Alzheimer's Disease Stem Cells Multiple Infusions

• ClinicalTrials.gov Identifier: NCT04040348
• Recruitment Status: Recruiting
• First Posted: July 31, 2019
• Last Update Posted: October 17, 2019
• Sponsor: Bernard (Barry) Baumel
• Information provided by (Responsible Party): Bernard (Barry) Baumel, University of Miami

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Alzheimer Disease	Biological: 100 million cells allogeneic hMSC; Biological: 200 million cells allogeneic hMSC	Phase 1

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 10 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Supportive Care
• 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
• Actual Study Start Date: October 8, 2019
• Estimated Primary Completion Date: September 1, 2021
• Estimated Study Completion Date: September 1, 2021

Arms and Interventions

Arm	Intervention/treatment
Experimental: Low Dose Cohort; The first 5 enrolled participants will receive a total of 4 intravenous infusions of 100 million cells human mesenchymal stem cells (hMSC). Participant will receive a total dose of 400 million cells of allogeneic hMSC. Infusion will be administered once every 13 weeks.	Biological: 100 million cells allogeneic hMSC; Umbilical cord-derived, allogeneic hMSC administered intravenously at a dose of 100 million cells per infusion.
Experimental: High Dose Cohort; The last 5 enrolled participants will receive a total of 4 intravenous infusions of 200 million cells human mesenchymal stem cells (hMSC). Participant will receive a total dose of 800 million cells of allogeneic hMSC. Infusion will be administered once every 13 weeks.	Biological: 200 million cells allogeneic hMSC; Umbilical cord-derived, allogeneic hMSC administered intravenously at a dose of 200 million cells per infusion.

Outcome Measures

Primary Outcome Measures :

1. 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

Secondary Outcome Measures :

1. 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.
2. 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.
3. 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.
4. 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.
5. 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.
6. 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.
7. 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.
8. 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.
9. 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.
10. Serum ApoE level over time [ Time Frame: Up to Week 65 ]
    Serum blood Apolipoprotein E (ApoE) will be evaluated in mg/dL.
11. 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.
12. Serum Tau protein level over time [ Time Frame: Up to Week 65 ]
    Serum blood Tau protein level will be evaluated in ng/L.
13. 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.
14. CSF ApoE level over time [ Time Frame: Up to Week 52 ]
    CSF Apolipoprotein E (ApoE) levels will be evaluated in mg/dL.
15. 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.
16. CSF Tau protein level over time [ Time Frame: Up to Week 52 ]
    CSF Tau protein levels will be evaluated in ng/L.
17. 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

Eligibility Criteria

• Ages Eligible for Study: 50 Years to 85 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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. Positive Amyloid Positron Emission Tomography (PET) scan
5. Meet criteria for 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 are required to have been taking cholinesterase inhibitor medications (donepezil, rivastigmine (oral or transdermal) or galantamine) on a stable dose for at least 3 months prior to Baseline Visit
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
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 within 10 years prior to Screening, unless under treatment
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:

   • Acute or sub-acute hemorrhage
   • Prior macrohemorrhage (> 1 cm in diameter)
   • > 4 microhemorrhages (< 1 cm in diameter)
   • Cortical infarct (> 1.5 cm in diameter)
   • > 1 lacunar infarct (< 1.5 cm in diameter)
   • Superficial siderosis
   • History of diffuse white matter disease defined by a score of 3 on the age-related white matter changes scale
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.

Contacts and Locations

Contacts

Contact: Carmen Perez; 305-243-0184; c.perez71@med.miami.edu

Locations

United States, Florida

University of Miami; Recruiting

Miami, Florida, United States, 33136

Contact: Carmen Perez 305-243-0184 c.perez71@med.miami.edu

Principal Investigator: Bernard (Barry) Baumel, MD

Sponsors and Collaborators

Bernard (Barry) Baumel

Investigators

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

More Information

• Responsible Party: Bernard (Barry) Baumel, Assistant Professor, University of Miami
• ClinicalTrials.gov Identifier: NCT04040348 History of Changes
• Other Study ID Numbers: 20190438
• First Posted: July 31, 2019
• Last Update Posted: October 17, 2019
• Last Verified: October 2019

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

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

Keywords provided by Bernard (Barry) Baumel, University of Miami:

Dementia; Stem cells; Alzheimer's Disease

Additional relevant MeSH terms:

Alzheimer Disease; Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases; Neurocognitive Disorders; Mental Disorders