Clinical trial NCT04506073: Phase IIa Randomized Placebo Controlled Trial: Mesenchymal Stem Cells as a Disease-modifying Therapy for Idiopathic Parkinson's Disease
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
Overall status: COMPLETED
Phase: PHASE2
Conditions: Parkinson's Disease
Keywords: Stem Cells
Mesenchymal stem cells
Inflammatory markers
Lead sponsor: The University of Texas Health Science Center, Houston
Sponsor class: OTHER
Collaborators: name: Michael J. Fox Foundation for Parkinson's Research
First posted: 2020-08-10
Enrollment: 45
Sex: ALL
Minimum age (years): 50
Maximum age (years): 79
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: 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
timeFrame: Screening
measure: 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
timeFrame: Week 7, post infusion #1
measure: 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
timeFrame: Week 20, post infusion #2
measure: 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
timeFrame: Week 29, post-infusion #3
measure: 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
timeFrame: Week 39 follow-up
measure: 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
timeFrame: Week 52 follow-up
measure: 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
timeFrame: Week 78 follow-up
Secondary outcomes:
measure: Safety and tolerability as measured by serious adverse reactions.
timeFrame: Baseline,week 7,week 20,week 29,week 39,week 78
measure: Safety and tolerability as measured by immunologic responses.
timeFrame: Baseline,week 7,week 20,week 29,week 39,week 78
measure: Motor function as measured by the Timed-Up-and-Go (TUG) scale
timeFrame: Baseline,week 7,week 20,week 29,week 39,week 52,week 78
measure: Global measurement of disability as measured by the change in the screening "Off" modified Hoehn and Yahr (H&Y)
timeFrame: Baseline,week 7,week 20,week 29,week 39,week 52,week 78
measure: Quality of life as measured by the modified Schwab and England activities of daily living scale (ADL)
timeFrame: Baseline,week 7,week 20,week 29,week 39,week 52,week 78
measure: Quality of life as measured by the Parkinson's Disease Questionnaire 39 (PDQ-39)
timeFrame: Baseline,week 7,week 20,week 29,week 39,week 52,week 78
measure: Quality of life as measured by the EuroQol- 5 Dimension (EQ-5D)
timeFrame: Baseline,week 7,week 20,week 29,week 39,week 52,week 78
measure: Non-motor symtoms as measured by the The University of Pennsylvania Smell Identification Test (UPSIT- 40 odor test booklet).
timeFrame: Baseline,week 29,week 78
measure: Cognitive function as measured by the the change in Montreal Cognitive Assessment (MoCA)
timeFrame: Baseline,week 29,week 78
measure: Behavioral changes as measured by the Columbia Suicide Severity Rating Scale (C-SSRS)
timeFrame: Baseline,week 7,week 20,week 29,week 39,week 52,week 78
measure: Behavioral changes as measured by the Geriatric Depression Scale-Short Form (GDS-SF)
timeFrame: Baseline,week 7,week 20,week 29,week 39,week 52,week 78
measure: Behavioral changes as measured by the Parkinson Anxiety Scale (PAS)
timeFrame: Baseline,week 7,week 20,week 29,week 39,week 52,week 78
measure: Measurement of putative paracrine mechanism of MSCs using neuroimaging
timeFrame: Baseline,week 29,week 78
measure: Measurement of putative paracrine mechanism of MSCs as measured by concentration of cytokines in patient blood sample.
timeFrame: Baseline,week 7,week 20,week 29,week 39,week 78
measure: Measurement of putative paracrine mechanism of MSCs as measured by concentration of chemokines in patient blood sample.
timeFrame: Baseline,week 7,week 20,week 29,week 39,week 78
measure: Measurement of putative paracrine mechanism of MSCs as measured by concentration of growth factors
timeFrame: Baseline,week 7,week 20,week 29,week 39,week 78
measure: Measurement of putative paracrine mechanism of MSCs as measured by concentration of neurotransmitters
timeFrame: Baseline,week 7,week 20,week 29,week 39,week 78
measure: Measurement of putative paracrine mechanism of MSCs as measured by alpha-synuclein oligomers in the blood (serum or plasma)
timeFrame: Basleline,week 29,week 39,week 78
measure: Measurement of putative paracrine mechanism of MSCs as measured by alpha-synuclein oligomers in the cerebral spinal fluid
timeFrame: Baseline,week 39
Other outcomes:
Locations:
city: Houston
country: United States
facility: The University of Texas Health Science Center at Houston
state: Texas
Study officials:
affiliation: The University of Texas Health Science Center, Houston
name: Mya C Schiess, MD
role: PRINCIPAL_INVESTIGATOR
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