Clinical trial NCT06858254: Standard Optimization of Stem Cells in Parkinson's Disease and Atypical Parkinsonism
Official title: Standard Optimization of Autologous Stem Cells by Intranasal and Intravenous Administration to Treat Parkinson's Disease and Atypical Parkinsonism
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE1
PHASE2
Conditions: Atypical Parkinsonism
Parkinson Disease (PD)
Keywords: Atypical Parkinsonism
Parkinson-Plus Syndrome
Stem Cells
MSCs
Epigenetics
Metagenomics
Parkinson&#39;s Disease
Lead sponsor: Apeiron Research Center
Sponsor class: OTHER
Collaborators: name: University of Colorado, Boulder
First posted: 2025-03-05
Enrollment: 60
Sex: ALL
Minimum age (years): 40
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to measure outcomes using intranasal and intravenous autologous bone marrow mesenchymal stem cells (BM-MSCs) for Parkinson Disease (PD) and Parkinson's Plus (PPS) patients.

Detailed description: Parkinson Disease (PD) and Parkinson-Plus Syndrome (PPS) are complex neurodegenerative diseases (NDDs) affecting more than 10 million people worldwide. The clinical application of stem cell therapy holds great promise in the treatment of NDDs by promoting regeneration and modulating immune responses with bone marrow aspirate, in particular, holding considerable potential in neural repair and recovery. However, current approaches often rely on university-based laboratories and invasive delivery approaches, raising patient safety, accessibility, and cost concerns. Additionally, NDDs present with distributive and heterogenous pathology, complicating treatment strategies. As pharmaceutical and biotech companies develop targeted stem cell therapies, most focus on localized brain structures rather than targeting PD/PPS systemically. Advancing consensus between scientific research and clinical application is critical for earlier detection in the prodromal phase, identifying epigenetic risk factors, and developing therapeutics that provide a broader, more effective treatment.

The primary objective of this study is to measure outcomes using autologus bone marrow mesenchymal stem cells (BM-MSCs) on motor and non-motor function in persons with PD/PPS. The trial will include 60 participants (40 with PD, 20 with PPS) who will complete 7 scheduled encounters (4 in-person visits, 3 remote visits) that occur every 3 months in an alternating manner. There will be 4 treatment groups (2 PD, 2 PPS) who will be administered intranasal bone marrow aspirate and intravenous bone marrow aspirate in a crossover pattern at three of the four in-person visits (Day 0, 6 months and 12 months).

Eligibility criteria: General Inclusion Criteria:

* Participants aged 40-75 years old with a diagnosis of PD or PPS (DLB, PSP, MSA, CBD with parkinsonism) based upon clinical criteria and standardized testing
* Participants time of documented PD or PPS is \</= 6 years
* Participants with an anticipated survival of at least 3 years in the investigator's opinion
* Participants who are willing and able to give informed consent
* Participants who can comply with the study protocol over the 18-month duration
* Stable medical profile for 60 days prior to the initial intake screening
* Participants can ambulate at least 25m without assistance
* No known history of heparin-induced thrombocytopenia

PD Inclusion Criteria:

* Idiopathic Parkinson's disease patients who meet the MDS's Clinical Diagnostic Criteria for Parkinson's disease
* Responsive to levodopa or dopamine agonists defined by \>/= 33% improvement in "Off"/"On" symptoms by MDS-UPDRS-III
* A modified Hoehn and Yahr stage of \</= 3
* Neuroimaging findings are consistent with PD and absent of atrophy or other brain pathology inconsistent with PD
* "Normal" cognition as assessed by Montreal Cognitive Assessment (MoCA), with a value \>/= 26

PPS Inclusion Criteria:

DLB -

* High probability of cognitive capacity to give informed consent by the Montreal Cognitive Assessment (MoCA), with a value \>/= 23
* Probable DLB - DLB consortium: Two or more core clinical features are present (including features of parkinsonism for the study), or only one core clinical feature is present, but with one or more indicative biomarkers
* Core clinical features:

  * Fluctuating cognition with pronounced variations in attention and alertness
  * Recurrent visual hallucinations that are typically well-formed and detailed Rapid eye movement (REM) sleep behavior disorder (RBD), which may precede cognitive decline
* One or more spontaneous cardinal features of parkinsonism: bradykinesia, resting tremor, or rigidity
* Indicative biomarkers:

  * Reduced dopamine transporter uptake in basal ganglia demonstrated by SPECT/PET
  * Abnormal (low uptake) I-MIBG myocardial scintigraphy
  * Polysomnographic confirmation of REM sleep without atonia

PSP -

* MDS Diagnostic Criteria for probable PSP with predominant parkinsonism (PSP-P)
* Ocular motor dysfunction: vertical supranuclear gaze palsy or slow velocity of vertical saccades or frequent macro square wave jerks ("eyelid-opening apraxia")
* Ocular motor dysfunction + akinetic-rigid, axial predominant, levodopa resistant or with tremor and/or asymmetric and/or levodopa responsive (akinesia)
* "Normal" cognition as assessed by Montreal Cognitive Assessment (MoCA), with a value \>/= 26

MSA -

* MDS Diagnostic Criteria for clinically probable MSA
* Autonomic dysfunction
* Parkinsonism
* Cerebellar syndrome, including at least one of gait ataxia, limb ataxia, cerebellar dysarthria, or oculomotor features
* "Normal" cognition as assessed by Montreal Cognitive Assessment (MoCA), with a value \>/= 26

CBD -

* Chronic progressive course
* Asymmetric onset
* Higher cortical dysfunction: apraxia, speech apraxia, non-fluent aphasia, alien limb phenomena, or cortical sensory loss
* Movement disorder: rigid/akinetic syndrome and either dystonic limb posturing or focal myoclonus in limb, and levodopa resistant
* "Normal" cognition as assessed by Montreal Cognitive Assessment (MoCA), with a value \>/= 26

Exclusion Criteria:

* Other non-PD/PPS Parkinsonism (e.g., drug-induced, vascular parkinsonism)
* No strong familial history of PD/PPS not attributable to environmental exposure or any known genetic predisposition to PD/PPS
* Unable to receive/tolerate neuroimaging (e.g., MRI-incompatible cardiac pacemaker)
* Unable to maintain/tolerate supine position with cervical neck extension
* Active systemic infection or local infection near the lumbar pelvis region
* Any bone marrow aspiration from the pelvis within 6 months of initial screening
* Any musculoskeletal-pelvis contraindications to BMA harvest from the PSIS
* Concurrent enrollment in another PD/PPS study or having taken/received another investigational intervention within 6 weeks of initial screening
* Malignancy diagnosed \</= 2 years prior to initial screening
* History of intracranial or nasopharyngeal surgery deemed detrimental to the participant during the trial, including brain surgery/stereotactic procedure for PD/PPS
* History of electroconvulsive therapy
* Chronic Kidney Disorder (CKD) \> Stage II or eGFR \<60 mL/min
* Autoimmune disease, including:

  * Rheumatoid Arthritis (RA)
  * Systemic Lupus Erythematosus (SLE)
* Any disorders of glucocorticoid excess or diseases requiring systemic steroids or immune-modulating therapies
* Cardiac disease deemed significant:

  * Poorly controlled hypertension (BP \>/=140/90)
  * NYHA class III or IV congestive heart failure
  * History of a significant ventricular arrhythmia
* Obesity class II or higher (BMI \>/= 35)
* Moderate-to-uncontrolled diabetes HbA1c \>/= 7%
* Osteoporosis
* A history of other severe systemic disorders, including significant CVA, TBI, seizure, encephalitis, meningitis, or psychiatric disorder that is deemed potentially harmful to the participant by the PI
* Positive for HIV, HBV, HCV, or syphilis
* Any of the following lab abnormalities:

  * Hematology: Hgb \< 10 g/dl, ANC \< 1.550/L, platelets \< 100,000 /L \>Chemistry: albumin \< 3.0 g/dL, serum creatine \> 1.5 x ULN, total bilirubin \> 1.5 x ULN, AST/ALT/ALP \> 2.0 x ULN
* Female or another gender with childbearing potential not willing to adopt barrier method(s) of contraception, plus one other form, including:

  * Intrauterine system (IUS)
  * Intrauterine device (IUD)
  * Oral, injected, or implanted hormonal contraception
* Female or another gender who is lactating/breastfeeding or has a positive urine or serum pregnancy test at intake screening
* Any disorder that compromises the participant's ability to give appropriate informed consent or hinders the ability to perform the assessment and receive the study's interventions
* Any other condition not listed above that is deemed potentially harmful to the participant by the PI

Primary outcomes:
measure: Movement-Disorder Society Unified Parkinson Disease Rating Scale (MDS-UPDRS)-III
timeFrame: Day 0, 6, 12 and 18 months
measure: 10-meter Walk Test (10MWT)
timeFrame: Day 0, 6, 12 and 18 months
measure: Five Times Sit to Stand (FTSTS)
timeFrame: Day 0, 6, 12 and 18 months
measure: Mini Balance Evaluation Systems Test (Mini-BESTest)
timeFrame: Day 0, 6, 12 and 18 months
measure: The Short Parkinson's Evaluation Scale (SPES)/Scales for Outcomes in Parkinson's Disease - Motor Function (SPES/SCOPA - Motor)
timeFrame: Day 0, 6, 12 and 18 months
measure: Modified Hoehn & Yahr Scale
timeFrame: Day 0, 6, 12 and 18 months
measure: Montreal Cognitive Assessment (MoCA)
timeFrame: Day 0, 3, 6, 9, 12, 15 and 18 months
measure: Progressive Supranuclear Palsy Clinical Deficits Scale (PSP-CDS)
timeFrame: Day 0, 6, 12 and 18 months
measure: Unified Multiple System Atrophy Rating Scale (UMSARS)
timeFrame: Day 0, 6, 12 and 18 months
measure: Cortical Basal Ganglia Functional Scale (CBFS)
timeFrame: Day 0, 6, 12 and 18 months
measure: Parkinson's Disease Questionnaire - 39 (PDQ-39)
timeFrame: Day 0, 3, 6, 9, 12, 15 and 18 months
measure: The Scales for Outcomes in Parkinson's disease - Cognition (SCOPA-COG)
timeFrame: Day 0, 3, 6, 9, 12, 15 and 18 months
measure: The Scales for Outcomes in Parkinson's Disease - Autonomic Dysfunction
timeFrame: Day 0, 3, 6, 9, 12, 15 and 18 months
measure: Non-Motor Symptoms Questionnaire (NMSQ)
timeFrame: Day 0, 3, 6, 9, 12, 15 and 18 months
measure: MDS Non-Motor Rating Scale (MDS-NMS)
timeFrame: Day 0, 3, 6, 9, 12, 15 and 18 months
Secondary outcomes:
measure: Resting state brain activation pattern (fMRI analysis)
timeFrame: Day 0 and 18 months
measure: Active brain activation pattern (fMRI analysis)
timeFrame: Day 0 and 18 months
measure: Active performance accuracy and rate (fMRI analysis)
timeFrame: Day 0 and 18 months
Other outcomes:
measure: Intranasal Bone Marrow-Mesenchymal Stem Cells (BM-MSC) Indices
timeFrame: Day 0, 6 and 12 months
measure: Intravenous Bone Marrow-Mesenchymal Stem Cells (BM-MSC) Indices
timeFrame: Day 0, 6 and 12 months
measure: Bone Marrow (BM) Indices Comparative Analysis
timeFrame: Day 0, 6, 12 and 18 months
measure: Complete Blood Count (CBC) Indices Comparative Analysis
timeFrame: Day 0, 6, 12 and 18 months
measure: Epigenetics
timeFrame: Day 0 and 18 months
measure: Metagenomics - Gut Microbiota
timeFrame: Day 0 and 18 months
measure: Metagenomics - Nasopharyngeal Microbiota
timeFrame: Day 0 and 18 months
Locations:
Study officials:
affiliation: Apeiron Research Center
name: Jason Glowney, MD, MSc
role: PRINCIPAL_INVESTIGATOR
References: