Clinical trial NCT02611167: Allogeneic Bone Marrow-Derived Mesenchymal Stem Cell Therapy for Idiopathic Parkinson's Disease
Official title: Pilot Phase I Study of Allogeneic Bone Marrow-Derived Mesenchymal Stem Cell Therapy for Idiopathic Parkinson's Disease
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Parkinson's Disease
Keywords: mesenchymal stem cells
Lead sponsor: The University of Texas Health Science Center, Houston
Sponsor class: OTHER
First posted: 2015-11-20
Enrollment: 20
Sex: ALL
Minimum age (years): 45
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: 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).

Detailed description: 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.

Eligibility criteria: Inclusion Criteria:

* Men and women between the ages of 45 and 70. The 45-year-old age cutoff ensures that we do not enroll juvenile PD patients.
* Diagnosis of Parkinson disease by the United Kingdom (UK) brain bank criteria including the presence of 2 cardinal signs of PD plus bradykinesia. Diagnosis will be confirmed by the PI or other specialists in Movement Disorders and based on medical history, physical and neurological exams. Patients should have an asymmetric onset, unilateral symptoms and a negative pull test. (See Appendix A)
* Moderate to severe microsmia (UPSIT \<29).
* A modified Hoehn and Yahr stage of 3 or less in the levodopa OFF state. (See Appendix B)
* Diagnosis of PD between 4 to 7 years.
* Robust response to dopaminergic therapy (defined as greater than 33% reduction in symptoms (on the Unified Parkinson's Disease Rating Scale; UPDRS) when measured in the ON medicine state compared to OFF state.
* If subject is taking any central nervous system acting medications (e.g., benzodiazepines, antidepressants, hypnotics) regimen must be optimized and stable for 90 days prior to the screening visit.
* A stable Parkinson's disease symptomatic therapy for at least 90 days prior to screening and not projected to require additional Parkinson's disease symptomatic therapy for at least one year from the baseline visit.
* Women of childbearing potential will be required to use a reliable form of contraception from 30 days prior to baseline visit until 6 months after the final dose of the study drug.

Exclusion Criteria:

* Atypical or drug-induced Parkinsonism.
* A UPDRS rest tremor score of 3 or greater for any limb.
* A Montreal Cognitive Assessment (MoCA) score of less than 25. (See Appendix C)
* Clinical features of psychosis or refractory hallucinations.
* Uncontrolled seizure disorder, defined as a seizure within the last 6 months.
* Developmental delay.
* Chronic kidney disease defined as glomerular filtration rate (GFR) \< 50 mL/min/m2.
* Hepatic disease or altered liver function as defined by alanine transaminase (ALT) \>150 U/L and or T. Bilirubin \>1.6 mg/dl at admission.
* Presence of clinically refractory orthostatic hypotension at the screening or baseline visit defined as greater than or equal to 20 mmHg change in systolic BP and greater than or equal to 10 mmHg change in diastolic BP from sitting position to standing after 2 minutes that does not respond to medical treatment or baseline sitting BP less than 90/60.
* History of congestive heart failure, clinically significant bradycardia, presence of 2nd or 3rd degree atrioventricular block.
* Pulmonary disease: chronic obstructive 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 (Cancer free for at least 5 years is permitted; skin cancers, except for melanoma, are permitted).
* Any diagnosis of autoimmune disease or immunocompromised state, including chemotherapy administration within last 3 years or current immunosuppression as defined by white blood cell (WBC) \<3 x 103 cells/ml.
* History of strokes or traumatic brain injury.
* Major surgery within the previous 3 months or planned in the ensuing 6 months.
* Clinically significant abnormalities in the Screening Visit laboratory studies.
* History of use of an investigational drug within 30 days prior to the screening visit.
* History of brain surgery for PD.
* Unable to return for follow-up visits for clinical evaluation, laboratory studies, or imaging evaluation.
* Substance abuse disorder.
* Active anticoagulation treatment.
* Any other condition that the investigator feels would pose a significant hazard to the patient if enrolled or complicate the study assessments.

Primary outcomes:
measure: 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
timeFrame: 3 weeks after the first infusion
measure: 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
timeFrame: 12 weeks after the first infusion
measure: 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
timeFrame: 24 weeks after the first infusion
measure: 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
timeFrame: 52 weeks after the first infusion
Secondary outcomes:
measure: Change in motor function as assessed by the Unified Parkinson's Disease Rating Scale (UPDRS) Total score
timeFrame: baseline, 3 weeks
measure: Change in motor function as assessed by the Unified Parkinson's Disease Rating Scale (UPDRS) Total score
timeFrame: baseline, 12 weeks
measure: Change in motor function as assessed by the Unified Parkinson's Disease Rating Scale (UPDRS) Total score
timeFrame: baseline, 24 weeks
measure: Change in motor function as assessed by the Unified Parkinson's Disease Rating Scale (UPDRS) Total score
timeFrame: baseline, 52 weeks
measure: Change in motor function as assessed by the UPDRS Motor score
timeFrame: baseline, 3 weeks
measure: Change in motor function as assessed by the UPDRS Motor score
timeFrame: baseline, 12 weeks
measure: Change in motor function as assessed by the UPDRS Motor score
timeFrame: baseline, 24 weeks
measure: Change in motor function as assessed by the UPDRS Motor score
timeFrame: baseline, 52 weeks
measure: Change in motor function as assessed by Timed-Up-and-Go (TUG)
timeFrame: baseline, 3 weeks
measure: Change in motor function as assessed by Timed-Up-and-Go (TUG)
timeFrame: baseline, 12 weeks
measure: Change in motor function as assessed by Timed-Up-and-Go (TUG)
timeFrame: baseline, 24 weeks
measure: Change in motor function as assessed by Timed-Up-and-Go (TUG)
timeFrame: baseline, 52 weeks
measure: Change in disability as measured by the Modified Hoehn and Yahr Scale
timeFrame: baseline, 3 weeks
measure: Change in disability as measured by the Modified Hoehn and Yahr Scale
timeFrame: baseline, 12 weeks
measure: Change in disability as measured by the Modified Hoehn and Yahr Scale
timeFrame: baseline, 24 weeks
measure: Change in disability as measured by the Modified Hoehn and Yahr Scale
timeFrame: baseline, 52 weeks
measure: functional connectivity between substantia nigra and dorsal striatum as assessed by resting state functional magnetic resonance imaging (fMRI)
timeFrame: baseline
measure: perfusion as assessed by arterial spin-labeled (ASL) perfusion MRI
timeFrame: baseline
measure: structural connectivity as assessed by diffusion-weighted MRI for diffusion tensor image (DTI) analysis
timeFrame: baseline
measure: volume of subcortical structures as assessed by T1- and T2- weighted MRI with Fluid Attenuated Inversion Recovery
timeFrame: baseline
measure: cortical thickness as assessed by T1- and T2- weighted MRI with Fluid Attenuated Inversion Recovery
timeFrame: baseline
measure: Change in gross brain structure as assessed by T1- and T2- weighted MRI with Fluid Attenuated Inversion Recovery
timeFrame: baseline
measure: Change in brain activity as assessed by task state fMRI
timeFrame: baseline
measure: Change in quality of life as assessed by the modified Schwab and England activities of daily living (ADL) score
timeFrame: baseline, 3 weeks
measure: Change in quality of life as assessed by the modified Schwab and England activities of daily living (ADL) score
timeFrame: baseline, 12 weeks
measure: Change in quality of life as assessed by the modified Schwab and England activities of daily living (ADL) score
timeFrame: baseline, 24 weeks
measure: Change in quality of life as assessed by the modified Schwab and England activities of daily living (ADL) score
timeFrame: baseline, 52 weeks
measure: Change in quality of life as assessed by the Parkinson's Disease Questionnaire (PDQ-39)
timeFrame: baseline, 3 weeks
measure: Change in quality of life as assessed by the Parkinson's Disease Questionnaire (PDQ-39)
timeFrame: baseline, 12 weeks
measure: Change in quality of life as assessed by the Parkinson's Disease Questionnaire (PDQ-39)
timeFrame: baseline, 24 weeks
measure: Change in quality of life as assessed by the Parkinson's Disease Questionnaire (PDQ-39)
timeFrame: baseline, 52 weeks
measure: Change in cognitive function as assessed by the Montreal Cognitive Assessment (MoCA)
timeFrame: baseline, 52 weeks
measure: Change in immunologic response as assessed by plasma concentrations of cytokines
timeFrame: baseline, 3 weeks
measure: Change in immunologic response as assessed by plasma concentrations of cytokines
timeFrame: baseline, 12 weeks
measure: Change in immunologic response as assessed by plasma concentrations of cytokines
timeFrame: baseline, 24 weeks
measure: Change in immunologic response as assessed by plasma concentrations of cytokines
timeFrame: baseline, 52 weeks
measure: Change in suicidal ideation or behaviors as assessed by and Columbia Suicide Severity Rating Scale (CSSRS)
timeFrame: Screening, 3 weeks, 12 weeks, 24 weeks, 52 weeks
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 Schiess, MD
role: PRINCIPAL_INVESTIGATOR
References: