The Clinical Study of Synaptic Plasticity-based Lencanumab for the Treatment of Early Alzheimer's Disease
For patients and families
In plain language
An automatic summary of structured registry data. It is an orientation aid, not a substitute for the official protocol or a physician assessment.
- What is being studied
- The protocol lists: Lecanemab treatment group, Conventional anti-dementia treatment group.
- Who it may be relevant to
- Registry conditions: Alzheimer's Disease, Lecanemab, Functional Magnetic Resonance Imaging. Basic parameters: 50 years — 90 years · All.
- What needs checking
- Age, condition and sex are only basic indicators. Prior treatment, laboratory values and other mandatory requirements appear in the eligibility criteria below.
- Where it takes place
- China
- Next step
- Save the trial, show it to the treating physician, and confirm current recruitment with the study center. Costs, documents and travel →
Unsure about the terms? Read our patient guide →
Overview
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.
Detailed description
Alzheimer's disease (AD) is a neurodegenerative disorder characterized by cognitive decline, impairment of daily living activities, and various behavioral and psychiatric symptoms. The most widely accepted hypothesis regarding the pathogenesis of AD is the amyloid cascade hypothesis. This hypothesis posits that the abnormal deposition of neurotoxic beta-amyloid (Aβ) is a key factor in the onset of AD. In the past two decades, anti-Aβ monoclonal antibodies aimed at reducing cerebral Aβ plaques have increasingly attracted attention in the field of AD drug development.
The humanized monoclonal antibody CAb (Lecanemab) highly targets soluble and insoluble A β\[1,2\] to reduce pathogenic A β plaques and prevent their formation in the brain of AD patients. Large global phase III clinical trials, including China, show that Lecanemab can slow the rate of cognitive decline in mild cognitive impairment (MCI) and mild AD within 18 months of treatment compared with placebo. However, the intrinsic mechanism by which Lecanemab delays disease progression by clearing pathogenic A β is not well understood. Previous studies have suggested that Lecanemab may have a role in improving synaptic plasticity. An animal experiment showed that the A β antibody can reverse the long-term enhanced (LTP) synaptic function defects caused by soluble A β oligomers and improve synaptic plasticity \[4\]. Synaptic plasticity is closely related to cognitive function. It refers to the ability to establish new connections between neurons or existing connections in the brain, which is manifested by changes in ultrastructure and functional changes of synapses, such as \[5\] of neurotransmitter level, neuroexcitability, electrical activity or changes in the number of postsynaptic receptors. It was shown that soluble A β oligomers are able to strongly inhibit synaptic plasticity in the normal rodent hippocampus, damage synaptic architecture, and ultimately lead to impaired cognitive \[6\]. Based on this, the scientific hypothesis is proposed that "Lecanemab may effectively reduce A β toxicity and protect synaptic function defects in AD brain". However, further clinical studies on the mechanism of Lecanemab on synaptic plasticity.
The purpose of this study is to prospectively evaluate the impact of continuous use of luncanemab infusion therapy on brain neural networks and synaptic plasticity in early Alzheimer's disease (AD) patients, and to explore the underlying molecular pathological mechanisms. According to the inclusion and exclusion criteria, eligible subjects are included in the screening visit period. During the screening visit, informed consent is signed, and demographic assessments are completed, along with the collection of past medical history, medication history, physical examination, and laboratory tests. Baseline neuropsychological scales, resting-state fMRI, three-dimensional structural MRI, Amyloid-PET, and blood and cerebrospinal fluid sample data are also collected. Patients are divided into a luncanemab treatment group and a conventional treatment group based on whether they receive luncanemab, and are followed up for data collection over a period of 12 months. This includes four neuropsychological assessments at 3 months, 6 months, 9 months, and 12 months of follow-up; collection of neuropsychological, resting-state fMRI, three-dimensional structural MRI, Amyloid-PET, and blood samples at baseline and at the 12-month follow-up, in accordance with patient wishes for cerebrospinal fluid sample collection; and two resting-state fMRI, three-dimensional structural MRI assessments, and blood sample collection at 6 months and 12 months of follow-up.
Interventions
- Drug Lecanemab treatment group
Lecanemab 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 - Drug Conventional anti-dementia treatment group
Conventional anti-dementia treatment: Early-stage Alzheimer's disease (AD) patients routinely take cholinesterase inhibitors such as donepezil for treatment.
Primary outcome measures
- Resting-state fMRI brain network metrics (Independent Component Analysis) [Time frame: 2 years]
Secondary outcome measures (12)
- Other resting-state fMRI brain network indicators: functional connectivity (FC) [Time frame: 2 years]
- Other resting-state fMRI brain network indicators: Granger Causality Analysis (GCA) [Time frame: 2 years]
- Other resting-state fMRI brain network indicators: Spectral Dynamic Causal Model (spDCM) [Time frame: 2 years]
- Rate of change in global cognition as measured by Clinical Dementia Rating (CDR) [Time frame: 2 years]
- Rate of change in the severity of cognitive impairment as assessed by Alzheimer's Disease Assessment Scale-Cognitive section (ADAS-cog) [Time frame: 2 years]
- Rate of change in global cognition as measured by Mini-Mental State Examination (MMSE) [Time frame: 2 years]
- Rate of change in global cognition as measured by Montreal Cognitive Assessment (MoCA) [Time frame: 2 years]
- Alzheimer's Disease Composite Score (ADCOMS) [Time frame: 2 years]
- The Integrated Alzheimer's Disease Rating Scale (iADRS) [Time frame: 2 years]
- Five Levels Five-Dimensional Health Scale (EQ-5D-5L) [Time frame: 2 years]
- Alzheimer's Disease Quality of Life Scale (QOL-AD) [Time frame: 2 years]
- Rate of change in activities of daily living as assessed by Alzheimer's Disease Cooperative Study-Activity of Daily Living (ADCS-ADL) [Time frame: 2 years]
Eligibility criteria
Inclusion criteria
- 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.
- Amyloid-positive confirmed by Amyloid-PET or CSF.
- Have a reliable caregiver to accompany the patient during study visits and supervise the use of study medication during the trial.
- Agree to participate in the study and sign the informed consent form.
Exclusion criteria
- 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.
- A hypersensitivity reaction to ranucimab or any other ingredient in the injection solution, or to any monoclonal antibody treatment.
- Contraindications to MRI scanning, including those with a pacemaker/defibrillator or ferromagnetic metal implants (except for skull and cardiac devices approved as safe for MRI scanning).
- A known or suspected history of drug or alcohol abuse or dependence within the 2 years prior to screening.
- Participation in a clinical study involving any therapeutic monoclonal antibody or novel compounds for the treatment of AD within the 6 months prior to screening, unless it can be proven that the subject was in the placebo treatment group.
- Planning to undergo surgery requiring general anesthesia during the study period.
- A positive pregnancy test result, lactation, or pregnancy in females at screening or baseline.
Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.
Healthy volunteers: No
Study design
- Observational model
- Cohort
Study locations
China · 1 center
- Capital Medical University Xuanwu Hospital — Beijing
Identifiers
NCT: NCT06871839 · KS2024354