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

Официальное название

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

Обзор

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.

Вмешательства

• Биопрепарат Intravenous infusion of mononuclear cells from umbilical cord blood
  When performing cell infusion, it is essential to use an infusion set and follow the standard blood transfusion procedures. Before, during, and after the infusion, monitor the patient's body temperature, pulse, breathing, and blood pressure. When infusing cells, first flush the tube with 20-30 ml of 0.9% sodium chloride, and start the infusion at a rate of 20-30 drops per minute. After half an hour, if there are no adverse reactions, increase the rate to 30-50 drops per minute. During the cell i
• Препарат Conventional medical treatment：donepezil, rivastigmine or galantamine
  The treatment is carried out using drugs such as cholinesterase inhibitors (ChEI) which are suitable for mild to moderate Alzheimer's disease. For example, donepezil, rivastigmine, galantamine, etc. The frequency and dosage of drug administration should be in accordance with the instructions provided by the drug manufacturer.The patient should maintain the stability of the medication regimen throughout the entire study period.

Первичные конечные точки

• Clinical Dementia Rating Scale-Sum of Boxes (CDR-SB) [Срок оценки: Baseline, 1st, 2nd, 3rd and 6th month after treatment]
• Activity of Daily Living Scale（ADL） [Срок оценки: Baseline, 1st, 2nd, 3rd and 6th month after treatment]

Вторичные конечные точки (6)

• Serum levels of AD markers (P-tau181, 217) [Срок оценки: Baseline, 1st, 2nd, 3rd and 6th month after treatment]
• Cerebrospinal fluid(CSF) levels of AD markers (P-tau181, 217) [Срок оценки: Baseline, 2nd month after treatment]
• Minimum Mental State Examination（MMSE）Scores [Срок оценки: Baseline, 1st, 2nd, 3rd and 6th month after treatment]
• Montreal Cognitive Assessment（MoCA） [Срок оценки: Baseline, 1st, 2nd, 3rd and 6th month after treatment]
• Alzheimer disease assessment scale-cognitive component (ADAS-Cog) [Срок оценки: Baseline, 1st, 2nd, 3rd and 6th month after treatment]
• tau-Positron Emission Tomography（tau-PET） [Срок оценки: Baseline, 3rd and 6th month after treatment]

Критерии участия

Критерии включения

• 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.

Критерии исключения

• 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.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Четверное слепое

Основная цель

Лечение

Центры проведения

Китай · 1 центр

• The First Affiliated Hospital of the University of Science and Technology of China — Хэфэй

Идентификаторы

NCT: NCT07208344 · AHSL-QLGXB-MNC-AD

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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