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
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- 入组人数
- 30
- 试验地点
- 1
- 主要终点
- Clinical Dementia Rating Scale-Sum of Boxes (CDR-SB)
研究概览
简要总结
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:
- CDR-SB scale scoring;
- Total and subdomain scores of the Activities of Daily Living (ADL) scale;
- 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;
- Single-cell omics sample collection;
- Optional CSF sampling per patient preference.
After database lock, unblinding will occur for subsequent analysis.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 50 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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.
研究组 & 干预措施
Control group
The conventional treatment plan was supplemented with intravenous injection of normal saline (in a blinded manner)
干预措施: Conventional medical treatment：donepezil, rivastigmine or galantamine (Drug)
Low-dose group
In addition to the conventional treatment regimen, intravenous infusion of umbilical cord blood mononuclear cells (1×10^8 cells per infusion) will be administered. The infusions will be carried out via the intravenous route at one - week intervals for a total of four consecutive times. One month after the completion of the fourth infusion, the fifth infusion will be performed.
干预措施: Intravenous infusion of mononuclear cells from umbilical cord blood (Biological)
Low-dose group
In addition to the conventional treatment regimen, intravenous infusion of umbilical cord blood mononuclear cells (1×10^8 cells per infusion) will be administered. The infusions will be carried out via the intravenous route at one - week intervals for a total of four consecutive times. One month after the completion of the fourth infusion, the fifth infusion will be performed.
干预措施: Conventional medical treatment：donepezil, rivastigmine or galantamine (Drug)
High-dose group
In addition to the conventional treatment regimen, intravenous infusion of umbilical cord blood mononuclear cells (3×10^8 cells per infusion) will be administered. The infusions will be carried out via the intravenous route at one - week intervals for a total of four consecutive times. One month after the completion of the fourth infusion, the fifth infusion will be performed.
干预措施: Intravenous infusion of mononuclear cells from umbilical cord blood (Biological)
High-dose group
In addition to the conventional treatment regimen, intravenous infusion of umbilical cord blood mononuclear cells (3×10^8 cells per infusion) will be administered. The infusions will be carried out via the intravenous route at one - week intervals for a total of four consecutive times. One month after the completion of the fourth infusion, the fifth infusion will be performed.
干预措施: Conventional medical treatment：donepezil, rivastigmine or galantamine (Drug)
结局指标
主要结局
Clinical Dementia Rating Scale-Sum of Boxes (CDR-SB)
时间窗: Baseline, 1st, 2nd, 3rd and 6th month after treatment
The Clinical Dementia Rating Scale-Sum of Boxes (CDR-SB) assesses cognitive functions through six different sub-items, including memory, orientation, judgment and problem-solving ability, social skills, family life and hobbies, and self-care ability. The total score of CDR-SB ranges from 0 to 18. The higher the score, the worse the patient's cognitive function and daily living ability. This helps to provide a more comprehensive understanding of the patient's cognitive functions in all aspects. The assessors need to undergo professional training, be familiar with the assessment methods and scoring criteria, and avoid being influenced by subjective factors in the assessment results. During the assessment process, it is necessary to have adequate communication with the respondents and caregivers to understand the medical history and living conditions, in order to obtain more accurate information.
Activity of Daily Living Scale（ADL）
时间窗: Baseline, 1st, 2nd, 3rd and 6th month after treatment
Activity of Daily Living Scale（ADL） is commonly used to assess the daily living abilities of the elderly, and it plays a crucial role in the screening of Alzheimer's disease (AD) and mild cognitive impairment (MCI). The minimum score is 16 (which is completely normal). Scores above 16 indicate varying degrees of functional decline, with the maximum being 56. The ADL scale consists of 14 items and is divided into two parts: the first part is the self-care scale for physical activities, including activities such as using the toilet, eating, dressing, daily hygiene, walking, and bathing. The second part is the instrumental daily living ability scale, including activities such as making phone calls, shopping, cooking, housework, taking public transportation, taking medicine, and managing finances.
次要结局
- Serum levels of AD markers (P-tau181, 217)(Baseline, 1st, 2nd, 3rd and 6th month after treatment)
- Cerebrospinal fluid(CSF) levels of AD markers (P-tau181, 217)(Baseline, 2nd month after treatment)
- Minimum Mental State Examination（MMSE）Scores(Baseline, 1st, 2nd, 3rd and 6th month after treatment)
- Montreal Cognitive Assessment（MoCA）(Baseline, 1st, 2nd, 3rd and 6th month after treatment)
- Alzheimer disease assessment scale-cognitive component (ADAS-Cog)(Baseline, 1st, 2nd, 3rd and 6th month after treatment)
- tau-Positron Emission Tomography（tau-PET）(Baseline, 3rd and 6th month after treatment)