Intravenous Infusion of Umbilical Cord Blood as an Adjunctive Treatment for Alzheimer's Disease

A Randomized Double-blind Clinical Study on the Use of Umbilical Cord Blood as an Adjuvant Therapy to Improve Cognitive Function in Alzheimer's Disease and Its Mechanism of Action

This study is a single-center, prospective, double-blind, randomized controlled clinical trial (RCT).

Employing a parallel-group design, the trial plans to enroll 30 clinically diagnosed AD patients, who will be randomly assigned via a computerized randomization tool into three equal groups: low-dose, high-dose, and control (10 patients per group).

The blinded clinical trial consists of three phases:

**Screening Phase**: All enrolled patients must provide fully informed consent and meet inclusion criteria while avoiding exclusion criteria. Baseline assessments will be recorded, and single-cell omics samples will be collected. Patients may voluntarily opt for cerebrospinal fluid (CSF) sampling.

The umbilical cord blood (UCB) used clinically is sourced from the Shandong Cord Blood Hematopoietic Stem Cell Bank. Following erythrocyte and granulocyte depletion via lymphocyte separation and density gradient centrifugation, the UCB is purified to reduce immunogenicity and undergoes genetic screening to exclude the APOE4 risk allele.

**Treatment Phase**: In addition to standard care, patients will receive intravenous infusions at weekly intervals for four sessions. A fifth infusion will be administered one month after the fourth. The low-dose group receives 1×10⁸ UCB-derived mononuclear cells (UCB-MNCs) per infusion, the high-dose group receives 3×10⁸ UCB-MNCs, and the control group receives an equivalent volume of saline placebo.

All clinically administered UCB-MNCs undergo genetic screening to exclude the APOE4 risk allele.

**Follow-up Phase**:

Assessments will be conducted at 30 days (1 month), 60 days (2 months), 90 days (3 months), and 180 days (6 months) post-initial infusion, including:

1. CDR-SB scale scoring;
2. Total and subdomain scores of the Activities of Daily Living (ADL) scale;
3. Serum inflammatory cytokines (IL-1, IL-2, IL-6, IL-8, IL-10, TNF-α), AD biomarkers (P-tau181, P-tau217), and other relevant markers;
4. Single-cell omics sample collection;
5. Optional CSF sampling per patient preference.

After database lock, unblinding will occur for subsequent analysis.

Inclusion Criteria:

• Age range: 50 - 75 years old, gender not restricted;
• Patients diagnosed with Alzheimer's disease (AD) according to the AT(N) diagnostic framework (with positive amyloid protein PET test results);
• MMSE score between 15 and 30 points, patients with mild to moderate Alzheimer's disease;
• The patient has a fixed caregiver who is willing to accompany the patient throughout the corresponding program;
• The patient has a literacy level above primary school, sufficient to complete the tests stipulated in the program;
• The patient or the guardian consents to participate in this clinical trial voluntarily and signs the informed consent form.

Exclusion Criteria:

• Dementia caused by other diseases, such as vascular dementia, frontotemporal dementia, and Lewy body dementia, etc.;
• The patient has other major systemic diseases, malignant tumors, chronic obstructive pulmonary disease or pulmonary fibrosis, etc. related to the lungs;
• The patient's white blood cell and neutrophil levels are below the normal lower limit;
• The patient has active infectious diseases, such as syphilis, AIDS, hepatitis B, hepatitis C;
• The patient has a history of stroke, epilepsy, alcohol abuse, or abuse of psychotropic drugs;
• Severe visual or hearing impairment, or those who cannot complete the relevant assessment due to other reasons;
• Patients who have participated in other clinical trials within the last 2 months;
• Other situations that the researchers consider not suitable for participating in clinical research.