Clinical trial NCT06868030: Efficacy and Safety of Conventional Symptomatic Drugs Combined with Lencanizumab in the Treatment of Early Alzheimer's Disease: a Multicenter, Prospective, Observational Study
Official title: Efficacy and Safety of Conventional Symptomatic Drugs Combined with Lencanizumab in the Treatment of Early Alzheimer's Disease: a Multicenter, Prospective, Observational Study
Study type: OBSERVATIONAL
Overall status: NOT_YET_RECRUITING
Conditions: Alzheimer's Disease
MCI-AD, Early Stage Alzheimer&#39;s Disease
Keywords: Alzheimer disease
MCI-AD, early stage Alzheimer&#39;s disease
lencanizumab
treatment
Lead sponsor: First Hospital of China Medical University
Sponsor class: OTHER
First posted: 2025-03-10
Enrollment: 120
Sex: ALL
Minimum age (years): 50
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: From January 2025 to June 2025, 120 patients with early AD (MCI-AD and mild AD) who met the inclusion and exclusion criteria and were confirmed to have amyloid protein deposition by biomarkers were selected from 10 centers. Among them, 60 patients were treated with lecanemab combined with symptomatic medication, and the other 60 patients were treated with conventional symptomatic medication.

Brief summary: According to the World Health Organization, China will become the "oldest" country in the world by 2050, with 35 percent of the elderly population. At present, in the Chinese population of 60 years old, there are about 15.07 million dementia patients (about 6.0%), about 9.83 million Alzheimer's disease (AD) patients (about 3.9%), and about 38.77 million mild cognitive impairment (Mild cognitive impairment, MCI) patients (about 15.5%). A sharp increase in older people with cognitive impairment will bring a heavy disease burden, and the social cost is almost the sum of cancer, heart disease and stroke.

AD is an age-related neurodegenerative disorder characterized by a progressive decline in cognitive function and daily living capacity. The amyloid hypothesis of AD suggests that the deposition of A β is an early and inevitable event in AD pathogenesis. This hypothesis suggests that therapies that slow the deposition of A β plaques in the brain or increase the clearance of A β may slow the progression of the AD clinical syndrome. Most of the disease course of patients with cognitive impairment is more than 10 years long. How to diagnose and treat them in the early stage has become a key link to delay the progression of the disease and reduce the burden. The disease progression of AD is divided into three major stages: preclinical AD (Preclinical AD, Pre-AD), AD-derived mild cognitive impairment (Mild cognitive impairment due to AD, MCI-AD) and AD dementia (which can be subdivided into mild, moderate and severe AD). Among them, MCI-AD and mild AD are collectively known as early AD, which are the earliest clinical symptoms and the best window for identification and intervention. Studies show that about 43.4% of patients with MCI-AD will progress to AD dementia within 4 years, and 80% will progress within 6 years. If the disease advances to moderate or severe AD, patients will develop severe cognitive, functional impairment and behavioral symptoms, which interfere with social function and need help from daily living activities; severe or even complete loss of independence, requiring round-the-clock care. If early diagnosis and effective interventions in the early stages of the disease, it will help delay the disease into the moderate and severe stages, prolong the quality of life of patients, and greatly reduce the social burden of care and treatment.

At present, the treatment of AD is mainly symptomatic treatment, mainly including cholinesterase inhibitors and NMDA receptor antagonists. Phase-phase clinical trials show that luncinelizumab has a positive impact on cognitive function and pathological indicators in patients with early AD, delaying the early AD disease process by up to 27% relative to placebo treatment. Lencanizumab, a disease-modifying therapy for early AD, has been approved by FDA and NMPA in China. With the wide clinical application, the clinical efficacy and safety of lencanizumab combined with classical symptomatic therapy have attracted great attention. However, there are still few studies on the clinical characteristics, diagnosis and treatment patterns, efficacy and safety of the combination, and clinical outcomes of patients with early AD in the real world.

Based on this, this study intends to conduct an 18-month multi-center prospective real-world observational cohort study exploring the clinical characteristics, diagnosis and treatment patterns, efficacy and safety of the combination, caregiver and family burden of real-world early AD patients (MCI-AD and mild AD).

Detailed description: This study aims to establish a multicenter prospective real-world observational cohort study covering Northeast China, aiming to explore the clinical efficacy and safety of early AD patients combined with conventional drug therapy (luncainizumab combined with conventional drugs), describe the biomarkers and neuroimaging characteristics of early AD (MCI-AD and mild AD) patients in Northeast China; evaluate the cognitive function, daily living ability and neuropsychiatric symptoms of follow-up early AD patients for 18 months; Vertical investigation of family economic burden, caregiver burden, and medical resource utilization in early AD patients in northeast China. It further describes the clinical characteristics, diagnosis and treatment patterns, and the changes of related health outcomes in northeast China in the real world clinical diagnosis and treatment environment.

This study is an 18-month multicenter real-world observational cohort study of 120 early AD patients (MCI-AD and mild AD) attending at 6 centers from January to June 2025, completed the first annual visit from July to December 2025, the second annual visit from January to June 2026, and the third annual visit from July to December 2026.

Eligibility criteria: Inclusion Criteria:

1. Patients aged 50 and 85 years old, male or female;
2. The subjects had primary school education (education) or above, normal hearing, vision and pronunciation, native tongue is Chinese, and daily language is Mandarin, and were able to complete the information collection stipulated in the program.
3. The AD diagnosis met the diagnostic criteria for dementia described in the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV-R), using the 2011 NIA-AA AD diagnostic criteria. The MCI diagnosis met the MCI diagnostic criteria of Peterson in 2004;
4. The presence of amyloid deposits was confirmed by biomarkers: imaging or cerebrospinal fluid biomarkers.
5. Having cognitive decline, having one of the following conditions: (a) MMSE score of 20 or above; (b) CDR-GS score of 0.5 or 1;
6. The combination group met the criteria for cainumab (according to cainumab instructions);
7. Willing and able to complete all the requirements of the study (including MRI, neuropsychological assessment, clinical genotyping, etc.);
8. Established caregivers or family members can objectively conduct CDR, quality of life scale, daily life performance scale and other clinical assessments;
9. The patient and their family members were informed and signed the informed consent form.

Exclusion Criteria:

1. There are other neurological diseases that can cause brain dysfunction (such as depression, brain tumors, Parkinson's disease, metabolic encephalopathy, encephalitis, multiple sclerosis, epilepsy, brain trauma, normal skull pressure hydrocephalus, etc.);
2. There are other systemic diseases that can cause cognitive impairment (such as liver insufficiency, renal insufficiency, thyroid dysfunction, severe anemia, folic acid or vitamin B12 deficiency, syphilis, HIV infection, alcohol and drug abuse, etc.);
3. Presence of serious or unstable diseases, including cardiovascular, hepatic, renal, gastrointestinal, respiratory, endocrine, neurological (except AD), psychiatric, immune, or hematological diseases and other diseases that the investigator believes may affect the results of the study analysis, or a life expectancy of \<24 months;
4. History of schizophrenia, schiztive disorder, major depression or bipolar disorder, and history of major depression may be enrolled in the study if no episodes occurred or mitigated or controlled in the past year; risk of suicide; a history of alcoholism and / or substance abuse or dependence in the past 2 years (according to the Diagnostic and Statistical Manual of Mental Disorders, Version 5th standard)
5. Severe stroke sequelae (mRS\> 3 or previous stroke history);
6. Clinically significant systemic immune participants due to the sustained effects of immunosuppressive drugs;
7. Failure to tolerate MRI tests or with MRI contraindications, including but not limited to: a pacemaker incompatible with MRI, eye, skin, MRI clips, artificial heart valve, ear implant, or external metal implant, or other clinical history or findings of which MRI may cause potential harm;
8. Subjects with a history of allergy to any treatment component such as cincainizumab;
9. Refusal to sign the informed consent form.

Primary outcomes:
measure: Efficacy and safety of conventional symptomatic drugs combined with lencanizumab in the treatment of early Alzheimer's disease
timeFrame: After collecting the medical information of each follow-up period, the measurement and analysis results will be measured and analyzed.
Secondary outcomes:
Other outcomes:
Locations:
Study officials:
affiliation: the first affiliated hospital of China medical university, neurology department
name: Huayan Liu
role: STUDY_CHAIR
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