Clinical trial NCT06775964: Stem Cell Therapy for Early Alzheimer's Disease
Official title: Mesenchymal Stem Cell Therapy for Early Alzheimer's Disease
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Cognitive Dysfunction
Keywords: Mild Cognitive Impairment
Cognitive Decline
Alzheimer's disease
Lead sponsor: The University of Texas Health Science Center, Houston
Sponsor class: OTHER
Collaborators: name: Weston Brain Institute
First posted: 2025-01-15
Enrollment: 12
Sex: ALL
Minimum age (years): 60
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: This is a Phase 1b/2a open label study to assess the safety and tolerability, as well as reduction of neuroinflammation after four IV-infusions of autologous, adipose-derived, Mesenchymal Stem Cells (adMSCs) over a 13-week treatment period in 12 subjects who are clinically diagnosed with late pre-symptomatic or prodromal AD, exhibit an Alzheimer's pathology and peripheral inflammatory profile.
Primary purpose: TREATMENT

Brief summary: The goal of this clinical trial is to learn if stem cell therapy works to treat brain inflammation in adults. Inflammation in the brain may be involved in adults who have memory or thinking problems. The stem cells will be taken from participant's fat samples, processed and given back to participants, so they are their own donor. The main questions this trial aims to answer are:

* Does stem cell therapy reduce inflammation in the brain?
* Does stem cell therapy improve brain activity?
* Does stem cell therapy slow down progression to Alzheimer's disease?

Participants will:

* Have a small fat biopsy taken at a doctor's office to process stem cells
* Receive 4 infusions of stem cells, through a vein in the arm over 12 weeks
* Visit the clinic every 2-4 weeks for the first 4 months and then every 1-2 months for 8 months for checkups and tests

Detailed description: This is a Phase 1b/2a open label study to assess the safety and tolerability, as well as reduction of neuroinflammation after four IV-infusions of autologous, adipose-derived, Mesenchymal Stem Cells (adMSCs) over a 13-week treatment period in 12 subjects who are clinically diagnosed with late pre-symptomatic or prodromal AD, exhibit an Alzheimer's pathology and peripheral inflammatory profile.

To date, most drugs for AD primarily treat symptoms. Moreover, several anti-amyloid antibodies have reduced amyloid burden, but have only modestly affected cognitive progression, suggesting that other pathways are also important for AD progression. Neuroinflammation may be important for AD progression. The discovery of increased levels of inflammatory markers in patients at different clinical stages of AD, and the iden-tification of AD risk genes associated with innate immune functions, suggest that neuroinflammation may affect AD pathogenesis, making it an optimal candidate for targeted therapy to reduce disease progression. In this study, we aim to treat neuroinflammation with autologous adMSCs. These cells may represent a superior therapeutic alternative for AD be-cause they exhibit multi-therapeutic effects, including anti-inflammatory properties, reduced amyloid-β activity, and neurogenesis, which collec-tively, may reduce disease progression and improve brain activity. In addition, autologous adMSCs demonstrate low immunogenicity, which limits Graft Versus Host Disease (GVHD) during cell administration. Furthermore, our preclinical and clinical studies with adMSCs have shown that they are safe and effective at reducing inflammation and improving cognitive outcomes. A positive outcome would result in a paradigm shift in the treatment of AD that could potentially be a standard of care.

Eligibility criteria: Inclusion Criteria:

1. Has signed an informed consent form before any assessment is performed as part of the study.
2. Be male or female between 60 and 80 years old.
3. Subject has been or is in process of being clinically diagnosed with late pre-symptomatic or mild cognitive impairment (MCI) due to AD (prodromal AD).
4. Mini-Mental State Examination (MMSE) score of ≥ 22
5. Has an MRI to evaluate AD pathology (may use previous if within 6mo.)
6. Has APOE status to evaluate AD pathology (may use previous result)
7. Proficiency in English is required because cognitive tests are administered in English only.
8. Has evidence of brain amyloidosis via PET Scan or Aβ42/40 ratios in CSF.
9. Has evidence of peripheral inflammatory profile based on CRP (≥ 8 mg/L), IL-6 (≥ 3.1 pg/mL), TNF-α (10 pg/mL), or erythrocyte sedimentation rate (ESR) (≥20 mm/h) in blood assays.
10. Is in the opinion of the Investigator, in good general medical health based upon medical history, physical examination, laboratory tests, vital signs and EKG.

Exclusion Criteria:

1. Current medical or neurological condition that might impact cognition or performance on cognitive assessments. (e.g., traumatic brain injury (TBI), Parkinson's disease (PD), multiple sclerosis, etc.)
2. Inability or unwillingness of patient to undergo neuropsychological testing.
3. Advanced, severe, progressive or unstable disease that may interfere with the safety, tolerability and study assessments, or put the subject at special risk. (e.g., significant cardiac disease, severe renal impairment, severe hepatic impairment, autoimmune disease, etc.)
4. History of malignancy of any organ system within the past 60 months, that in the opinion of the investigator would impede evaluation or interpretation of subject safety or study results.
5. Females of childbearing potential must not be pregnant.
6. Inability or unwillingness to undergo PET Scans.
7. Inability or unwillingness to undergo MRI Scans.
8. Positive blood test for either HIV, Hepatitis B, Hepatitis C or Syphilis
9. Positive for TSPO SNP rs6971
10. Inability or unwillingness to undergo Lumbar Punctures.
11. Inability or unwillingness to undergo infusions.
12. Any condition, which in the opinion of the investigator, would put the subject at undue risk or would interfere with evaluation of the investigational product or interpretation of subject safety or study results.

Primary outcomes:
measure: Change in TSPO levels, measured by the PET scan, from baseline to midpoint and baseline to end of study
timeFrame: Baseline, midpoint (169 days from 1st infusion)
measure: Inflammatory cytokines in CSF following adMSC therapy
timeFrame: Baseline, midpoint (169 days from 1st infusion)
Secondary outcomes:
measure: Number of participants with treatment-related adverse events
timeFrame: Baseline - End of Study (337 days from 1st infusion)
measure: Changes in neurofilament light chain (Nf-L) in CSF following adMSC therapy
timeFrame: Baseline, midpoint (169 days from 1st infusion)
measure: Changes in Glial fibrillary acidic protein (GFAP) in CSF following adMSC therapy
timeFrame: Baseline, midpoint (169 days from 1st infusion)
measure: Changes in Total Tau/phosphor-Tau ratios in CSF following adMSC therapy
timeFrame: Baseline, midpoint (169 days from 1st infusion)
measure: Changes in cerebral metabolism activity via FDG PET imaging from image baseline to midpoint
timeFrame: Baseline, midpoint (169 days from 1st infusion)
measure: Changes in amyloid-β 42/40 ratio in CSF following adMSC therapy
timeFrame: Baseline, midpoint (169 days from 1st infusion)
measure: Change in Mini-Mental Status Examination (MMSE) following adMSC therapy
timeFrame: Baseline, End of Study (337 days from 1st infusion)
measure: Change in Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) scores following adMSC therapy
timeFrame: Baseline, End of Study (337 days from 1st infusion)
measure: Change in instrumental activities of daily living via Lawton IADL Scale scores following adMSC therapy
timeFrame: Baseline, End of Study (337 days from 1st infusion)
measure: Measure immune pathway marker level changes in blood from screening/baseline to midpoint (D1-D169) and from screening/baseline to end of study (D1-D337)
timeFrame: Baseline, midpoint (169 days from 1st infusion), End of Study (337 days from 1st infusion)
measure: Measure immune pathway marker level changes from screening/baseline to midpoint (D1-D169) in CSF
timeFrame: Baseline, midpoint (169 days from 1st infusion)
Other outcomes:
Locations:
city: Houston
country: United States
facility: The University of Texas Health Science Center at Houston (UTHealth)
state: Texas
Study officials:
affiliation: The University of Texas Health Science Center, Houston
name: Paul E Schulz, MD
role: PRINCIPAL_INVESTIGATOR
References: