The purpose of this study is to assess the safety, feasibility, and efficacy of intravenous allogeneic bone marrow-derived mesenchymal stem cell (MSC) therapy for idiopathic Parkinson's disease (iPD).
Allogeneic bone marrow-derived mesenchymal stem cells (MSCs) will be delivered intravenously at one of four doses: 1 x 10 6 MSC/kg, 3 x 10 6 MSC/kg, 6 x 10 6 MSC/kg, or 10 x 10 6 MSC/kg of body weight to a population of patients with idiopathic Parkinson's disease (iPD). The infusion will be at 1 week after the baseline visit, following two screening visits. Patients will be followed until 52 weeks after the infusion visit. The safety of the therapy, as well as the impact of the therapy on the rate of Parkinson's disease (PD) progression, will be assessed.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
20
Bone marrow-derived allogeneic MSCs will be delivered intravenously in escalating doses of 1 x 10 6 MSC/kg, 3 x 10 6 MSC/kg, 6 x 10 6 MSC/kg, or 10 x 10 6 MSC/kg of body weight to a population of patients with idiopathic Parkinson's disease (iPD).
Bone marrow-derived allogeneic MSCs will be delivered intravenously in escalating doses of 1 x 10 6 MSC/kg, 3 x 10 6 MSC/kg, 6 x 10 6 MSC/kg, or 10 x 10 6 MSC/kg of body weight to a population of patients with idiopathic Parkinson's disease (iPD).
The University of Texas Health Science Center at Houston
Houston, Texas, United States
Safety of allogeneic MSC therapy in patients with iPD as indicated by the presence of adverse events that are confirmed to be related to the therapy
Adverse events include renal failure, liver failure, and hemolytic anemia.
Time frame: 3 weeks after the first infusion
Safety of allogeneic MSC therapy in patients with iPD as indicated by the presence of adverse events that are confirmed to be related to the therapy
Adverse events include renal failure, liver failure, and hemolytic anemia.
Time frame: 12 weeks after the first infusion
Safety of allogeneic MSC therapy in patients with iPD as indicated by the presence of adverse events that are confirmed to be related to the therapy
Adverse events include renal failure, liver failure, and hemolytic anemia.
Time frame: 24 weeks after the first infusion
Safety of allogeneic MSC therapy in patients with iPD as indicated by the presence of adverse events that are confirmed to be related to the therapy
Adverse events include renal failure, liver failure, and hemolytic anemia.
Time frame: 52 weeks after the first infusion
Change in motor function as assessed by the Unified Parkinson's Disease Rating Scale (UPDRS) Total score
The UPDRS serves as a disability and impairment scale for progression follow-up and is divided into four sections. * Part I: evaluation of mentation, behavior, and mood (13 questions). * Part II: evaluation of activities of daily living including speech, swallowing, handwriting, dressing, hygiene, falling, salivating, turning in bed, walking, and cutting food (13 questions). * Part III: motor examination (33 scores based on 18 questions with right, left or other body distributions scores) * Part IV: motor complications (6 questions) All items have 5 response options with uniform anchors of: 0 = normal, 1 = slight (symptoms/signs with sufficiently low frequency or intensity to cause no impact on function), 2 = mild (symptoms/signs of frequency or intensity sufficient to cause a modest impact on function, 3 = moderate (symptoms/signs sufficiently frequent or intense to impact considerably, but not prevent function), 4 = severe (symptoms/signs that prevent function).
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Bone marrow-derived allogeneic MSCs will be delivered intravenously in escalating doses of 1 x 10 6 MSC/kg, 3 x 10 6 MSC/kg, 6 x 10 6 MSC/kg, or 10 x 10 6 MSC/kg of body weight to a population of patients with idiopathic Parkinson's disease (iPD).
Bone marrow-derived allogeneic MSCs will be delivered intravenously in escalating doses of 1 x 10 6 MSC/kg, 3 x 10 6 MSC/kg, 6 x 10 6 MSC/kg, or 10 x 10 6 MSC/kg of body weight to a population of patients with idiopathic Parkinson's disease (iPD).
Time frame: baseline, 3 weeks
Change in motor function as assessed by the Unified Parkinson's Disease Rating Scale (UPDRS) Total score
The UPDRS serves as a disability and impairment scale for progression follow-up and is divided into four sections. * Part I: evaluation of mentation, behavior, and mood (13 questions). * Part II: evaluation of activities of daily living including speech, swallowing, handwriting, dressing, hygiene, falling, salivating, turning in bed, walking, and cutting food (13 questions). * Part III: motor examination (33 scores based on 18 questions with right, left or other body distributions scores) * Part IV: motor complications (6 questions) All items have 5 response options with uniform anchors of: 0 = normal, 1 = slight (symptoms/signs with sufficiently low frequency or intensity to cause no impact on function), 2 = mild (symptoms/signs of frequency or intensity sufficient to cause a modest impact on function, 3 = moderate (symptoms/signs sufficiently frequent or intense to impact considerably, but not prevent function), 4 = severe (symptoms/signs that prevent function).
Time frame: baseline, 12 weeks
Change in motor function as assessed by the Unified Parkinson's Disease Rating Scale (UPDRS) Total score
The UPDRS serves as a disability and impairment scale for progression follow-up and is divided into four sections. * Part I: evaluation of mentation, behavior, and mood (13 questions). * Part II: evaluation of activities of daily living including speech, swallowing, handwriting, dressing, hygiene, falling, salivating, turning in bed, walking, and cutting food (13 questions). * Part III: motor examination (33 scores based on 18 questions with right, left or other body distributions scores) * Part IV: motor complications (6 questions) All items have 5 response options with uniform anchors of: 0 = normal, 1 = slight (symptoms/signs with sufficiently low frequency or intensity to cause no impact on function), 2 = mild (symptoms/signs of frequency or intensity sufficient to cause a modest impact on function, 3 = moderate (symptoms/signs sufficiently frequent or intense to impact considerably, but not prevent function), 4 = severe (symptoms/signs that prevent function).
Time frame: baseline, 24 weeks
Change in motor function as assessed by the Unified Parkinson's Disease Rating Scale (UPDRS) Total score
The UPDRS serves as a disability and impairment scale for progression follow-up and is divided into four sections. * Part I: evaluation of mentation, behavior, and mood (13 questions). * Part II: evaluation of activities of daily living including speech, swallowing, handwriting, dressing, hygiene, falling, salivating, turning in bed, walking, and cutting food (13 questions). * Part III: motor examination (33 scores based on 18 questions with right, left or other body distributions scores) * Part IV: motor complications (6 questions) All items have 5 response options with uniform anchors of: 0 = normal, 1 = slight (symptoms/signs with sufficiently low frequency or intensity to cause no impact on function), 2 = mild (symptoms/signs of frequency or intensity sufficient to cause a modest impact on function, 3 = moderate (symptoms/signs sufficiently frequent or intense to impact considerably, but not prevent function), 4 = severe (symptoms/signs that prevent function).
Time frame: baseline, 52 weeks
Change in motor function as assessed by the UPDRS Motor score
Parts III and IV of the UPDRS will be performed as described above.
Time frame: baseline, 3 weeks
Change in motor function as assessed by the UPDRS Motor score
Parts III and IV of the UPDRS will be performed as described above.
Time frame: baseline, 12 weeks
Change in motor function as assessed by the UPDRS Motor score
Parts III and IV of the UPDRS will be performed as described above.
Time frame: baseline, 24 weeks
Change in motor function as assessed by the UPDRS Motor score
Parts III and IV of the UPDRS will be performed as described above.
Time frame: baseline, 52 weeks
Change in motor function as assessed by Timed-Up-and-Go (TUG)
Time in seconds required to stand from a chair, walk 7meters, turn, walk back to the chair and sit down.
Time frame: baseline, 3 weeks
Change in motor function as assessed by Timed-Up-and-Go (TUG)
Time in seconds required to stand from a chair, walk 7meters, turn, walk back to the chair and sit down.
Time frame: baseline, 12 weeks
Change in motor function as assessed by Timed-Up-and-Go (TUG)
Time in seconds required to stand from a chair, walk 7meters, turn, walk back to the chair and sit down.
Time frame: baseline, 24 weeks
Change in motor function as assessed by Timed-Up-and-Go (TUG)
Time in seconds required to stand from a chair, walk 7meters, turn, walk back to the chair and sit down.
Time frame: baseline, 52 weeks
Change in disability as measured by the Modified Hoehn and Yahr Scale
The Modified Hoehn and Yahr Scale is a staging instrument that defines broad categories of motor function in Parkinson's disease, starting at Stage 0: no signs of disease to the highest stage 5: wheelchair bound or bedridden unless aided.
Time frame: baseline, 3 weeks
Change in disability as measured by the Modified Hoehn and Yahr Scale
The Modified Hoehn and Yahr Scale is a staging instrument that defines broad categories of motor function in Parkinson's disease, starting at Stage 0: no signs of disease to the highest stage 5: wheelchair bound or bedridden unless aided.
Time frame: baseline, 12 weeks
Change in disability as measured by the Modified Hoehn and Yahr Scale
The Modified Hoehn and Yahr Scale is a staging instrument that defines broad categories of motor function in Parkinson's disease, starting at Stage 0: no signs of disease to the highest stage 5: wheelchair bound or bedridden unless aided.
Time frame: baseline, 24 weeks
Change in disability as measured by the Modified Hoehn and Yahr Scale
The Modified Hoehn and Yahr Scale is a staging instrument that defines broad categories of motor function in Parkinson's disease, starting at Stage 0: no signs of disease to the highest stage 5: wheelchair bound or bedridden unless aided.
Time frame: baseline, 52 weeks
functional connectivity between substantia nigra and dorsal striatum as assessed by resting state functional magnetic resonance imaging (fMRI)
Diffusion tensor and T2 imaging with the resting state functional connectivity technique will be used.
Time frame: baseline
perfusion as assessed by arterial spin-labeled (ASL) perfusion MRI
Resting cerebral blood flow (CBF) will be measured using a pseudo-continuous arterial spin labeling (pCASL) MRI sequence with gradient-echo echo-planar imaging (EPI), which allows for a non-invasive quantification of CBF.
Time frame: baseline
structural connectivity as assessed by diffusion-weighted MRI for diffusion tensor image (DTI) analysis
A set of diffusion-weighted image volumes (32-directions, high angular resolution) will be collected using the gradient overplus option with one B0 (non-diffusion weighted) image volume acquired before the acquisition of one repetition of the diffusion-weighted scans. Diffusion tensor and associated computations will be performed. White matter microstructure will be examined, which represents the structural pathways linking specific cortical and subcortical regions. It will be determined whether there is increased fractional anisotropy and decreased mean diffusivity along white matter fibers that link regions exhibiting increased functional connectivity, such as substantia nigra and dorsal striatum.
Time frame: baseline
volume of subcortical structures as assessed by T1- and T2- weighted MRI with Fluid Attenuated Inversion Recovery
Anatomical imaging allows visualization of the brain structure at the level of about 1 cubic millimeter. These scans will be used to estimate the volume of subcortical structures (e.g., putamen, caudate nucleus).
Time frame: baseline
cortical thickness as assessed by T1- and T2- weighted MRI with Fluid Attenuated Inversion Recovery
Anatomical imaging allows visualization of the brain structure at the level of about 1 cubic millimeter. These scans will be used to measure cortical thickness (e.g., gray matter density).
Time frame: baseline
Change in gross brain structure as assessed by T1- and T2- weighted MRI with Fluid Attenuated Inversion Recovery
Anatomical imaging allows visualization of the brain structure at the level of about 1 cubic millimeter. These scans will be used to detect any gross structural changes or inflammation that appear during the course of treatment.
Time frame: baseline
Change in brain activity as assessed by task state fMRI
Whole-brain echo-planar imaging (EPI) runs sensitive to BOLD contrast will be acquired while participants do self-paced finger tapping using their left and right hands at separate points in time, and during the resting state after being instructed to remain still and fixate on a white crosshair displayed on a black background during the functional acquisition. Functional imaging will be done in the OFF medication state. It will be determined whether there is a reduction in the abnormally high activity pattern in motor cortex and an increase in putamen activity.
Time frame: baseline
Change in quality of life as assessed by the modified Schwab and England activities of daily living (ADL) score
The Schwab \& England scale is a physician assessment of the subject's level of independence. The subject will be scored on a percentage scale reflective of his/her ability to perform acts of daily living in relation to what he/she did before Parkinson disease appeared. Scores range from 100% to 0% in increments of 10%, where 100% is completely independent and 0% is only vegetative functions.
Time frame: baseline, 3 weeks
Change in quality of life as assessed by the modified Schwab and England activities of daily living (ADL) score
The Schwab \& England scale is a physician assessment of the subject's level of independence. The subject will be scored on a percentage scale reflective of his/her ability to perform acts of daily living in relation to what he/she did before Parkinson disease appeared. Scores range from 100% to 0% in increments of 10%, where 100% is completely independent and 0% is only vegetative functions.
Time frame: baseline, 12 weeks
Change in quality of life as assessed by the modified Schwab and England activities of daily living (ADL) score
The Schwab \& England scale is a physician assessment of the subject's level of independence. The subject will be scored on a percentage scale reflective of his/her ability to perform acts of daily living in relation to what he/she did before Parkinson disease appeared. Scores range from 100% to 0% in increments of 10%, where 100% is completely independent and 0% is only vegetative functions.
Time frame: baseline, 24 weeks
Change in quality of life as assessed by the modified Schwab and England activities of daily living (ADL) score
The Schwab \& England scale is a physician assessment of the subject's level of independence. The subject will be scored on a percentage scale reflective of his/her ability to perform acts of daily living in relation to what he/she did before Parkinson disease appeared. Scores range from 100% to 0% in increments of 10%, where 100% is completely independent and 0% is only vegetative functions.
Time frame: baseline, 52 weeks
Change in quality of life as assessed by the Parkinson's Disease Questionnaire (PDQ-39)
The PDQ-39 is a 39 questions Parkinson's Disease self-completed questionnaire that comprises 8 domains: mobility (10 items), activities of daily living (6 items), emotional well-being (6 items), stigma (4 items), social support (3 items), cognition (4 items), communication (3 items) and bodily discomfort (3 items). All items are assumed to impact QoL and must be answered to compute scores for each dimension. Questions are answered based on experiences from the preceding month using a 5-point ordinal scoring system: 0 = never, 1 = occasionally, 2 = sometimes, 3 = often, 4 = always. Each scores range from 0 = never have difficulty to 100 = always have difficulty.
Time frame: baseline, 3 weeks
Change in quality of life as assessed by the Parkinson's Disease Questionnaire (PDQ-39)
The PDQ-39 is a 39 questions Parkinson's Disease self-completed questionnaire that comprises 8 domains: mobility (10 items), activities of daily living (6 items), emotional well-being (6 items), stigma (4 items), social support (3 items), cognition (4 items), communication (3 items) and bodily discomfort (3 items). All items are assumed to impact QoL and must be answered to compute scores for each dimension. Questions are answered based on experiences from the preceding month using a 5-point ordinal scoring system: 0 = never, 1 = occasionally, 2 = sometimes, 3 = often, 4 = always. Each scores range from 0 = never have difficulty to 100 = always have difficulty.
Time frame: baseline, 12 weeks
Change in quality of life as assessed by the Parkinson's Disease Questionnaire (PDQ-39)
The PDQ-39 is a 39 questions Parkinson's Disease self-completed questionnaire that comprises 8 domains: mobility (10 items), activities of daily living (6 items), emotional well-being (6 items), stigma (4 items), social support (3 items), cognition (4 items), communication (3 items) and bodily discomfort (3 items). All items are assumed to impact QoL and must be answered to compute scores for each dimension. Questions are answered based on experiences from the preceding month using a 5-point ordinal scoring system: 0 = never, 1 = occasionally, 2 = sometimes, 3 = often, 4 = always. Each scores range from 0 = never have difficulty to 100 = always have difficulty.
Time frame: baseline, 24 weeks
Change in quality of life as assessed by the Parkinson's Disease Questionnaire (PDQ-39)
The PDQ-39 is a 39 questions Parkinson's Disease self-completed questionnaire that comprises 8 domains: mobility (10 items), activities of daily living (6 items), emotional well-being (6 items), stigma (4 items), social support (3 items), cognition (4 items), communication (3 items) and bodily discomfort (3 items). All items are assumed to impact QoL and must be answered to compute scores for each dimension. Questions are answered based on experiences from the preceding month using a 5-point ordinal scoring system: 0 = never, 1 = occasionally, 2 = sometimes, 3 = often, 4 = always. Each scores range from 0 = never have difficulty to 100 = always have difficulty.
Time frame: baseline, 52 weeks
Change in cognitive function as assessed by the Montreal Cognitive Assessment (MoCA)
The Montreal Cognitive Assessment is a rapid screening instrument for working memory, visual-spatial abilities, executive function, attention, concentration, language and orientation. The total score ranges from 0 to 30; a score of 26 or above is considered normal.
Time frame: baseline, 52 weeks
Change in immunologic response as assessed by plasma concentrations of cytokines
Investigators will assess cytokines associated with inflammation \[interleukin-6 (IL-6), Interleukin-1 beta (IL-1β), Tumor Necrosis Factor beta (TNFβ)\]; cell growth and differentiation \[Brain-derived neurotrophic factor (BDNF), Granulocyte-macrophage colony-stimulating factor (GM-CSF)\]; monocyte migration \[Fractalkine, Eotaxin, monocyte chemotactic protein 1 (MCP-1), Macrophage Inflammatory Protein 1 beta (MIP-1β)\]; and adaptive immune response \[interleukin 12 subunit beta (IL-12p40), interleukin 7 (IL-7), interleukin 9 (IL-9), interleukin 4 (IL-4)\] will be measured.
Time frame: baseline, 3 weeks
Change in immunologic response as assessed by plasma concentrations of cytokines
Investigators will assess cytokines associated with inflammation \[interleukin-6 (IL-6), Interleukin-1 beta (IL-1β), Tumor Necrosis Factor beta (TNFβ)\]; cell growth and differentiation \[Brain-derived neurotrophic factor (BDNF), Granulocyte-macrophage colony-stimulating factor (GM-CSF)\]; monocyte migration \[Fractalkine, Eotaxin, monocyte chemotactic protein 1 (MCP-1), Macrophage Inflammatory Protein 1 beta (MIP-1β)\]; and adaptive immune response \[interleukin 12 subunit beta (IL-12p40), interleukin 7 (IL-7), interleukin 9 (IL-9), interleukin 4 (IL-4)\] will be measured.
Time frame: baseline, 12 weeks
Change in immunologic response as assessed by plasma concentrations of cytokines
Investigators will assess cytokines associated with inflammation \[interleukin-6 (IL-6), Interleukin-1 beta (IL-1β), Tumor Necrosis Factor beta (TNFβ)\]; cell growth and differentiation \[Brain-derived neurotrophic factor (BDNF), Granulocyte-macrophage colony-stimulating factor (GM-CSF)\]; monocyte migration \[Fractalkine, Eotaxin, monocyte chemotactic protein 1 (MCP-1), Macrophage Inflammatory Protein 1 beta (MIP-1β)\]; and adaptive immune response \[interleukin 12 subunit beta (IL-12p40), interleukin 7 (IL-7), interleukin 9 (IL-9), interleukin 4 (IL-4)\] will be measured.
Time frame: baseline, 24 weeks
Change in immunologic response as assessed by plasma concentrations of cytokines
Investigators will assess cytokines associated with inflammation \[interleukin-6 (IL-6), Interleukin-1 beta (IL-1β), Tumor Necrosis Factor beta (TNFβ)\]; cell growth and differentiation \[Brain-derived neurotrophic factor (BDNF), Granulocyte-macrophage colony-stimulating factor (GM-CSF)\]; monocyte migration \[Fractalkine, Eotaxin, monocyte chemotactic protein 1 (MCP-1), Macrophage Inflammatory Protein 1 beta (MIP-1β)\]; and adaptive immune response \[interleukin 12 subunit beta (IL-12p40), interleukin 7 (IL-7), interleukin 9 (IL-9), interleukin 4 (IL-4)\] will be measured.
Time frame: baseline, 52 weeks
Change in suicidal ideation or behaviors as assessed by and Columbia Suicide Severity Rating Scale (CSSRS)
The CSSRS rating scale is a set of questions directed towards eliciting verbalization of suicidal feelings or actions
Time frame: Screening, 3 weeks, 12 weeks, 24 weeks, 52 weeks