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Phase IIa Randomized Placebo Controlled Trial: Mesenchymal Stem Cells as a Disease-modifying Therapy for iPD

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04506073
Recruitment Status : Recruiting
First Posted : August 10, 2020
Last Update Posted : November 12, 2020
Sponsor:
Collaborator:
Michael J. Fox Foundation for Parkinson's Research
Information provided by (Responsible Party):
Mya Schiess, The University of Texas Health Science Center, Houston

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).

Condition or disease Intervention/treatment Phase
Parkinson's Disease Drug: MSC+placebo Drug: MSC Drug: Placebo Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 45 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Official Title: Allogeneic Bone Marrow-derived Mesenchymal Stem Cells as a Disease-modifying Therapy for Idiopathic Parkinson's Disease: Phase IIa Double-blind Randomized Placebo Controlled Trial
Estimated Study Start Date : November 9, 2020
Estimated Primary Completion Date : May 1, 2023
Estimated Study Completion Date : May 1, 2023

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: MSC+placebo
2 treatment doses + 1 placebo 3 months apart
Drug: MSC+placebo
2 infusions of 10 X 10^6 MSC/kg and 1 placebo every 3 months.
Other Name: allogeneic mesenchymal stem cell or similar placebo

Experimental: MSC
3 treatment doses 3 months apart
Drug: MSC
3 infusions of 10 X 10^6 MSC/kg every 3 months.
Other Name: allogeneic mesenchymal stem cell

Placebo Comparator: Placebo
3 placebo doses 3 months apart
Drug: Placebo
3 infusions of placebo every 3 months. Placebo will be identical to the investigational product but will not contain MSCs.
Other Name: Similar placebo




Primary Outcome Measures :
  1. 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 ]
  2. 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 ]
  3. 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 ]
  4. 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 ]
  5. 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 ]
  6. 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 ]
  7. 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 Measures :
  1. Safety and tolerability as measured by serious adverse reactions. [ Time Frame: Baseline,week 7,week 20,week 29,week 39,week 78 ]
  2. Safety and tolerability as measured by immunologic responses. [ Time Frame: Baseline,week 7,week 20,week 29,week 39,week 78 ]
    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.

  3. Motor function as measured by the Timed-Up-and-Go (TUG) scale [ Time Frame: Baseline,week 7,week 20,week 29,week 39,week 52,week 78 ]
    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

  4. 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 ]
  5. 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 ]
  6. 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 ]
  7. 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 ]
  8. 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 ]
  9. Cognitive function as measured by the the change in Montreal Cognitive Assessment (MoCA) [ Time Frame: Baseline,week 29,week 78 ]
  10. Behavioral changes as measured by the Columbia Suicide Severity Rating Scale (C-SSRS) [ Time Frame: Baseline,week 7,week 20,week 29,week 39,week 52,week 78 ]
    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.

  11. Behavioral changes as measured by the Geriatric Depression Scale-Short Form (GDS-SF) [ Time Frame: Baseline,week 7,week 20,week 29,week 39,week 52,week 78 ]
    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 .

  12. 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 ]
  13. Measurement of putative paracrine mechanism of MSCs using neuroimaging [ Time Frame: Baseline,week 29,week 78 ]
  14. Measurement of putative paracrine mechanism of MSCs as measured by concentration of cytokines in patient blood sample. [ Time Frame: Baseline,week 7,week 20,week 29,week 39,week 78 ]
    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.

  15. Measurement of putative paracrine mechanism of MSCs as measured by concentration of chemokines in patient blood sample. [ Time Frame: Baseline,week 7,week 20,week 29,week 39,week 78 ]
    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.

  16. Measurement of putative paracrine mechanism of MSCs as measured by concentration of growth factors [ Time Frame: Baseline,week 7,week 20,week 29,week 39,week 78 ]
    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.

  17. Measurement of putative paracrine mechanism of MSCs as measured by concentration of neurotransmitters [ Time Frame: Baseline,week 7,week 20,week 29,week 39,week 78 ]
    Examples of these are homovanillic acid and 5-hydroxytryptamine. These will be measured in CSF and blood by ELISA.

  18. 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 ]
  19. Measurement of putative paracrine mechanism of MSCs as measured by alpha-synuclein oligomers in the cerebral spinal fluid [ Time Frame: Baseline,week 39 ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   50 Years to 79 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04506073


Contacts
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Contact: Mya C Schiess, MD (713) 500-7051 Mya.C.Schiess@uth.tmc.edu
Contact: Vanessa Thyne, MS (713)500-7127 vanessa.k.thyne@uth.tmc.edu

Locations
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United States, Texas
The University of Texas Health Science Center at Houston Recruiting
Houston, Texas, United States, 77030
Contact: Mya Schiess, MD    713-500-7051    Mya.C.Schiess@uth.tmc.edu   
Contact: Vanessa Thyne, MS    (713)500-7127    vanessa.k.thyne@uth.tmc.edu   
Sponsors and Collaborators
The University of Texas Health Science Center, Houston
Michael J. Fox Foundation for Parkinson's Research
Investigators
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Principal Investigator: Mya C Schiess, MD The University of Texas Health Science Center, Houston
Publications:

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Responsible Party: Mya Schiess, Professor and Adriana Blood Chair in Neurology, The University of Texas Health Science Center, Houston
ClinicalTrials.gov Identifier: NCT04506073    
Other Study ID Numbers: HSC-MS-20-0150
First Posted: August 10, 2020    Key Record Dates
Last Update Posted: November 12, 2020
Last Verified: November 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Mya Schiess, The University of Texas Health Science Center, Houston:
Stem Cells
Mesenchymal stem cells
Inflammatory markers
Additional relevant MeSH terms:
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Parkinson Disease
Parkinsonian Disorders
Basal Ganglia Diseases
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Movement Disorders
Neurodegenerative Diseases