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

Study Overview
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Brief Summary
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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
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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.

Official Title
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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)

Conditions
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Parkinson Disease

Intervention / Treatment
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* Biological: PASC transplantation (25 million PASCs/patient)
* Biological: Control


Participation Criteria
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Eligibility Criteria
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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)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

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

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in motor function as assessed by the Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Total Score | 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. | Day 0, 1 Month, 3 Months, 6 Months, 12 Months | 
| Quality of life as assessed by the 39-item Parkinson's disease Questionnaire (PDQ-39) | 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. | Day 0, 1 Month, 3 Months, 6 Months, 12 Months | 
| Speech voice sound and duration | 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). | Day 0, 1 Month, 3 Months, 6 Months, 12 Months | 
| Dynamic balance and movement during translational motion and single-limb stance in seconds as assessed by the Mini Balance Evaluation Systems Test (mini BESTest) | 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. | Day 0, 1 Month, 3 Months, 6 Months, 12 Months | 
| Balance as assessed by the The Five-times Sit-to-stand Test | 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. | Day 0, 1 Month, 3 Months, 6 Months, 12 Months | 
| Mobility and fall risk as assessed by the Timed Up & Go test | 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. | Day 0, 1 Month, 3 Months, 6 Months, 12 Months | 
| Balance and postural stability as assessed by the Clinical test of Sensory Interaction & Balance Test (CTSIB), stability limits, and unipodal balance test | 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. | Day 0, 1 Month, 3 Months, 6 Months, 12 Months | 
| Tremor and handwriting | 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. | Day 0, 1 Month, 3 Months, 6 Months, 12 Months | 
| Grip strength | 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. | Day 0, 1 Month, 3 Months, 6 Months, 12 Months | 
| Dynamic balance in the bipedal as measured by the 360 degree turn test | 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. | Day 0, 1 Month, 3 Months, 6 Months, 12 Months | 

Secondary Outcome Measures

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

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Pluripotency, Non-tumorigenic, Neurodegenerative disease, Safety, Efficacy, Tissue/function regeneration, Improve symptoms, Potential cure