Back to resultsPhase IIa Randomized Placebo Controlled Trial: Mesenchymal Stem Cells as a Disease-modifying Therapy for iPD
Primary Purpose
Parkinson's Disease
Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
MSC+placebo
MSC
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Parkinson's Disease focused on measuring Stem Cells, Mesenchymal stem cells, Inflammatory markers
Eligibility Criteria
Inclusion Criteria:
- Diagnosis of Parkinson's disease by the UK brain bank criteria including the presence of 2 cardinal signs of PD plus bradykinesia.
- Mild microsomia to anosmia.
- A modified Hoehn and Yahr stage of 3 or less.
- Date of diagnosis of PD between 3 to 10 years
- Robust response to dopaminergic therapy.
Exclusion Criteria:
- Atypical, vascular, or drug-induced Parkinsonism.
- An atypical DAT scan or MRI supporting an alternative explanation for PD symptoms.
- Patient not on levodopa containing medications.
- Clinical features of psychosis or refractory hallucinations.
- A Montreal Cognitive Assessment (MoCA) score of less than 25.
- Uncontrolled seizure disorder.
- Abnormal Kidney and liver function.
- Presence of clinically refractory orthostatic hypotension at the screening or baseline visit.
- Body mass index of greater than or equal to 35.
- Cardiac disease: History of congestive heart failure, clinically significant bradycardia, presence of 2nd, or 3rd-degree atrioventricular block.
- Pulmonary disease: COPD with oxygen-requirement at rest or with ambulation; or moderate to severe asthma.
- Active malignancy or diagnosis of malignancy within 5 years prior to the start of screening
- Any current suicidal ideation or behaviors.
- Any diagnosis of autoimmune disease or immunocompromised state
- History of medium or large size vessel cerebrovascular accidents.
- History of traumatic brain injury with loss of consciousness and residual neurologic symptoms.
- Major surgery within the previous 3 months or planned in the ensuing 6 months.
- History of use of an investigational drug within 90 days prior to the screening visit.
- History of brain surgery for PD.
- Substance abuse disorder.
- Active anticoagulation treatment and/or abnormal INR.
Sites / Locations
- The University of Texas Health Science Center at Houston
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Experimental
Experimental
Placebo Comparator
Arm Label
MSC+placebo
MSC
Placebo
Arm Description
2 treatment doses + 1 placebo 3 months apart
3 treatment doses 3 months apart
3 placebo doses 3 months apart
Outcomes
Primary Outcome Measures
Safest number of effective doses of MSC as measured by the Part III of the Movement Disorder Society Unified Parkinson's disease Rating Scale (MDS-UPDRS) scale
Safest number of effective doses of MSC as measured by the Part III of the Movement Disorder Society Unified Parkinson's disease Rating Scale (MDS-UPDRS) scale
Safest number of effective doses of MSC as measured by the Part III of the Movement Disorder Society Unified Parkinson's disease Rating Scale (MDS-UPDRS) scale
Safest number of effective doses of MSC as measured by the Part III of the Movement Disorder Society Unified Parkinson's disease Rating Scale (MDS-UPDRS) scale
Safest number of effective doses of MSC as measured by the Part III of the Movement Disorder Society Unified Parkinson's disease Rating Scale (MDS-UPDRS) scale
Safest number of effective doses of MSC as measured by the Part III of the Movement Disorder Society Unified Parkinson's disease Rating Scale (MDS-UPDRS) scale
Safest number of effective doses of MSC as measured by the Part III of the Movement Disorder Society Unified Parkinson's disease Rating Scale (MDS-UPDRS) scale
Secondary Outcome Measures
Safety and tolerability as measured by serious adverse reactions.
Safety and tolerability as measured by immunologic responses.
Donor specific antibodies (DSA) in serum of patients will be measured and compared to baseline to determine if there is a development of antibody response to donor HLA (human leukocyte antigen). This will determine if there is a possibility of anti-donor alloimmune response after the first or second infusion of MSC, which might lead to a subsequent antibody-mediated rejection (AMR) with the following infusion. Testing will be done at the these time points to determine if 2nd or 3rd infusions will continue.
Motor function as measured by the Timed-Up-and-Go (TUG) scale
This test uses the time that a person takes to rise from a chair, walk three meters, turn around, walk back to the chair, and sit down. A longer duration of time indicates a worse outcome
Global measurement of disability as measured by the change in the screening "Off" modified Hoehn and Yahr (H&Y)
Quality of life as measured by the modified Schwab and England activities of daily living scale (ADL)
Quality of life as measured by the Parkinson's Disease Questionnaire 39 (PDQ-39)
Quality of life as measured by the EuroQol- 5 Dimension (EQ-5D)
Non-motor symtoms as measured by the The University of Pennsylvania Smell Identification Test (UPSIT- 40 odor test booklet).
Cognitive function as measured by the the change in Montreal Cognitive Assessment (MoCA)
Behavioral changes as measured by the Columbia Suicide Severity Rating Scale (C-SSRS)
The Columbia-Suicide Severity Rating Scale (C-SSRS) is an assessment tool that evaluates suicidal ideation and behavior. It rates an individual's degree of suicidal ideation on a scale, ranging from "wish to be dead" to "active suicidal ideation with specific plan and intent". Exclusionary criteria views 1 or more positive answers in the last month as not eligible for participation. In follow up, one positive response requires further investigation.
Behavioral changes as measured by the Geriatric Depression Scale-Short Form (GDS-SF)
The Geriatric Depression Scale Short form (GDS-SF) is a 15-item screening tool that is used to identify depression in older adults. Answers indicating depression are in bold and italicized; score one point for each bold one selected. A score of 0 to 5 is normal. A score greater than 5 suggests depression and requires evaluation, whereas a score of 10 or greater would require evaluation for treatment .
Behavioral changes as measured by the Parkinson Anxiety Scale (PAS)
Measurement of putative paracrine mechanism of MSCs using neuroimaging
Measurement of putative paracrine mechanism of MSCs as measured by concentration of cytokines in patient blood sample.
Examples of these are IL-1beta, IL-6, TNF-alpha, COX-2 and PGE-2. These are measured by Magnetic Bead Panel - Multiplex Assay or ELISA, allowing for specificity in the blood.
Measurement of putative paracrine mechanism of MSCs as measured by concentration of chemokines in patient blood sample.
Examples of these are CCL2 (MCP-1), CCL7 (MCP-3), CCL11 (Eotaxin) CCL2 (MDC), CXCL10 (IP-10), CX3CL1 (Fractalkine). These will be measured by Magnetic Bead Panel - Multiplex Assay or ELISA, allowing for specificity in the blood.
Measurement of putative paracrine mechanism of MSCs as measured by concentration of growth factors
Examples of these are Glial Derived Neurotrophic Factor, Brain Derived Neurotrophic Factor and Vascular Epidermal Growth Factor . These will be measured by ELISA specific to blood and CSF.
Measurement of putative paracrine mechanism of MSCs as measured by concentration of neurotransmitters
Examples of these are homovanillic acid and 5-hydroxytryptamine. These will be measured in CSF and blood by ELISA.
Measurement of putative paracrine mechanism of MSCs as measured by alpha-synuclein oligomers in the blood (serum or plasma)
Measurement of putative paracrine mechanism of MSCs as measured by alpha-synuclein oligomers in the cerebral spinal fluid
Full Information
NCT ID
NCT04506073
First Posted
July 16, 2020
Last Updated
September 7, 2023
Sponsor
The University of Texas Health Science Center, Houston
Collaborators
Michael J. Fox Foundation for Parkinson's Research
1. Study Identification
Unique Protocol Identification Number
NCT04506073
Brief Title
Phase IIa Randomized Placebo Controlled Trial: Mesenchymal Stem Cells as a Disease-modifying Therapy for iPD
Official Title
A Randomized, Double-blind, Placebo-controlled Trial of Allogeneic Bone Marrow-derived Mesenchymal Stem Cells as a Disease-modifying Therapy for Idiopathic Parkinson's Disease
Study Type
Interventional
2. Study Status
Record Verification Date
September 2023
Overall Recruitment Status
Completed
Study Start Date
November 9, 2020 (Actual)
Primary Completion Date
July 30, 2023 (Actual)
Study Completion Date
July 30, 2023 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
The University of Texas Health Science Center, Houston
Collaborators
Michael J. Fox Foundation for Parkinson's Research
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
The purpose of this study is to select the safest and most effective number of repeat doses of allogeneic bone marrow-derived mesenchymal stem cell (MSC) infusions to slow the progression of Parkinson's disease (PD).
Detailed Description
Single site phase IIa study of allogeneic MSC in a double blind randomized control trial as disease modifying therapy for PD. The design includes three treatment arms with 45 patients.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Parkinson's Disease
Keywords
Stem Cells, Mesenchymal stem cells, Inflammatory markers
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigator
Allocation
Randomized
Enrollment
45 (Actual)
8. Arms, Groups, and Interventions
Arm Title
MSC+placebo
Arm Type
Experimental
Arm Description
2 treatment doses + 1 placebo 3 months apart
Arm Title
MSC
Arm Type
Experimental
Arm Description
3 treatment doses 3 months apart
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
3 placebo doses 3 months apart
Intervention Type
Drug
Intervention Name(s)
MSC+placebo
Other Intervention Name(s)
allogeneic mesenchymal stem cell or similar placebo
Intervention Description
2 infusions of 10 X 10^6 MSC/kg and 1 placebo every 3 months.
Intervention Type
Drug
Intervention Name(s)
MSC
Other Intervention Name(s)
allogeneic mesenchymal stem cell
Intervention Description
3 infusions of 10 X 10^6 MSC/kg every 3 months.
Intervention Type
Drug
Intervention Name(s)
Placebo
Other Intervention Name(s)
Similar placebo
Intervention Description
3 infusions of placebo every 3 months. Placebo will be identical to the investigational product but will not contain MSCs.
Primary Outcome Measure Information:
Title
Safest number of effective doses of MSC as measured by the Part III of the Movement Disorder Society Unified Parkinson's disease Rating Scale (MDS-UPDRS) scale
Time Frame
Screening
Title
Safest number of effective doses of MSC as measured by the Part III of the Movement Disorder Society Unified Parkinson's disease Rating Scale (MDS-UPDRS) scale
Time Frame
Week 7, post infusion #1
Title
Safest number of effective doses of MSC as measured by the Part III of the Movement Disorder Society Unified Parkinson's disease Rating Scale (MDS-UPDRS) scale
Time Frame
Week 20, post infusion #2
Title
Safest number of effective doses of MSC as measured by the Part III of the Movement Disorder Society Unified Parkinson's disease Rating Scale (MDS-UPDRS) scale
Time Frame
Week 29, post-infusion #3
Title
Safest number of effective doses of MSC as measured by the Part III of the Movement Disorder Society Unified Parkinson's disease Rating Scale (MDS-UPDRS) scale
Time Frame
Week 39 follow-up
Title
Safest number of effective doses of MSC as measured by the Part III of the Movement Disorder Society Unified Parkinson's disease Rating Scale (MDS-UPDRS) scale
Time Frame
Week 52 follow-up
Title
Safest number of effective doses of MSC as measured by the Part III of the Movement Disorder Society Unified Parkinson's disease Rating Scale (MDS-UPDRS) scale
Time Frame
Week 78 follow-up
Secondary Outcome Measure Information:
Title
Safety and tolerability as measured by serious adverse reactions.
Time Frame
Baseline,week 7,week 20,week 29,week 39,week 78
Title
Safety and tolerability as measured by immunologic responses.
Description
Donor specific antibodies (DSA) in serum of patients will be measured and compared to baseline to determine if there is a development of antibody response to donor HLA (human leukocyte antigen). This will determine if there is a possibility of anti-donor alloimmune response after the first or second infusion of MSC, which might lead to a subsequent antibody-mediated rejection (AMR) with the following infusion. Testing will be done at the these time points to determine if 2nd or 3rd infusions will continue.
Time Frame
Baseline,week 7,week 20,week 29,week 39,week 78
Title
Motor function as measured by the Timed-Up-and-Go (TUG) scale
Description
This test uses the time that a person takes to rise from a chair, walk three meters, turn around, walk back to the chair, and sit down. A longer duration of time indicates a worse outcome
Time Frame
Baseline,week 7,week 20,week 29,week 39,week 52,week 78
Title
Global measurement of disability as measured by the change in the screening "Off" modified Hoehn and Yahr (H&Y)
Time Frame
Baseline,week 7,week 20,week 29,week 39,week 52,week 78
Title
Quality of life as measured by the modified Schwab and England activities of daily living scale (ADL)
Time Frame
Baseline,week 7,week 20,week 29,week 39,week 52,week 78
Title
Quality of life as measured by the Parkinson's Disease Questionnaire 39 (PDQ-39)
Time Frame
Baseline,week 7,week 20,week 29,week 39,week 52,week 78
Title
Quality of life as measured by the EuroQol- 5 Dimension (EQ-5D)
Time Frame
Baseline,week 7,week 20,week 29,week 39,week 52,week 78
Title
Non-motor symtoms as measured by the The University of Pennsylvania Smell Identification Test (UPSIT- 40 odor test booklet).
Time Frame
Baseline,week 29,week 78
Title
Cognitive function as measured by the the change in Montreal Cognitive Assessment (MoCA)
Time Frame
Baseline,week 29,week 78
Title
Behavioral changes as measured by the Columbia Suicide Severity Rating Scale (C-SSRS)
Description
The Columbia-Suicide Severity Rating Scale (C-SSRS) is an assessment tool that evaluates suicidal ideation and behavior. It rates an individual's degree of suicidal ideation on a scale, ranging from "wish to be dead" to "active suicidal ideation with specific plan and intent". Exclusionary criteria views 1 or more positive answers in the last month as not eligible for participation. In follow up, one positive response requires further investigation.
Time Frame
Baseline,week 7,week 20,week 29,week 39,week 52,week 78
Title
Behavioral changes as measured by the Geriatric Depression Scale-Short Form (GDS-SF)
Description
The Geriatric Depression Scale Short form (GDS-SF) is a 15-item screening tool that is used to identify depression in older adults. Answers indicating depression are in bold and italicized; score one point for each bold one selected. A score of 0 to 5 is normal. A score greater than 5 suggests depression and requires evaluation, whereas a score of 10 or greater would require evaluation for treatment .
Time Frame
Baseline,week 7,week 20,week 29,week 39,week 52,week 78
Title
Behavioral changes as measured by the Parkinson Anxiety Scale (PAS)
Time Frame
Baseline,week 7,week 20,week 29,week 39,week 52,week 78
Title
Measurement of putative paracrine mechanism of MSCs using neuroimaging
Time Frame
Baseline,week 29,week 78
Title
Measurement of putative paracrine mechanism of MSCs as measured by concentration of cytokines in patient blood sample.
Description
Examples of these are IL-1beta, IL-6, TNF-alpha, COX-2 and PGE-2. These are measured by Magnetic Bead Panel - Multiplex Assay or ELISA, allowing for specificity in the blood.
Time Frame
Baseline,week 7,week 20,week 29,week 39,week 78
Title
Measurement of putative paracrine mechanism of MSCs as measured by concentration of chemokines in patient blood sample.
Description
Examples of these are CCL2 (MCP-1), CCL7 (MCP-3), CCL11 (Eotaxin) CCL2 (MDC), CXCL10 (IP-10), CX3CL1 (Fractalkine). These will be measured by Magnetic Bead Panel - Multiplex Assay or ELISA, allowing for specificity in the blood.
Time Frame
Baseline,week 7,week 20,week 29,week 39,week 78
Title
Measurement of putative paracrine mechanism of MSCs as measured by concentration of growth factors
Description
Examples of these are Glial Derived Neurotrophic Factor, Brain Derived Neurotrophic Factor and Vascular Epidermal Growth Factor . These will be measured by ELISA specific to blood and CSF.
Time Frame
Baseline,week 7,week 20,week 29,week 39,week 78
Title
Measurement of putative paracrine mechanism of MSCs as measured by concentration of neurotransmitters
Description
Examples of these are homovanillic acid and 5-hydroxytryptamine. These will be measured in CSF and blood by ELISA.
Time Frame
Baseline,week 7,week 20,week 29,week 39,week 78
Title
Measurement of putative paracrine mechanism of MSCs as measured by alpha-synuclein oligomers in the blood (serum or plasma)
Time Frame
Basleline,week 29,week 39,week 78
Title
Measurement of putative paracrine mechanism of MSCs as measured by alpha-synuclein oligomers in the cerebral spinal fluid
Time Frame
Baseline,week 39
10. Eligibility
Sex
All
Minimum Age & Unit of Time
50 Years
Maximum Age & Unit of Time
79 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Diagnosis of Parkinson's disease by the UK brain bank criteria including the presence of 2 cardinal signs of PD plus bradykinesia.
Mild microsomia to anosmia.
A modified Hoehn and Yahr stage of 3 or less.
Date of diagnosis of PD between 3 to 10 years
Robust response to dopaminergic therapy.
Exclusion Criteria:
Atypical, vascular, or drug-induced Parkinsonism.
An atypical DAT scan or MRI supporting an alternative explanation for PD symptoms.
Patient not on levodopa containing medications.
Clinical features of psychosis or refractory hallucinations.
A Montreal Cognitive Assessment (MoCA) score of less than 25.
Uncontrolled seizure disorder.
Abnormal Kidney and liver function.
Presence of clinically refractory orthostatic hypotension at the screening or baseline visit.
Body mass index of greater than or equal to 35.
Cardiac disease: History of congestive heart failure, clinically significant bradycardia, presence of 2nd, or 3rd-degree atrioventricular block.
Pulmonary disease: COPD with oxygen-requirement at rest or with ambulation; or moderate to severe asthma.
Active malignancy or diagnosis of malignancy within 5 years prior to the start of screening
Any current suicidal ideation or behaviors.
Any diagnosis of autoimmune disease or immunocompromised state
History of medium or large size vessel cerebrovascular accidents.
History of traumatic brain injury with loss of consciousness and residual neurologic symptoms.
Major surgery within the previous 3 months or planned in the ensuing 6 months.
History of use of an investigational drug within 90 days prior to the screening visit.
History of brain surgery for PD.
Substance abuse disorder.
Active anticoagulation treatment and/or abnormal INR.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Mya C Schiess, MD
Organizational Affiliation
The University of Texas Health Science Center, Houston
Official's Role
Principal Investigator
Facility Information:
Facility Name
The University of Texas Health Science Center at Houston
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
No
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Phase IIa Randomized Placebo Controlled Trial: Mesenchymal Stem Cells as a Disease-modifying Therapy for iPD
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