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

Phase 1

Active, not recruiting

• Conditions: Parkinson Disease
• Interventions: Biological: PASC transplantation (25 million PASCs/patient); Biological: Control

• Registration Number: NCT06141317
• Lead Sponsor: ClusterXStem-Costa Rica

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.

Study Timeline

• Study Start: 2023-06-23
• Status Verified: 2023-11
• Study First Submitted: 2023-11-15
• Study First Submitted QC: 2023-11-15
• Study First Posted: 2023-11-21
• Last Update Submitted: 2023-11-28
• Last Update Posted: 2023-12-01
• Primary Completion: 2024-09-01
• Study Completion: 2024-11-01

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 40

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)

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
PASC transplantation (25 million PASCs/patient)	PASC transplantation (25 million PASCs/patient)	Pluripotent Adipose-Derived Stem Cells will be delivered intravenously
Control	Control	Saline solution will be delivered intravenously

Primary Outcome Measures

Name	Time	Method
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.
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.
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.
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.
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.
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.
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.

Secondary Outcome Measures

Name	Time	Method
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.
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.

Trial Locations

Locations (2)

Hospital Clínica Católica; 🇨🇷 San José, Costa Rica

Clínica NeuroFT; 🇨🇷 San José, Costa Rica