Standard Optimization of Stem Cells in Parkinson's Disease and Atypical Parkinsonism

NCT06858254 | Not Yet Recruiting Phase 1 FDA Drug

• 1 other identifier: ARC-PD-PPS-01
• Study Type: interventional
• Target: 60
• Locations: 0 countries
• Sites: N/A

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.

Conditions

Atypical Parkinsonism; Parkinson Disease (PD)

Keywords

Atypical Parkinsonism; Parkinson-Plus Syndrome; Stem Cells; MSCs; Epigenetics; Metagenomics; Parkinson's Disease

Outcome Measures

Primary Outcomes (15)

• Movement-Disorder Society Unified Parkinson Disease Rating Scale (MDS-UPDRS)-III

  The MDS-UPDRS is the most widely used clinical rating scale for Parkinson disease. Part III is a motor examination (33 scores summed from 18 questions) conducted by the rater. Total scores can range from 0 to 141, with higher scores indicating worse disease severity.

  Day 0, 6, 12 and 18 months

• 10-meter Walk Test (10MWT)

  The 10MWT is an assessment of gait speed over a short distance (2 meters ramp up, 6 meters walking, 2 meters ramp down). The aforementioned distances will be pre-measured for accuracy and only the middle 6 meters will be timed. Participants will be asked to walk at a comfortable pace for 2 trials and a fast pace for 2 trials.

  Day 0, 6, 12 and 18 months

• Five Times Sit to Stand (FTSTS)

  The FTSTS objectively assesses the time it takes to complete 5 sit-to-stands and is a method to observe movement strategies or compensations. The test will be performed in a standard chair with participants instructed to stand up and sit down 5 times as quickly as possible.

  Day 0, 6, 12 and 18 months

• Mini Balance Evaluation Systems Test (Mini-BESTest)

  The Mini-BESTest aims to target 6 different balance control systems. The measure includes 14 items assessing anticipatory postural adjustments, reactive balance control, sensory orientation, and dynamic gait. This is scored on a 3-item ordinal scale resulting in a maximum score of 28.

  Day 0, 6, 12 and 18 months

• The Short Parkinson's Evaluation Scale (SPES)/Scales for Outcomes in Parkinson's Disease - Motor Function (SPES/SCOPA - Motor)

  The SPES/Scales for Outcomes in Parkinson's will be used to evaluate motor function and includes 3 sections: Motor evaluation (10 items, maximum of 42 points), Activities of Daily Living (7 items, maximum 21 points), and Motor complications (4 items, maximum 12 points - with 2 items on motor fluctuation \[6 points\] and 2 on dyskinesias \[6 points\]). Response options for all items range 0 to 3.

  Day 0, 6, 12 and 18 months

• Modified Hoehn & Yahr Scale

  The Modified Hoehn and Yahr Scale contains additional criteria to rate Parkinson disease symptoms on a scale of 1-5. Higher scores indicate increased disease progression.

  Day 0, 6, 12 and 18 months

• Montreal Cognitive Assessment (MoCA)

  The MoCA is a rapid screen of cognitive abilities to detect mild cognitive dysfunction. Participants are tested on 16 items that cover multiple cognitive domains. The score ranges from 0-30, with higher scores indicating less cognitive impairment.

  Day 0, 3, 6, 9, 12, 15 and 18 months

• Progressive Supranuclear Palsy Clinical Deficits Scale (PSP-CDS)

  The PSP-CDS was developed to assess clinical deficits in patients with Progressive Supranuclear Palsy (PSP). The scale measures severity of deficits in seven patient-related clinical domains: Akinesia-rigidity, Bradyphrenia, Communication, Dysphagia, Eye movements, Finger dexterity, and Gait \& balance; each scored from 0 to 3. The sum of the individual domains provides a total score ranging from 0 (no deficit in any domain) to 21 (severe deficit in all domains) with higher scores representing a worse outcome.

  Day 0, 6, 12 and 18 months

• Unified Multiple System Atrophy Rating Scale (UMSARS)

  The UMSARS will be used as a clinical rating scale to provide measures of disease progression in multiple systems atrophy. It is composed of four subscales: UMSARS-I (historical review of disease-related impairments, 12 items, scored 0 to 4), UMSARS-II (motor examination, 14 items, scored 0 to 4), UMSARS-III (autonomic examination - records blood pressure and heart rate in the supine and standing positions), and UMSARS-IV (global disability scale - rates chore-based disability, 1 item, ranges from 1 to 5). Higher scores on the UMSARS indicate greater disability.

  Day 0, 6, 12 and 18 months

• Cortical Basal Ganglia Functional Scale (CBFS)

  The CBFS is a rating scale that evaluates experiences in daily living (EDLs), behavioral, language, and cognitive impairments in patients with 4 repeat tauopathies (4RTs). The CBFS consists of 14 questions on Motor EDLs and 17 questions on Non-motor EDLs, each of which are rated on a Likert scale rating function from 0 to 4, where 0 = Normal or No problems and 4 = Severe problems. The questions are for the patient, but should be answered by both the patient and their caregiver together.

  Day 0, 6, 12 and 18 months

• Parkinson's Disease Questionnaire - 39 (PDQ-39)

  The PDQ-39 is a self report questionnaire that assesses quality of life over the past month across 8 different dimensions (Activities of daily living, Attention and working memory, Cognition, Communication, Depression, Functional mobility, Quality of life, Social relationships, Social relationships, Social support). Items are scored based on a 5-point ordinal system with lower scores reflecting better quality of life. Each dimension total score ranges from 0 (never having difficulty) to 100 (always having difficulty) with lower scores being a better outcome.

  Day 0, 3, 6, 9, 12, 15 and 18 months

• The Scales for Outcomes in Parkinson's disease - Cognition (SCOPA-COG)

  The SCOPA-COG consists of 10 items divided over four domains: memory (4 items), attention (2 items), executive function (3 items), and visuospatial function (1 item). Scores range from 0-43, with higher scores reflecting better performance.

  Day 0, 3, 6, 9, 12, 15 and 18 months

• The Scales for Outcomes in Parkinson's Disease - Autonomic Dysfunction

  The SCOPA-AUT is self-completed by patients and consists of 23 items assessing the following domains: Gastrointestinal (7 items), Urinary (6 items), Cardiovascular (3 items), Thermoregulatory (4 items), Pupillomotor (1 item), and Sexual (2 items female, 2 items male). The maximum score is 69, with the score for each item ranging from 0 (never experiencing the symptom) to 3 (often experiencing the symptom).

  Day 0, 3, 6, 9, 12, 15 and 18 months

• Non-Motor Symptoms Questionnaire (NMSQ)

  The NMSQ is a comprehensive assessment of a diverse range of non-motor symptoms which can occur in all stages of Parkinson's disease. It is a patient-based screening tool designed to draw attention to the presence of non-motor symptoms in patients. Responses are marked as "yes" or "no" in regard to symptoms over the past month.

  Day 0, 3, 6, 9, 12, 15 and 18 months

• MDS Non-Motor Rating Scale (MDS-NMS)

  The MDS-NMS is a rater completed assessment that measures frequency and severity of 13 non-motor domains, over 52 items and covers a range of key non-motor symptoms both PD and treatment related. Scores are rated based on symptoms over the past month on frequency (scale from 0 to 4) and severity (scale 0 to 4), with higher scores reflecting more frequent and severe symptoms.

  Day 0, 3, 6, 9, 12, 15 and 18 months

Secondary Outcomes (3)

• Resting state brain activation pattern (fMRI analysis)

  Day 0 and 18 months

• Active brain activation pattern (fMRI analysis)

  Day 0 and 18 months

• Active performance accuracy and rate (fMRI analysis)

  Day 0 and 18 months

Other Outcomes (7)

• Intranasal Bone Marrow-Mesenchymal Stem Cells (BM-MSC) Indices

  Day 0, 6 and 12 months

• Intravenous Bone Marrow-Mesenchymal Stem Cells (BM-MSC) Indices

  Day 0, 6 and 12 months

• Bone Marrow (BM) Indices Comparative Analysis

  Day 0, 6, 12 and 18 months

Study Arms (4)

Parkinson Disease Group 1

EXPERIMENTAL

Day 0 - Sham IV + INA BMAC 6 months - IV BMA + Sham INA 12 months - IV BMA + INA BMAC

Biological: Autologous mesenchymal stem cells

Parkinson Plus Syndrome Group 1

EXPERIMENTAL

Day 0 - Sham IV + INA BMAC 6 months - IV BMA + Sham INA 12 months - IV BMA + INA BMAC

Biological: Autologous mesenchymal stem cells

Parkinson Disease Group 2

EXPERIMENTAL

Day 0 - IV BMA + Sham INA 6 months - Sham IV + INA BMAC 12 months - IV BMA + INA BMAC

Biological: Autologous mesenchymal stem cells

Parkinson Plus Syndrome Group 2

EXPERIMENTAL

Day 0 - IV BMA + Sham INA 6 months - Sham IV + INA BMAC 12 months - IV BMA + INA BMAC

Biological: Autologous mesenchymal stem cells

Interventions

Autologous mesenchymal stem cells BIOLOGICAL

1. Participant's blood is drawn at the start of each visit. 2. Bone marrow aspirate is drawn from the posterior aspect of the pelvis and is subsequently harvested and processed. 3. The following procedures are administered in a crossover design (Day 0 and 6 months): * Intranasal bone marrow aspirate administration (INA BMAC) OR Sham INA * Intravenous bone marrow aspirate administration (IV BMA) OR Sham IVA 4. At 12 months, all participants receive IV BMA + INA BMAC

Parkinson Disease Group 1; Parkinson Disease Group 2; Parkinson Plus Syndrome Group 1; Parkinson Plus Syndrome Group 2

Eligibility Criteria

• Age: 40 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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
• DLB -
• High probability of cognitive capacity to give informed consent by the Montreal Cognitive Assessment (MoCA), with a value \>/= 23

You may not qualify if:

• 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)

Sponsors & Collaborators

• Apeiron Research Center: lead
• University of Colorado, Boulder: collaborator

MeSH Terms

Conditions

Parkinson Disease

Condition Hierarchy (Ancestors)

Parkinsonian Disorders; Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases

Study Officials

• Jason Glowney, MD, MSc

  Apeiron Research Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Jenna Zajac, PT, DPT, PhD

CONTACT

720-593-7595; jzajac@apeironresearch.org

Robert Pickels, MS

CONTACT

720-583-5047; rpickels@apeironresearch.org

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator/Medical Director

Study Record Dates

• First Submitted: February 19, 2025
• First Posted: March 5, 2025
• Study Start: April 1, 2025
• Primary Completion (Estimated): April 1, 2028
• Study Completion (Estimated): April 1, 2028
• Last Updated: March 5, 2025

Record last verified: 2025-02

Data Sharing

• IPD Sharing: Will not share