Autologous Activated Adipose-derived Stem Cells (RB-ADSC) Injected Directly Into the Brain for Mild to Moderate Alzheimer's Disease

Alzheimer Disease Clinical Trial

Official title:

Ph 1, Open-Label Safety Study of Escalating Doses of Intracerebroventricular Injections of Ex Vivo Expanded, Autologous ADSCs in Participants With Mild-Moderate AD Whose Treatment is Not Addressed Adequately by Available Therapy

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05667649
• Other study ID #: RB-ADSC-02
• Status: Recruiting
• Phase: Phase 1
• Start date: August 14, 2023
• Est. completion date: March 2025

Study information

• Verified date: February 2024
• Source: Regeneration Biomedical, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is a research study to evaluate the safety of an investigational autologous cell product obtained from participant's own adipose tissue as a possible treatment for Alzheimer disease.

Description:

This is a Phase 1, Open-Label Safety Study of Escalating Doses of Intracerebroventricular Injections of Ex Vivo Expanded, Autologous Adipose-Derived Stem Cells (ADSCs) in Participants with Mild to Moderate Alzheimer's Disease (AD) whose Treatment is not Addressed Adequately by Available Therapy (i.e., an unmet medical need). The investigational product, which is referred to as RB-ADSC, consists of stem cells obtained from the participant's own adipose tissue by lipoaspirate. After collection, the stem cells are cultured and expanded outside the body, and then reintroduced into the same patient. A soft plastic reservoir (Ommaya reservoir) is implanted under the scalp, communicating with the brain cavities (ventricles). This study will primarily evaluate the safety of RB-ADSC injected in the Ommaya reservoir in a 3 + 3 dose escalation study. The planned enrollment will be 9 participants, 3 participants per escalation Cohort. The primary objectives will evaluate adverse events, serious adverse events, and dose limiting toxicities to determine a recommended phase 2 clinical trial dose. Secondary objectives will evaluate preliminary efficacy measured by clinical assessments, volumetric MRI (Neuro Quant®), CSF biomarkers (Phospho-Tau, Total Tau, AB-42), and diagnostic imaging comparison (Amyloid PET). Each participant will be followed for 12 months after treatment.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 18
• Est. completion date: March 2025
• Est. primary completion date: February 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 45 Years to 80 Years

Eligibility

Inclusion Criteria:

• =45 and =80 years of age
• Mild to moderate AD diagnosis
• Adequate cognitive function
• Non-remarkable clinical laboratory
• Ability to voluntarily provide written informed consent
• No tumors or other disease responsible for dementia
• Well-controlled comorbidities, on stable medications for 3 months
• The participant is otherwise in good general health
• The participant must have a relative/caregiver
• Participant must be able to donate adequate amount of lipoaspirate to establish the final product
• Caregiver separately meets the specified inclusion/exclusion criteria for caregivers

Exclusion Criteria:

• Taking other medications for AD, except that donepezil memantine, AChEIs including patches, Vitamin E, fish oil, and/or gingko biloba are allowed if doses have been stable for at least 3 months prior to the Screening visit
• Stem cell implantation of any type within 3 months
• Existing ventriculoperitoneal shunts
• Neurological disorders except AD
• Psychiatric disorders including schizophrenia, bipolar/unipolar depressive disorder, delirium
• Drug or alcohol abuse or dependence within the past 5 years
• Participants with a history of cancer in the past 5 years
• No caregiver available to meet the inclusion criteria for caregivers

Related Conditions & MeSH terms

• Alzheimer Disease

Intervention

Biological:
• RB-ADSC
Ex Vivo Expanded, Autologous Adipose-Derived Stem Cells (ADSCs)

Locations

Country	Name	City	State
United States	Hoag Memorial Hospital Presbyterian	Newport Beach	California

Sponsors (1)

Lead Sponsor	Collaborator
Regeneration Biomedical, Inc.

Country where clinical trial is conducted

United States, 

References & Publications (1)

Duma C, Kopyov O, Kopyov A, Berman M, Lander E, Elam M, Arata M, Weiland D, Cannell R, Caraway C, Berman S, Scord K, Stemler L, Chung K, Khoudari S, McRory R, Duma C, Farmer S, Bravo A, Yassa C, Sanathara A, Singh E, Rapaport B. Human intracerebroventricular (ICV) injection of autologous, non-engineered, adipose-derived stromal vascular fraction (ADSVF) for neurodegenerative disorders: results of a 3-year phase 1 study of 113 injections in 31 patients. Mol Biol Rep. 2019 Oct;46(5):5257-5272. doi: 10.1007/s11033-019-04983-5. Epub 2019 Jul 20. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The safety of RB-ADSC treatment in study participants with AD	Safety will be determined by incidence, type and severity of adverse events (AE) and serious adverse events (SAE) graded according to CTCAE v5.0 and CRS revised grading system and defined by clinical relevant findings at every visit and week 28 post-treatment in physical examination, vital signs and laboratory data	up to 28 weeks
Secondary	Change from Baseline in Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-cog)	Measured by the Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-cog) is a cognitive performance test. The ADAS-cog score ranges from 0 to 70, with higher scores indicating greater cognitive impairment (higher score is worse outcome).	up to 52 weeks
Secondary	Change from Baseline in Mini Mental State Examination (MMSE)	Measured by the Mini Mental State Examination (MMSE). MMSE is a performance-based test of global cognitive status.. The MMSE score ranges from 0 to 30, with lower scores indicating greater cognitive impairment (lower score is worse outcome).	up to 52 weeks