The purpose of this study is to measure outcomes using intranasal and intravenous autologous bone marrow mesenchymal stem cells (BM-MSCs) for Parkinson Disease (PD) and Parkinson's Plus (PPS) patients.
Parkinson Disease (PD) and Parkinson-Plus Syndrome (PPS) are complex neurodegenerative diseases (NDDs) affecting more than 10 million people worldwide. The clinical application of stem cell therapy holds great promise in the treatment of NDDs by promoting regeneration and modulating immune responses with bone marrow aspirate, in particular, holding considerable potential in neural repair and recovery. However, current approaches often rely on university-based laboratories and invasive delivery approaches, raising patient safety, accessibility, and cost concerns. Additionally, NDDs present with distributive and heterogenous pathology, complicating treatment strategies. As pharmaceutical and biotech companies develop targeted stem cell therapies, most focus on localized brain structures rather than targeting PD/PPS systemically. Advancing consensus between scientific research and clinical application is critical for earlier detection in the prodromal phase, identifying epigenetic risk factors, and developing therapeutics that provide a broader, more effective treatment. The primary objective of this study is to measure outcomes using autologus bone marrow mesenchymal stem cells (BM-MSCs) on motor and non-motor function in persons with PD/PPS. The trial will include 60 participants (40 with PD, 20 with PPS) who will complete 7 scheduled encounters (4 in-person visits, 3 remote visits) that occur every 3 months in an alternating manner. There will be 4 treatment groups (2 PD, 2 PPS) who will be administered intranasal bone marrow aspirate and intravenous bone marrow aspirate in a crossover pattern at three of the four in-person visits (Day 0, 6 months and 12 months).
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
SINGLE
Enrollment
60
1. Participant's blood is drawn at the start of each visit. 2. Bone marrow aspirate is drawn from the posterior aspect of the pelvis and is subsequently harvested and processed. 3. The following procedures are administered in a crossover design (Day 0 and 6 months): * Intranasal bone marrow aspirate administration (INA BMAC) OR Sham INA * Intravenous bone marrow aspirate administration (IV BMA) OR Sham IVA 4. At 12 months, all participants receive IV BMA + INA BMAC
Movement-Disorder Society Unified Parkinson Disease Rating Scale (MDS-UPDRS)-III
The MDS-UPDRS is the most widely used clinical rating scale for Parkinson disease. Part III is a motor examination (33 scores summed from 18 questions) conducted by the rater. Total scores can range from 0 to 141, with higher scores indicating worse disease severity.
Time frame: Day 0, 6, 12 and 18 months
10-meter Walk Test (10MWT)
The 10MWT is an assessment of gait speed over a short distance (2 meters ramp up, 6 meters walking, 2 meters ramp down). The aforementioned distances will be pre-measured for accuracy and only the middle 6 meters will be timed. Participants will be asked to walk at a comfortable pace for 2 trials and a fast pace for 2 trials.
Time frame: Day 0, 6, 12 and 18 months
Five Times Sit to Stand (FTSTS)
The FTSTS objectively assesses the time it takes to complete 5 sit-to-stands and is a method to observe movement strategies or compensations. The test will be performed in a standard chair with participants instructed to stand up and sit down 5 times as quickly as possible.
Time frame: Day 0, 6, 12 and 18 months
Mini Balance Evaluation Systems Test (Mini-BESTest)
The Mini-BESTest aims to target 6 different balance control systems. The measure includes 14 items assessing anticipatory postural adjustments, reactive balance control, sensory orientation, and dynamic gait. This is scored on a 3-item ordinal scale resulting in a maximum score of 28.
Time frame: Day 0, 6, 12 and 18 months
The Short Parkinson's Evaluation Scale (SPES)/Scales for Outcomes in Parkinson's Disease - Motor Function (SPES/SCOPA - Motor)
The SPES/Scales for Outcomes in Parkinson's will be used to evaluate motor function and includes 3 sections: Motor evaluation (10 items, maximum of 42 points), Activities of Daily Living (7 items, maximum 21 points), and Motor complications (4 items, maximum 12 points - with 2 items on motor fluctuation \[6 points\] and 2 on dyskinesias \[6 points\]). Response options for all items range 0 to 3.
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Time frame: Day 0, 6, 12 and 18 months
Modified Hoehn & Yahr Scale
The Modified Hoehn and Yahr Scale contains additional criteria to rate Parkinson disease symptoms on a scale of 1-5. Higher scores indicate increased disease progression.
Time frame: Day 0, 6, 12 and 18 months
Montreal Cognitive Assessment (MoCA)
The MoCA is a rapid screen of cognitive abilities to detect mild cognitive dysfunction. Participants are tested on 16 items that cover multiple cognitive domains. The score ranges from 0-30, with higher scores indicating less cognitive impairment.
Time frame: Day 0, 3, 6, 9, 12, 15 and 18 months
Progressive Supranuclear Palsy Clinical Deficits Scale (PSP-CDS)
The PSP-CDS was developed to assess clinical deficits in patients with Progressive Supranuclear Palsy (PSP). The scale measures severity of deficits in seven patient-related clinical domains: Akinesia-rigidity, Bradyphrenia, Communication, Dysphagia, Eye movements, Finger dexterity, and Gait \& balance; each scored from 0 to 3. The sum of the individual domains provides a total score ranging from 0 (no deficit in any domain) to 21 (severe deficit in all domains) with higher scores representing a worse outcome.
Time frame: Day 0, 6, 12 and 18 months
Unified Multiple System Atrophy Rating Scale (UMSARS)
The UMSARS will be used as a clinical rating scale to provide measures of disease progression in multiple systems atrophy. It is composed of four subscales: UMSARS-I (historical review of disease-related impairments, 12 items, scored 0 to 4), UMSARS-II (motor examination, 14 items, scored 0 to 4), UMSARS-III (autonomic examination - records blood pressure and heart rate in the supine and standing positions), and UMSARS-IV (global disability scale - rates chore-based disability, 1 item, ranges from 1 to 5). Higher scores on the UMSARS indicate greater disability.
Time frame: Day 0, 6, 12 and 18 months
Cortical Basal Ganglia Functional Scale (CBFS)
The CBFS is a rating scale that evaluates experiences in daily living (EDLs), behavioral, language, and cognitive impairments in patients with 4 repeat tauopathies (4RTs). The CBFS consists of 14 questions on Motor EDLs and 17 questions on Non-motor EDLs, each of which are rated on a Likert scale rating function from 0 to 4, where 0 = Normal or No problems and 4 = Severe problems. The questions are for the patient, but should be answered by both the patient and their caregiver together.
Time frame: Day 0, 6, 12 and 18 months
Parkinson's Disease Questionnaire - 39 (PDQ-39)
The PDQ-39 is a self report questionnaire that assesses quality of life over the past month across 8 different dimensions (Activities of daily living, Attention and working memory, Cognition, Communication, Depression, Functional mobility, Quality of life, Social relationships, Social relationships, Social support). Items are scored based on a 5-point ordinal system with lower scores reflecting better quality of life. Each dimension total score ranges from 0 (never having difficulty) to 100 (always having difficulty) with lower scores being a better outcome.
Time frame: Day 0, 3, 6, 9, 12, 15 and 18 months
The Scales for Outcomes in Parkinson's disease - Cognition (SCOPA-COG)
The SCOPA-COG consists of 10 items divided over four domains: memory (4 items), attention (2 items), executive function (3 items), and visuospatial function (1 item). Scores range from 0-43, with higher scores reflecting better performance.
Time frame: Day 0, 3, 6, 9, 12, 15 and 18 months
The Scales for Outcomes in Parkinson's Disease - Autonomic Dysfunction
The SCOPA-AUT is self-completed by patients and consists of 23 items assessing the following domains: Gastrointestinal (7 items), Urinary (6 items), Cardiovascular (3 items), Thermoregulatory (4 items), Pupillomotor (1 item), and Sexual (2 items female, 2 items male). The maximum score is 69, with the score for each item ranging from 0 (never experiencing the symptom) to 3 (often experiencing the symptom).
Time frame: Day 0, 3, 6, 9, 12, 15 and 18 months
Non-Motor Symptoms Questionnaire (NMSQ)
The NMSQ is a comprehensive assessment of a diverse range of non-motor symptoms which can occur in all stages of Parkinson's disease. It is a patient-based screening tool designed to draw attention to the presence of non-motor symptoms in patients. Responses are marked as "yes" or "no" in regard to symptoms over the past month.
Time frame: Day 0, 3, 6, 9, 12, 15 and 18 months
MDS Non-Motor Rating Scale (MDS-NMS)
The MDS-NMS is a rater completed assessment that measures frequency and severity of 13 non-motor domains, over 52 items and covers a range of key non-motor symptoms both PD and treatment related. Scores are rated based on symptoms over the past month on frequency (scale from 0 to 4) and severity (scale 0 to 4), with higher scores reflecting more frequent and severe symptoms.
Time frame: Day 0, 3, 6, 9, 12, 15 and 18 months
Resting state brain activation pattern (fMRI analysis)
An anatomical scan using fMRI at the University of Colorado Intermountain Neuroimaging Consortium will performed during a resting state to determine changes in atrophy pattern, volume, cortical thickness, ventricle enlargement, white matter hyperintensities, and magnetic inhomogeneity effects
Time frame: Day 0 and 18 months
Active brain activation pattern (fMRI analysis)
A motor sequencing tapping task and higher order cognitive task (Stroop test) at the University of Colorado Intermountain Neuroimaging Consortium will be performed during the fMRI to determine changes in atrophy pattern, volume, cortical thickness, ventricle enlargement, white matter hyperintensities, and magnetic inhomogeneity effects.
Time frame: Day 0 and 18 months
Active performance accuracy and rate (fMRI analysis)
A motor sequencing tapping task and higher order cognitive task (Stroop test) at the University of Colorado Intermountain Neuroimaging Consortium will be performed during the fMRI to determine changes accuracy and rate of responding for motor performance and cognitive performance.
Time frame: Day 0 and 18 months