Phase IIa Randomized Placebo Controlled Trial: Mesenchymal Stem Cells as a Disease-modifying Therapy for Idiopathic Parkinson's Disease

Mya Schiess45 enrolled

Overview

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).

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

TRIPLE

Enrollment

Conditions

Parkinson's Disease

Interventions

Mesenchymal Stem CellsDRUG

1 dose is 10 X 10\^6 MSC/kg

PlaceboDRUG

Placebo will be identical to the investigational product but will not contain mesenchymal stem cells (MSCs).

Eligibility

Sex: ALLMin age: 50 YearsMax age: 79 Years

Medical Language ↔ Plain English

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.

Locations (1)

The University of Texas Health Science Center at Houston

Houston, Texas, United States

Outcomes

Primary Outcomes

Bayesian Mean Estimate of the Proportion of Participants Achieving a ≥5-point Improvement on MDS-UPDRS Part III From Screening to Week 62, Compared Between Each Active MSC Dose Arm and Placebo

The Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part III assesses motor symptoms of Parkinson's disease. . A responder was defined as a participant achieving a ≥5-point improvement (decrease of at least 5 points from screening) at Week 62. Reported are the Bayesian mean estimates of the proportion of participants achieving this response. The 95% confidence interval represents the Bayesian 95% credible interval.

Time frame: From Baseline to Week 62

Secondary Outcomes

Number of Participants With New-onset Organ Failure

New-onset organ failure defined as a significant acute change in the kidney or liver function, leukocytosis, leukopenia or anemia sustained over 3 months; \> 75 % reduction in GFR compared to baseline; altered liver function as defined by ALT \>150 U/L and or total bilirubin \>1.6 mg/dl; or leukopenia defined as \< 4K WBC count or anemia as defined by Hgb \< 12 for men and \< 11 for women.

Time frame: Baseline through week 88

Number of Participants Developing Donor-Specific Anti-HLA Antibodies

Time frame: Baseline through week 88

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 7 meters, turn around, walk back to the chair, and sit down. Time is recorded in seconds, a longer duration of time indicates a worse outcome.

Time frame: Baseline, Week 9, Week 27, Week 40, Week 62, Week 88

Number of Participants With Lifetime Suicidal Ideation (C-SSRS)

The Columbia-Suicide Severity Rating Scale (C-SSRS) is an assessment tool that evaluates suicidal ideation and behavior. Reported is the number of participants with a positive response to the lifetime suicidal ideation question, "Have you actually had any thoughts of killing yourself?"

Data from ClinicalTrials.gov

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Time frame: Baseline

Parkinson's Disease Severity as Assessed by the Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Total Score

The Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) assesses the severity of Parkinson's disease. The total score ranges from 0 to 265, with higher scores indicating greater Parkinson's disease severity and disability.

Time frame: Baseline, Week 9, Week 27, Week 40, Week 62, Week 88

Motor Symptoms of Parkinson's Disease as Assessed by the Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part III Motor Examination Score

The Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part III Motor Examination assesses motor symptoms of Parkinson's disease. The total score ranges from 0 to 132, with higher scores indicating greater motor impairment and more severe Parkinson's disease motor symptoms.

Time frame: Baseline, Week 9, Week 27, Week 40, Week 62, Week 88

Global Measurement of Disability as Measured by the Change in the Screening "Off" Modified Hoehn and Yahr (H&Y)

The Modified Hoehn and Yahr (H\&Y) Scale described the progress of Parkinson's disease. Total score ranges from 0 to 5, with higher scores indicating a worse outcome. The assessment was performed in the "off" medication state, and the score will be reported.

Time frame: Baseline, Week 9, Week 27, Week 40, Week 62, Week 88

Quality of Life as Measured by the Modified Schwab and England Activities of Daily Living Scale (ADL)

The Schwab and England Activities of Daily Living (ADL) Scale assesses functional independence in individuals with Parkinson's disease. Scores range from 0% to 100%, with higher percentages indicating greater independence and better functional ability in activities of daily living.

Time frame: Baseline, Week 9, Week 27, Week 40, Week 62, Week 88

Quality of Life as Measured by the Parkinson's Disease Questionnaire-39 (PDQ-39)

The Parkinson's Disease Questionnaire-39 (PDQ-39) assesses health-related quality of life in individuals with Parkinson's disease. Total scores range from 0 to 100, with higher scores indicating poorer quality of life.

Time frame: Baseline, Week 9, Week 27, Week 40, Week 62, Week 88

Quality of Life as Measured by the EuroQol- 5 Dimension (EQ-5D) Index Score

The EuroQol- 5 Dimension (EQ-5D) assesses quality of life. The total score ranges between 0 to 1, a higher score indicating better quality of life.

Time frame: Baseline, Week 9, Week 27, Week 40, Week 62, Week 88

Non- Motor Symptoms as Measured by the Non-Motor Symptoms Questionnaire (NMSQ)

The Non-Motor Symptoms Questionnaire (NMSQ) assesses the presence of non-motor symptoms associated with Parkinson's disease. Total score ranges from 0 to 30, with a higher score indicating a greater number of non-motor symptoms.

Time frame: Baseline, Week 9, Week 27, Week 40, Week 62, Week 88

Olfactory Function as Assessed by the University of Pennsylvania Smell Identification Test (UPSIT-40) Score

The University of Pennsylvania Smell Identification Test (UPSIT-40) assesses olfactory function. The total score ranges from 0 to 40 with a higher score indicating better olfactory function.

Time frame: Baseline, Week 49, Week 88

Cognitive Function as Measured by the Montreal Cognitive Assessment (MoCA)

The Montreal Cognitive Assessment (MoCA) assesses cognitive function. The total score ranges from 0 to 30, a higher score indicates better cognitive function.

Time frame: Baseline, Week 49, Week 88

Anxiety as Assessed by the Parkinson Anxiety Scale (PAS) Score

The Parkinson Anxiety Scale (PAS) assesses anxiety symptoms in individuals with Parkinson's disease. The total score ranges from 0 to 48, with higher scores indicating greater anxiety severity.

Time frame: Baseline, Week 9, Week 27, Week 40, Week 62, Week 88

Depressive Symptoms as Assessed by the Geriatric Depression Scale-Short Form (GDS-SF) Score

The Geriatric Depression Scale-Short Form (GDS-SF) assesses depressive symptoms. The total score ranges from 0 to 15, with higher scores indicating greater depressive symptom severity.

Time frame: Baseline, Week 9, Week 27, Week 40, Week 62, Week 88

Number of Participants Reporting Suicidal Ideation Since Last Visit

The Columbia-Suicide Severity Rating Scale (C-SSRS) assesses suicidal ideation and behavior. Reported is the number of participants with a positive response to the suicidal ideation question, "Have you actually had any thoughts of killing yourself?" since the previous study visit.

Time frame: Week 9, Week 27, Week 49, Week 62, Week 88