The Clinical Study of Synaptic Plasticity-based Lencanumab for the Treatment of Early Alzheimer's Disease
Trial statusRecruiting
Trial phaseNot listed
Trial typeObservational
Biological sexAll
Age50-90
SponsorCuibai Wei，Clinical Professor
About this trial
Alzheimer's disease (AD) manifests itself in cognitive decline, impaired ability to perform daily life, and a variety of behavioral and psychiatric symptoms, seriously endangering the health of the elderly. The prevalence and disability rates of AD in China remain high, and the lack of effective treatment options has brought a heavy burden to patients and their families. Early intervention is regarded as an effective strategy to improve clinical symptoms, delay disease progression and maintain current quality of life. The humanized monoclonal antibody lencanemab (Lecanemab) was approved by the U.S. FDA in July 2023 for the treatment of mild cognitive impairment or mild dementia caused by AD, and was officially approved in January 2024 in China. Lencanemab highly targets soluble and insoluble neurotoxic β-amyloid (Aβ) proteins, reducing pathogenic Aβ plaque deposition and preventing its formation in the brains of AD patients, thus reducing neurotoxicity and improving patients' cognitive functions. In addition, lencanumab may also play a neuroprotective role by modulating synaptic plasticity and regulating neural network activity in brain neurons. However, there is a lack of clinical studies to prove this mechanism. In this study, we will enroll consecutive patients with early AD treated with lencanemab infusion as well as those receiving conventional anti-dementia therapy, and comprehensively assess the effects and intrinsic molecular mechanisms of lencanemab on synaptic function and neural networks using magnetic resonance imaging, molecular imaging positron emission tomography (PET), neuropsychological assessment, and analysis of blood cerebrospinal fluid samples.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
Age between 50 and 90 years.
Male or female patients.
Patients with MCI and mild AD.
MMSE score ≥20, CDR overall score of 0.5 or 1.
Disqualifiers
Patients with cognitive impairment due to reasons other than AD.
A history of transient ischemic attack (TIA), stroke, cerebral hemorrhage, or seizure within the 12 months prior to screening.
A score of >17 on the Hamilton Depression Scale at screening, or any suicidal behavior within 6 months prior to screening, at screening, or at the baseline visit, as well as any psychiatric diagnosis or symptoms that interfere with the study procedure (such as hallucinations, anxiety disorder, or paranoia).
Patients with a bleeding disorder or receiving anticoagulant therapy, as well as any with malignant tumors, severe gastrointestinal, kidney, liver, respiratory, immune, endocrine, and cardiovascular system diseases that affect this study.
Trial population
We will recruit 120 early Alzheimer's disease (AD) patients from 13 hospitals, including Xuanwu Hospital of Capital Medical University. Among them, 60 cases will be in the Lecanemab treatment group, and 60 cases in the conventional treatment group.
Trial design
Design model
Cohort
Time perspective
Prospective
Treatments tested in this trial
Lecanemab treatment group
DrugLecanemab treatment group: Lecanemab Injection Concentrate Solution (active ingredient at 100 mg/mL) is provided as a sterile aqueous solution containing 100 mg/mL of Lecanemab, 50 mmol/L citric acid, 350 mmol/L arginine/arginine hydrochloride, and 0.05% (w/v) polysorbate 80, with a pH of 5.0, and each vial is capable of being drawn into a volume of 5 mL. Lecanemab is to be administered via intravenous infusion over 60 minutes in saline solution. Lecanemab must be administered using an infusion system that includes a terminal 0.22 μM inline filter. The dosage of Lecanemab is 10 mg/kg. All subjects in the Lecanemab treatment group receive Lecanemab infusion therapy at a frequency of once every two weeks for a continuous period of 12 months.
Conventional anti-dementia treatment group
DrugConventional anti-dementia treatment: Early-stage Alzheimer's disease (AD) patients routinely take cholinesterase inhibitors such as donepezil for treatment.
Treatment groups
120 Participants
are divided into 2 treatment groupsGroup A: Lecanemab treatment group1 intervention
Group B: Conventional anti-dementia treatment1 intervention
Trial outcomes
Primary outcomes
1
Resting-state fMRI brain network metrics (Independent Component Analysis)
The Lecanemab treatment group and the conventional treatment group's longitudinal changes in Independent Component Analysis (ICA) indicators after 12 months of treatment compared to baseline. ICA is a statistical technique used for extracting mutually independent signals from multivariate data, capable of measuring levels of functional connectivity within and between networks.
Time frame
2 yearsSecondary outcomes
1
Other resting-state fMRI brain network indicators: functional connectivity (FC)
Functional Connectivity (FC) is an important concept in neuroscience, primarily used to describe and analyze the interactions between different brain regions. FC is defined by measuring the similarity between brain signals from two regions.
Time frame
2 years2
Other resting-state fMRI brain network indicators: Granger Causality Analysis (GCA)
Granger Causality Analysis: Granger causality analysis is a statistical method used to analyze the causal relationships between variables.
Time frame
2 years3
Other resting-state fMRI brain network indicators: Spectral Dynamic Causal Model (spDCM)
Spectral Dynamic Causal Model (spDCM): A method for investigating the directed interactions between brain regions, also known as effective connectivity.
Time frame
2 years4
Rate of change in global cognition as measured by Clinical Dementia Rating (CDR)
Assess statistically significant difference in score between Lecanemab treatment group and conventional anti-dementia treatment using the neuropsychological scales CDR. CDR, a multidimensional scale for dementia severity, which scored 0-3, with higher scores indicating worse functioning.
Time frame
2 yearsOther outcomes
1
Blood neuron-derived exosome transcriptomics-related indicators
Assess statistically significant difference in score between Lecanemab treatment group and Conventional anti-dementia treatment using Blood neuron-derived exosome transcriptomics-related indicators.
Time frame
2 yearsSponsors and contacts
Click on the lead sponsor to view all of their trials.
Cuibai Wei，Clinical Professor
Lead sponsor
Xuanwu Hospital, Beijing
Sponsor institution
Eisai (China) Pharmaceutical Co.
Collaborator
Jinan Hospital, Xuanwu Hospital, Capital Medical University
Collaborator
RenJi Hospital
Collaborator
First Hospital of China Medical University
Collaborator
Nanjing Brain Hospital
Collaborator
Guangdong Provincial People's Hospital
Collaborator
Zhejiang University
Collaborator
The First Affiliated Hospital of Anhui Medical University
Collaborator
The First Affiliated Hospital of University of Science and Technology of China
Collaborator
The First Hospital of Chongqing Medical University
Collaborator
Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
Collaborator
West China Hospital
Collaborator
The First Hospital of Jilin University
Collaborator
Source ClinicalTrials.gov