Clinical trial NCT04040348: Alzheimer's Disease Stem Cells Multiple Infusions
Official title: A Phase I, Prospective, Open-label Trial to Evaluate the Safety, Tolerability and Exploratory Outcomes of Multiple Allogeneic Human Mesenchymal Stem Cells (HMSC) Infusions in Patients With Mild to Moderate Alzheimer's Disease
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Alzheimer Disease
Keywords: Dementia
Stem cells
Alzheimer's Disease
Lead sponsor: University of Miami
Sponsor class: OTHER
First posted: 2019-07-31
Enrollment: 6
Sex: ALL
Minimum age (years): 50
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The purpose of this research study is to test the safety, possible side effects, and possible effectiveness of mesenchymal stem cell infusions when given to people with a diagnosis of mild to moderate Alzheimer's disease.


Eligibility criteria: Inclusion Criteria:

All subjects enrolled in this trial must:

1. Provide written informed consent
2. Male or female subjects aged 50-85 years at time of signing Informed Consent
3. Mini-Mental State Examination (MMSE) between 20-26
4. Amyloid PET scan or CSF Aß1-42 positive for the presence of amyloid
5. Meet criteria for either Alzheimer's Disease or probable Alzheimer's Disease (AD) according to National Institute of Neurological and Communicative Disorders and Stroke/Alzheimer's Disease and Related Disorders Association (NINDCDS/ARDRA)
6. Subjects, if taking cholinesterase inhibitor medications (donepezil, rivastigmine (oral or transdermal) or galantamine), are required to have been taking them on a stable dose for at least 3 months prior to Baseline Visit These medicines are not required
7. Subjects already taking memantine will not have an effect in the inclusion/exclusion criteria.
8. Have a study partner
9. No clinically significant abnormal screening laboratory values, as determined by the investigator
10. Women must be postmenopausal, surgically sterile, or having infertility. A postmenopausal woman is defined as either having an intact uterus with at least 12 months of spontaneous amenorrhea or a diagnosis of menopause, defined as an Follicular Stimulating Hormone (FSH) level of \> 25 IU/L

Exclusion Criteria:

All subjects enrolled must not have:

1. Dementia other than AD
2. A negative Amyloid PET scan
3. Other neurodegenerative disease
4. Significant psychiatric illness (e.g., uncontrolled major depression, schizophrenia, bipolar affective disorder)
5. History of seizures
6. Contraindication for Magnetic Resonance Imaging (MRI)
7. History of malignancy, except:

   * \> 5 years in remission prior to screening
   * Be excised or treated basal cell, squamous carcinoma or melanoma in situ
   * Prostate cancer in situ
   * Cervical carcinoma in situ
8. Uncontrolled medical conditions

   * Hypertension
   * Diabetes
   * Unstable angina or history of Myocardial Infarction (MI) within 1 year prior to screening
   * History of alcohol or drug use disorder (except tobacco use disorder) within 2 years before the screening visit
9. Brain MRI at screening that shows evidence of findings incompatible with a diagnosis of Alzheimer's disease. Volumetric MRI scans done within 6 months prior to ICF signature will be accepted if completed locally.
10. History of bleeding disorder
11. History of or positive results for Human Immunodeficiency Virus (HIV)
12. History of or positive results for Hepatitis C Virus (HCV) or Hepatitis B Virus (HBV)
13. Hypersensitivity to dimethyl sulfoxide (DMSO)
14. Inability to perform any of the assessments required for endpoint analysis
15. Currently receiving (or received within four weeks of screening) experimental agents for the treatment of AD or enrolled in clinical trials in the prior 3 months
16. Be a transplant recipient, or on active listing (or expected future listing) for transplant of any organ.
17. Any other condition that, in the opinion of the investigator, may compromise the safety or compliance of the patient or preclude successful completion of the study.

Primary outcomes:
measure: Number of Incidence of any Treatment-Emergent Serious Adverse Events (TE-SAEs)
timeFrame: One month post-infusion
Secondary outcomes:
measure: Cognitive function over time as assessed by the Alzheimer's Disease Assessment Scale - Cognitive (ADAS-Cog 11)
timeFrame: Up to Week 65
measure: Cognitive function over time as assessed by the Mini Mental State Examination (MMSE) of Folstein test
timeFrame: Up to Week 65
measure: Depressive symptoms over time as assessed by the Geriatric Depression Scale (GDS) Short Version
timeFrame: Up to Week 65
measure: Participant quality of life over time assessed via Alzheimer's Disease Related Quality of Life (ADRQL-40) Questionnaire as completed by the caregiver
timeFrame: Up to Week 65
measure: Participant quality of life over time as assessed via the Alzheimer's Disease Cooperative Study Activities of Daily Living (ADCS-ADL) Questionnaire as completed by the caregiver
timeFrame: Up to Week 65
measure: Neuropsychiatric Inventory-Q (NPI-Q) Scores over time
timeFrame: Up to Week 52
measure: Caregiver's Quality of life over time as assessed by the Caregiver Self-Assessment Questionnaire scores
timeFrame: Up to Week 52
measure: Biomarker levels over time
timeFrame: Up to Week 65
measure: Serum ApoE level over time
timeFrame: Up to Week 65
measure: Serum PRA level over time
timeFrame: Up to Week 65
measure: Serum Tau protein level over time
timeFrame: Up to Week 65
measure: Cerebrospinal Fluid (CSF) Biomarker levels over time
timeFrame: Up to Week 52
measure: CSF ApoE level over time
timeFrame: Up to Week 52
measure: CSF PRA level over time
timeFrame: Up to Week 52
measure: CSF Tau protein level over time
timeFrame: Up to Week 52
measure: Change in hippocampal volume
timeFrame: Baseline to Week 6, Baseline to Week 52
Other outcomes:
Locations:
city: Miami
country: United States
facility: University of Miami
state: Florida
Study officials:
affiliation: University of Miami
name: Bernard (Barry) Baumel, MD
role: PRINCIPAL_INVESTIGATOR
References: