Allogeneic Bone Marrow-Derived Mesenchymal Stem Cell Therapy for Idiopathic Parkinson's Disease

• Register: ClinicalTrials.gov
• Last refreshed on: 11 December 2023
• Main ID: NCT02611167
• Date of registration: 11/11/2015
• Prospective Registration: Yes
• Primary sponsor: The University of Texas Health Science Center, Houston
• Public title: Allogeneic Bone Marrow-Derived Mesenchymal Stem Cell Therapy for Idiopathic Parkinson's Disease
• Scientific title: Pilot Phase I Study of Allogeneic Bone Marrow-Derived Mesenchymal Stem Cell Therapy for Idiopathic Parkinson's Disease
• Date of first enrolment: November 1, 2017
• Target sample size: 20
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/ct2/show/NCT02611167
• Study type: Interventional
• Study design: Allocation: Non-Randomized. Intervention model: Sequential Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: Phase 1

Countries of recruitment

United States

Contacts

• Name: Mya Schiess, MD
• Affiliation: The University of Texas Health Science Center, Houston

Key inclusion & exclusion 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.



Age minimum: 45 Years
Age maximum: 70 Years
Gender: All

Health Condition(s) or Problem(s) studied

Parkinson's Disease

Intervention(s)

Biological: Allogeneic bone marrow-derived MSCs (1 x 10 6 MSC/kg)

Biological: Allogeneic bone marrow-derived MSCs (6 x 10 6 MSC/kg)

Biological: Allogeneic bone marrow-derived MSCs (10 x 10 6 MSC/kg)

Biological: Allogeneic bone marrow-derived MSCs (3 x 10 6 MSC/kg)

Primary Outcome(s)

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 [Time Frame: 3 weeks after the first infusion]

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 [Time Frame: 12 weeks after the first infusion]

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 [Time Frame: 52 weeks after the first infusion]

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 [Time Frame: 24 weeks after the first infusion]

Secondary Outcome(s)

Change in disability as measured by the Modified Hoehn and Yahr Scale [Time Frame: baseline, 24 weeks]

Change in immunologic response as assessed by plasma concentrations of cytokines [Time Frame: baseline, 3 weeks]

Change in motor function as assessed by the Unified Parkinson's Disease Rating Scale (UPDRS) Total score [Time Frame: baseline, 12 weeks]

Change in immunologic response as assessed by plasma concentrations of cytokines [Time Frame: baseline, 52 weeks]

Change in motor function as assessed by the UPDRS Motor score [Time Frame: baseline, 52 weeks]

Change in motor function as assessed by the UPDRS Motor score [Time Frame: baseline, 3 weeks]

cortical thickness as assessed by T1- and T2- weighted MRI with Fluid Attenuated Inversion Recovery [Time Frame: baseline]

structural connectivity as assessed by diffusion-weighted MRI for diffusion tensor image (DTI) analysis [Time Frame: baseline]

Change in quality of life as assessed by the modified Schwab and England activities of daily living (ADL) score [Time Frame: baseline, 12 weeks]

Change in quality of life as assessed by the modified Schwab and England activities of daily living (ADL) score [Time Frame: baseline, 24 weeks]

Change in quality of life as assessed by the modified Schwab and England activities of daily living (ADL) score [Time Frame: baseline, 52 weeks]

functional connectivity between substantia nigra and dorsal striatum as assessed by resting state functional magnetic resonance imaging (fMRI) [Time Frame: baseline]

Change in immunologic response as assessed by plasma concentrations of cytokines [Time Frame: baseline, 12 weeks]

Change in motor function as assessed by the Unified Parkinson's Disease Rating Scale (UPDRS) Total score [Time Frame: baseline, 24 weeks]

Change in disability as measured by the Modified Hoehn and Yahr Scale [Time Frame: baseline, 3 weeks]

Change in motor function as assessed by the UPDRS Motor score [Time Frame: baseline, 24 weeks]

Change in motor function as assessed by the Unified Parkinson's Disease Rating Scale (UPDRS) Total score [Time Frame: baseline, 52 weeks]

Change in cognitive function as assessed by the Montreal Cognitive Assessment (MoCA) [Time Frame: baseline, 52 weeks]

Change in gross brain structure as assessed by T1- and T2- weighted MRI with Fluid Attenuated Inversion Recovery [Time Frame: baseline]

Change in brain activity as assessed by task state fMRI [Time Frame: baseline]

Change in disability as measured by the Modified Hoehn and Yahr Scale [Time Frame: baseline, 12 weeks]

Change in motor function as assessed by the Unified Parkinson's Disease Rating Scale (UPDRS) Total score [Time Frame: baseline, 3 weeks]

Change in motor function as assessed by Timed-Up-and-Go (TUG) [Time Frame: baseline, 3 weeks]

Change in quality of life as assessed by the Parkinson's Disease Questionnaire (PDQ-39) [Time Frame: baseline, 12 weeks]

Change in quality of life as assessed by the Parkinson's Disease Questionnaire (PDQ-39) [Time Frame: baseline, 3 weeks]

Change in motor function as assessed by the UPDRS Motor score [Time Frame: baseline, 12 weeks]

Change in quality of life as assessed by the modified Schwab and England activities of daily living (ADL) score [Time Frame: baseline, 3 weeks]

Change in quality of life as assessed by the Parkinson's Disease Questionnaire (PDQ-39) [Time Frame: baseline, 24 weeks]

Change in suicidal ideation or behaviors as assessed by and Columbia Suicide Severity Rating Scale (CSSRS) [Time Frame: Screening, 3 weeks, 12 weeks, 24 weeks, 52 weeks]

volume of subcortical structures as assessed by T1- and T2- weighted MRI with Fluid Attenuated Inversion Recovery [Time Frame: baseline]

perfusion as assessed by arterial spin-labeled (ASL) perfusion MRI [Time Frame: baseline]

Change in disability as measured by the Modified Hoehn and Yahr Scale [Time Frame: baseline, 52 weeks]

Change in immunologic response as assessed by plasma concentrations of cytokines [Time Frame: baseline, 24 weeks]

Change in motor function as assessed by Timed-Up-and-Go (TUG) [Time Frame: baseline, 12 weeks]

Change in motor function as assessed by Timed-Up-and-Go (TUG) [Time Frame: baseline, 24 weeks]

Change in motor function as assessed by Timed-Up-and-Go (TUG) [Time Frame: baseline, 52 weeks]

Change in quality of life as assessed by the Parkinson's Disease Questionnaire (PDQ-39) [Time Frame: baseline, 52 weeks]

Secondary ID(s)

HSC-MS-16-0026

Source(s) of Monetary Support

Please refer to primary and secondary sponsors