Randomized Clinical Trial in Parkinson's Disease Patients Using Pluripotent Adipose Stem Cells (PASCs)

Sponsor

ClusterXStem-Costa Rica (Other)

Overall Status

Active, not recruiting

CT.gov ID

NCT06141317

Collaborator

Universidad de Costa Rica (Other), University of California, Los Angeles (Other)

Enrollment

Locations

Arms

16.3

Anticipated Duration (Months)

Patients Per Site

1.2

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Parkinson Disease	Biological: PASC transplantation (25 million PASCs/patient) Biological: Control	Phase 1/Phase 2

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

40 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

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)

Actual Study Start Date :

Jun 23, 2023

Anticipated Primary Completion Date :

Sep 1, 2024

Anticipated Study Completion Date :

Nov 1, 2024

Arms and Interventions

Arm	Intervention/Treatment
Experimental: PASC transplantation (25 million PASCs/patient) Pluripotent Adipose-Derived Stem Cells will be delivered intravenously	Biological: PASC transplantation (25 million PASCs/patient) 3 doses of 25 million PASCs implantation via peripheral vein (Day 0, 3 months, 6 months)
Placebo Comparator: Control Saline solution will be delivered intravenously	Biological: Control 0.9% saline solution via peripheral vein (Day 0, 3 months, 6 months)

Arm

Intervention/Treatment

Experimental: PASC transplantation (25 million PASCs/patient)

Pluripotent Adipose-Derived Stem Cells will be delivered intravenously

Biological: PASC transplantation (25 million PASCs/patient)

3 doses of 25 million PASCs implantation via peripheral vein (Day 0, 3 months, 6 months)

Placebo Comparator: Control

Saline solution will be delivered intravenously

Biological: Control

0.9% saline solution via peripheral vein (Day 0, 3 months, 6 months)

Outcome Measures

Primary Outcome Measures

Change in motor function as assessed by the Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Total Score [Day 0, 1 Month, 3 Months, 6 Months, 12 Months]
The MDS-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) is a widely used research tool to quantify the clinical characteristics of PD in adults. This scale assesses various aspects of Parkinson's disease, including motor and non-motor experiences of daily life and motor complications. This test will take approximately 30 minutes, assessing the impact of the disease in 4 different domains distributed in 65 items, of which 48 are scored from 0 to 4 and seven with dichotomous answers of "yes" or "no". The global range of the MDS-UPDRS will be from 0 to 260 points, the higher the score, the greater the disease involvement.
Quality of life as assessed by the 39-item Parkinson's disease Questionnaire (PDQ-39) [Day 0, 1 Month, 3 Months, 6 Months, 12 Months]
The 39-item Parkinson's disease Questionnaire (PDQ-39) is the most widely test used to assess specific quality of life questionnaire for Parkinson's disease, and it has been validated and cross-culturally translated. The questionnaire consists of 39 questions to be completed by the patient, that assesses the frequency in which patients with PD experience difficulties in 8 dimensions of functionality and well-being: mobility, activities of daily living, emotional well- being, attention and memory, social support, depression, cognition, communication and social relationships. Items can be transformed on a linear scale from 0 to 100, the higher the score reflects a lower quality of life.
Speech voice sound and duration [Day 0, 1 Month, 3 Months, 6 Months, 12 Months]
Since most people with Parkinson's disease (PD) have voice and speech disorders that result in harmful effects on communication and quality of life; the measurement of the pressure level and sound duration will be executed using the Samson Go Mic and the software used for the Lee Silverman Voice Treatment Therapy (LSVT LOUD).
Dynamic balance and movement during translational motion and single-limb stance in seconds as assessed by the Mini Balance Evaluation Systems Test (mini BESTest) [Day 0, 1 Month, 3 Months, 6 Months, 12 Months]
The Mini Balance Evaluation Systems Test (mini BESTest) has proven to be a reliable and valid measurement tool for patients with PD. It is aimed to measure dynamic balance and associated movement during translational motion. The test consists of 14 items, with a maximum score of 28 points, with a higher test result, the greater the patient's functionality 35 . The test has high inter-rater reliability (ICC = 0.92) and high test-retest reliability (ICC = 0.92) for PD patients.
Balance as assessed by the The Five-times Sit-to-stand Test [Day 0, 1 Month, 3 Months, 6 Months, 12 Months]
The Five-times sit-to-stand Test is a tool that quantifies the ability of patients suffering from diseases associated with balance problems, as in the case of PD, to perform transitional motions. In addition, it has been used as a measure of lower limb strength. The test has excellent inter-rater reliability and high test-retest reliability, as well as assessing for the risk of falls in patients with PD.
Mobility and fall risk as assessed by the Timed "Up & Go" test [Day 0, 1 Month, 3 Months, 6 Months, 12 Months]
The Timed "Up & Go" test consists of observing and timing the patient as he gets up from an armchair, walking for 3 meters, turns, returns and sits down again. The results of this test correlates well with the logarithmic transformation scores on the Berg Balance Scale, gait speed and the Barthel Index of AVD (Activities of Daily Living), and can predict the patient's ability to walk alone safely.
Balance and postural stability as assessed by the Clinical test of Sensory Interaction & Balance Test (CTSIB), stability limits, and unipodal balance test [Day 0, 1 Month, 3 Months, 6 Months, 12 Months]
Computerized posturography using a force platform system provides objective and quantitative evaluations of deficiencies in postural control. The participants of the present study will be subjected to two tests of balance and postural stability using the HUMAC®43 brand force platform system. Three tests will be performed: CTSIB test (Clinical test of Sensory Interaction & Balance), the stability limits, and the unipodal balance test.
Tremor and handwriting [Day 0, 1 Month, 3 Months, 6 Months, 12 Months]
Alterations in the kinematics of handwriting are among the recently proposed biomarkers of PD. Recent studies have suggested the potential of handwriting analysis for both early diagnosis and assessment of disease progression. In the present study, the patients will be subjected to 5 tests, at 5 different times of the study using the MovAlyzeR® software in conjunction with the WACOM ONE tablet, to measure the speed, amplitude, fluidity and tremor of the movements of the upper extremities.
Grip strength [Day 0, 1 Month, 3 Months, 6 Months, 12 Months]
The decrease in grip strength is a predictor of adverse outcomes in older adults and will be determined using a Jamar brand digital dynamometer to measure the grip strength of the patients participating in each assessment.
Dynamic balance in the bipedal as measured by the 360 degree turn test [Day 0, 1 Month, 3 Months, 6 Months, 12 Months]
This test measures dynamic balance in the bipedal. In this test, the number of steps and the time that take the patient to make a complete 360-degree turn will be measured.

Secondary Outcome Measures

Adverse events upon clinical examination [Day 0, 1 Month, 3 Months, 6 Months, 12 Months]
Study participants will be examined for clinical signs of adverse events.
Optimal number of doses of 2.5 x 10^7 PASCs for therapeutic response [Day 0, 1 Month, 3 Months, 6 Months, 12 Months]
The optimal number of doses of PASCs for therapeutic response will be measured.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 80 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

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

Exclusion Criteria:

Drug-induced Parkinsonism
Parkinsonism associated with stroke, progressive supranuclear palsy, Lewy body disease, corticobasal degeneration, or multiple system atrophy
Major psychiatric comorbidity that prevents ensuring study follow-up
History of alcohol or drug use
History of brain surgery for Parkinson's Disease
Serious complications deemed inappropriate by Principal Investigator
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%)
Use of cytostatic drugs
Patients with life expectancy < 6 months
Diabetes mellitus with poor metabolic control (HbA1c > 8%)
Active infectious disease requiring medical treatment
Use of systemic steroids or immunosuppressive drugs
Patients positive for Hepatitis B antigen, Hepatitis C antibody, or HIV antibody
Fertile, pregnant, possibly pregnant, or lactating women
History of active mesenchymopathies
Active malignancy or diagnosis of malignancy in the last 5 years
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)