Alzheimer's Disease Stem Cells Multiple Infusions

• ClinicalTrials.gov Identifier: NCT04040348
• Recruitment Status: Active, not recruiting
• First Posted: July 31, 2019
• Last Update Posted: May 3, 2023
• Sponsor: Bernard (Barry) Baumel
• Information provided by (Responsible Party): Bernard (Barry) Baumel, University of Miami

Tracking Information

• First Submitted Date: July 30, 2019
• First Posted Date: July 31, 2019
• Last Update Posted Date: May 3, 2023
• Actual Study Start Date: October 8, 2019
• Actual Primary Completion Date: May 1, 2023 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: July 30, 2019)

Number of Incidence of any Treatment-Emergent Serious Adverse Events (TE-SAEs) [ Time Frame: One month post-infusion ]

All adverse events will be evaluated by the investigator for relationship with the study intervention. Treatment-Emergent Serious Adverse Events is defined as any untoward medical occurrence with a reasonable possibility that it is caused by the study intervention that:

• Is life-threatening (e.g.; leads to stroke or non-fatal pulmonary embolism);
• Requires inpatient hospitalization or prolongation of existing hospitalization;
• Results in persistent or significant disability/incapacity
• Results in other clinically significant sign(s) or symptom(s), (e.g.; clinically asymptomatic brain microhemorrhages); or
• Results in death

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: July 13, 2021)

• Cognitive function over time as assessed by the Alzheimer's Disease Assessment Scale - Cognitive (ADAS-Cog 11) [ Time Frame: Up to Week 65 ]
  The ADAS-Cog 11 is a 13-item version of ADAS-Cog comprising of the original 11-item ADAS-Cog as well as Delayed Recall and Digit Cancellation items. The total score ranges from 0-85 points, with a lower score indicating better performance.
• Cognitive function over time as assessed by the Mini Mental State Examination (MMSE) of Folstein test [ Time Frame: Up to Week 65 ]
  The MMSE assesses orientation to time and place, immediate and delayed recall of words, attention and calculation, language (naming, comprehension and repetition), and spatial ability (copying a figure). The total score ranges from 0-30, with a higher score indicating better cognitive performance.
• Depressive symptoms over time as assessed by the Geriatric Depression Scale (GDS) Short Version [ Time Frame: Up to Week 65 ]
  The GDS is a 15-item questionnaire with each item counting as one point. The total score ranges from 0 to 15 with a score greater than 5 indicating possible depression.
• Participant quality of life over time assessed via Alzheimer's Disease Related Quality of Life (ADRQL-40) Questionnaire as completed by the caregiver [ Time Frame: Up to Week 65 ]
  ADRQL-40 is a questionnaire completed by the caregiver assessing the quality of life of the participant with AD. The total score for the ADRQL is computed by summing the values assigned to the responses, dividing the sum by the maximum value for the scale and multiplying the results by 100 to obtain a percentage score of 0 to 100. A higher score reflects a higher quality of life.
• 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 [ Time Frame: Up to Week 65 ]
  The ADCS-ADL is a 23 item questionnaire completed by the caregiver assessing the basic and instrumental activities of daily living by the AD participant. Total score range from 0-78 with the higher score indicating increased independence.
• Neuropsychiatric Inventory-Q (NPI-Q) Scores over time [ Time Frame: Up to Week 52 ]
  The NPI-Q is a questionnaire used to assess behavioral changes common in dementia patients. This questionnaire is completed by the caregiver. The questionnaire consists of 12 items with each item having a scoring range between 0-3. The higher score indicates a more severe neuropsychiatric symptomatology.
• Caregiver's Quality of life over time as assessed by the Caregiver Self-Assessment Questionnaire scores [ Time Frame: Up to Week 52 ]
  The Caregiver Self-Assessment questionnaire is completed by the caregiver. It is an 18-item questionnaire answered with a "yes" or "no". Evidence of distress is indicated for having over 10 "yes" answers.
• Biomarker levels over time [ Time Frame: Up to Week 65 ]
  Serum blood inflammatory and biomarker levels will be evaluated including Interleukin-6 (IL-6), Neurofilament light (NfL), Amyloid Beta 40 (Aβ40) and Amyloid Beta 42 (Aβ42) in pg/mL.
• Serum ApoE level over time [ Time Frame: Up to Week 65 ]
  Serum blood Apolipoprotein E (ApoE) will be evaluated in mg/dL.
• Serum PRA level over time [ Time Frame: Up to Week 65 ]
  Serum blood Plasma Renin Activity (PRA) will be evaluated in ng/mL per hour.
• Serum Tau protein level over time [ Time Frame: Up to Week 65 ]
  Serum blood Tau protein level will be evaluated in ng/L.
• Cerebrospinal Fluid (CSF) Biomarker levels over time [ Time Frame: Up to Week 52 ]
  CSF inflammatory and biomarker levels will be evaluated including Interleukin-6 (IL-6), Neurofilament light (NfL), Amyloid Beta 40 (Aβ40) and Amyloid Beta 42 (Aβ42) in pg/mL.
• CSF ApoE level over time [ Time Frame: Up to Week 52 ]
  CSF Apolipoprotein E (ApoE) levels will be evaluated in mg/dL.
• CSF PRA level over time [ Time Frame: Up to Week 52 ]
  CSF Plasma Renin Activity (PRA) levels will be evaluated in ng/mL per hour.
• CSF Tau protein level over time [ Time Frame: Up to Week 52 ]
  CSF Tau protein levels will be evaluated in ng/L.
• Change in hippocampal volume [ Time Frame: Baseline to Week 6, Baseline to Week 52 ]
  Change in hippocampal volume will be assessed via MRI Brain volumetric studies

Original Secondary Outcome Measures (submitted: July 30, 2019)

• Cognitive function over time as assessed by the Alzheimer's Disease Assessment Scale - Cognitive (ADAS-Cog 11) [ Time Frame: Up to Week 65 ]
  The ADAS-Cog 11 is a 13-item version of ADAS-Cog comprising of the original 11-item ADAS-Cog as well as Delayed Recall and Digit Cancellation items. The total score ranges from 0-85 points, with a lower score indicating better performance.
• Cognitive function over time as assessed by the Mini Mental State Examination (MMSE) of Folstein test [ Time Frame: Up to Week 65 ]
  The MMSE assesses orientation to time and place, immediate and delayed recall of words, attention and calculation, language (naming, comprehension and repetition), and spatial ability (copying a figure). The total score ranges from 0-30, with a higher score indicating better cognitive performance.
• Depressive symptoms over time as assessed by the Geriatric Depression Scale (GDS) Short Version [ Time Frame: Up to Week 65 ]
  The GDS is a 15-item questionnaire with each item counting as one point. The total score ranges from 0 to 15 with a score greater than 5 indicating possible depression.
• Olfactory function over time as assessed by the Odor Identification test. [ Time Frame: Up to Week 65 ]
  Olfactory function is assessed via a self-administered 16-item odor identification test that provides an indication of anosmia (mild, moderate, or severe), and an index to detect malingering. Total scores range from 0-16 with the higher score indicating higher smell function.
• Participant quality of life over time assessed via Alzheimer's Disease Related Quality of Life (ADRQL-40) Questionnaire as completed by the caregiver [ Time Frame: Up to Week 65 ]
  ADRQL-40 is a questionnaire completed by the caregiver assessing the quality of life of the participant with AD. The total score for the ADRQL is computed by summing the values assigned to the responses, dividing the sum by the maximum value for the scale and multiplying the results by 100 to obtain a percentage score of 0 to 100. A higher score reflects a higher quality of life.
• 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 [ Time Frame: Up to Week 65 ]
  The ADCS-ADL is a 23 item questionnaire completed by the caregiver assessing the basic and instrumental activities of daily living by the AD participant. Total score range from 0-78 with the higher score indicating increased independence.
• Neuropsychiatric Inventory-Q (NPI-Q) Scores over time [ Time Frame: Up to Week 52 ]
  The NPI-Q is a questionnaire used to assess behavioral changes common in dementia patients. This questionnaire is completed by the caregiver. The questionnaire consists of 12 items with each item having a scoring range between 0-3. The higher score indicates a more severe neuropsychiatric symptomatology.
• Caregiver's Quality of life over time as assessed by the Caregiver Self-Assessment Questionnaire scores [ Time Frame: Up to Week 52 ]
  The Caregiver Self-Assessment questionnaire is completed by the caregiver. It is an 18-item questionnaire answered with a "yes" or "no". Evidence of distress is indicated for having over 10 "yes" answers.
• Serum Biomarker levels over time [ Time Frame: Up to Week 65 ]
  Serum blood inflammatory and biomarker levels will be evaluated including Interleukin-6 (IL-6), Apolipoprotein E (ApoE), Plasma renin activity (PRA), Neurofilament light (NfL), Amyloid Beta 40 (Aβ40), Amyloid Beta 42 (Aβ42), and Tau protein.
• Cerebrospinal Fluid (CSF) Biomarker levels over time [ Time Frame: Up to Week 52 ]
  CSF inflammatory and biomarker levels will be evaluated including Interleukin-6 (IL-6), Neurofilament light (NfL), Amyloid Beta 40 (Aβ40), Amyloid Beta 42 (Aβ42), Tau protein and phosphorylated Tau (p-Tau) protein.
• Change in hippocampal volume [ Time Frame: Baseline to Week 6, Baseline to Week 52 ]
  Change in hippocampal volume will be assessed via MRI Brain volumetric studies

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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
• 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.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 1
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Alzheimer Disease

Intervention

Biological: Approximately 100 million cells allogeneic hMSC

Umbilical cord-derived, allogeneic hMSC administered intravenously at a dose of approximately 100 million cells per infusion.

Study Arms

Experimental: hMSC Treatment group

Participants in the hMSC treatment group will receive a total of 4 doses of the hMSC intervention. Each dose will be administered once about every 13 weeks within a year period.

Intervention: Biological: Approximately 100 million cells allogeneic hMSC

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Active, not recruiting
• Estimated Enrollment (submitted: May 18, 2020): 6
• Original Estimated Enrollment (submitted: July 30, 2019): 10
• Estimated Study Completion Date: August 1, 2023
• Actual Primary Completion Date: May 1, 2023 (Final data collection date for primary outcome measure)

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 50 Years to 85 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT04040348
• Other Study ID Numbers: 20190438
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Bernard (Barry) Baumel, University of Miami
• Original Responsible Party: Same as current
• Current Study Sponsor: Bernard (Barry) Baumel
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Principal Investigator: Bernard (Barry) Baumel, MD; University of Miami

• PRS Account: University of Miami
• Verification Date: May 2023