
timeFrame: Day 0, 1 Month, 3 Months, 6 Months, 12 Months
measure: Quality of life as assessed by the 39-item Parkinson's disease Questionnaire (PDQ-39)
timeFrame: Day 0, 1 Month, 3 Months, 6 Months, 12 Months
measure: Speech voice sound and duration
timeFrame: Day 0, 1 Month, 3 Months, 6 Months, 12 Months
measure: Dynamic balance and movement during translational motion and single-limb stance in seconds as assessed by the Mini Balance Evaluation Systems Test (mini BESTest)
timeFrame: Day 0, 1 Month, 3 Months, 6 Months, 12 Months
measure: Balance as assessed by the The Five-times Sit-to-stand Test
timeFrame: Day 0, 1 Month, 3 Months, 6 Months, 12 Months
measure: Mobility and fall risk as assessed by the Timed "Up & Go" test
timeFrame: Day 0, 1 Month, 3 Months, 6 Months, 12 Months
measure: Balance and postural stability as assessed by the Clinical test of Sensory Interaction & Balance Test (CTSIB), stability limits, and unipodal balance test
timeFrame: Day 0, 1 Month, 3 Months, 6 Months, 12 Months
measure: Tremor and handwriting
timeFrame: Day 0, 1 Month, 3 Months, 6 Months, 12 Months
measure: Grip strength
timeFrame: Day 0, 1 Month, 3 Months, 6 Months, 12 Months
measure: Dynamic balance in the bipedal as measured by the 360 degree turn test
timeFrame: Day 0, 1 Month, 3 Months, 6 Months, 12 Months
Secondary outcomes:
measure: Adverse events upon clinical examination
timeFrame: Day 0, 1 Month, 3 Months, 6 Months, 12 Months
measure: Optimal number of doses of 2.5 x 10^7 PASCs for therapeutic response
timeFrame: Day 0, 1 Month, 3 Months, 6 Months, 12 Months
Other outcomes:
Locations:
city: San José
country: Costa Rica
facility: Hospital Clínica Católica
city: San José
country: Costa Rica
facility: Clínica NeuroFT
Study officials:
affiliation: Hospital Clínica Católica
name: Freddy Henriquez, M.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Heneidi S, Simerman AA, Keller E, Singh P, Li X, Dumesic DA, Chazenbalk G. Awakened by cellular stress: isolation and characterization of a novel population of pluripotent stem cells derived from human adipose tissue. PLoS One. 2013 Jun 5;8(6):e64752. doi: 10.1371/journal.pone.0064752. Print 2013.
citation: Gimeno ML, Fuertes F, Barcala Tabarrozzi AE, Attorressi AI, Cucchiani R, Corrales L, Oliveira TC, Sogayar MC, Labriola L, Dewey RA, Perone MJ. Pluripotent Nontumorigenic Adipose Tissue-Derived Muse Cells have Immunomodulatory Capacity Mediated by Transforming Growth Factor-beta1. Stem Cells Transl Med. 2017 Jan;6(1):161-173. doi: 10.5966/sctm.2016-0014. Epub 2016 Aug 2.
citation: Simerman AA, Phan JD, Dumesic DA, Chazenbalk GD. Muse Cells: Nontumorigenic Pluripotent Stem Cells Present in Adult Tissues-A Paradigm Shift in Tissue Regeneration and Evolution. Stem Cells Int. 2016;2016:1463258. doi: 10.1155/2016/1463258. Epub 2016 Dec 14.
citation: Fisch SC, Gimeno ML, Phan JD, Simerman AA, Dumesic DA, Perone MJ, Chazenbalk GD. Pluripotent nontumorigenic multilineage differentiating stress enduring cells (Muse cells): a seven-year retrospective. Stem Cell Res Ther. 2017 Oct 18;8(1):227. doi: 10.1186/s13287-017-0674-3.
citation: Yamashita T, Kushida Y, Abe K, Dezawa M. Non-Tumorigenic Pluripotent Reparative Muse Cells Provide a New Therapeutic Approach for Neurologic Diseases. Cells. 2021 Apr 20;10(4):961. doi: 10.3390/cells10040961.
citation: Leung KL, Chazenbalk GD. Human Pluripotent Nontumorigenic Multilineage Differentiating Stress Enduring (Muse) Cells Isolated from Adipose Tissue: A New Paradigm in Regenerative Medicine and Cell Therapy. In Scientific Principles of Adipose Stem Cells, edited by: L Kokai, K Marra, JP Rubin, Editorial Elsevier, Chapter 6, 91-108, 1st Edition, 2021, https://doi.org/10.1016/B978-0-12-819376-1.00004-4