Clinical trial NCT06889818: Korean Joint Registry for Alzheimer's Treatment and Diagnostics (JOY-ALZ)
Official title: Korean Joint Registry for Alzheimer's Treatment and Diagnostics (JOY-ALZ)
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Mild Cognitive Impairment
Dementia
Subjective Cognitive Decline (SCD)
Alzheimer Disease
Keywords: Real World Data
Lecanemab
Lead sponsor: Ewha Womans University Mokdong Hospital
Sponsor class: OTHER
Collaborators: name: Korean Dementia Association
name: Inha University Hospital
name: Gachon University Gil Medical Center
name: Saint Vincent's Hospital, Korea
name: Gangnam Severance Hospital
name: Konkuk University Hospital
name: Kyunghee University Medical Center
name: Korea University Medicine
name: Busan University Medical Center
name: CHA University
name: Samsung Medical Center
name: Seoul National University Hospital
name: Seoul National University Bundang Hospital
name: Asan Medical Center
name: Soonchunhyang University Hospital
name: Ajou University Hospital, Suwon, South Korea
name: Yonsei University Yongin Severance Hospital
name: Wonkwang University Hospital
name: Ewha Womans University Seoul Hospital
name: InjeUniversityBusanPaikHospital
name: Chonnam National University Hospital
name: Jeju National University Hospital
name: Chungnam National University Hospital
name: Gyungbook national university hospital
name: Hanllym University Medical Center
name: Heavenly Clinical Research
name: KangWon National University Hospital
name: Seoul St. Mary's Hospital, The Catholic University
First posted: 2025-03-21
Enrollment: 4000
Sex: ALL
Minimum age (years): 19
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: CASE_ONLY
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Approximately 40 medical institutions nationwide are expected to participate in the study over a period of 10 years, with about 4,000 participants in total. Our institution anticipates the participation of approximately 100 subjects. Participants in this study are adults with Alzheimer's disease dementia, mild cognitive impairment, or normal cognitive function (including subjective cognitive decline) who are undergoing medical evaluation for newly approved Alzheimer's disease medications after 2021, have made the decision to initiate treatment with these medications, or have already begun treatment with these newly approved Alzheimer's disease medications.

Brief summary: The purpose of this research is to investigate the long-term effectiveness and safety of new Alzheimer's disease treatments, particularly monoclonal antibody therapies like lecanemab and donanemab, as well as to enhance diagnostic methods for Alzheimer's disease by collecting real-world data from Korean Alzheimer's patients. The goal is to contribute to the precision of Alzheimer's treatment and to evaluate the impact of these new therapies and diagnostic techniques in clinical practice.

Detailed description: In 2024, it is estimated that there will be over 1 million individuals aged 65 and older with dementia in South Korea, with national dementia care costs exceeding approximately 17 trillion KRW (0.9% of GDP). South Korea is experiencing rapid population aging, leading to a projected significant increase in both the number of patients and the associated socio-economic costs. Alzheimer's disease (AD) is the most common cause of dementia and cognitive impairment in the elderly, characterized by the abnormal accumulation of amyloid beta (Aβ) and tau proteins in the brain. Research has shown that beta-amyloid protein begins to accumulate in the brain over 20 years before the onset of memory impairment symptoms. Consequently, Alzheimer's disease progresses through a prolonged asymptomatic stage of normal cognitive function (cognitively unimpaired, CU) to subjective cognitive decline, mild cognitive impairment, and dementia.

In May 2024, the Korean Ministry of Food and Drug Safety approved lecanemab for the treatment of Alzheimer's disease. Recent advancements have been made in the development of new treatments and diagnostic methods for Alzheimer's disease, with some already approved for use in South Korea or anticipated to receive approval soon. These developments are expected to significantly impact the management of dementia and cognitive impairment patients in the near future. Among the new treatments, monoclonal antibody injections targeting the core pathological mechanism of Alzheimer's disease, which is the removal of beta-amyloid protein (e.g., lecanemab, donanemab), currently lack long-term efficacy data, providing only 1-2 years of investigatory data in clinical trials. Such medications may have side effects, including amyloid-related imaging abnormalities (ARIA) such as brain edema or microbleeding and infusion-related adverse reactions. For the advancement of precise treatments for Alzheimer's disease, it is essential to monitor long-term effects and side effects of these drugs in clinical practice to collect and analyze more extensive clinical data to establish additional clinical evidence.

Moreover, the phase 3 clinical trial data for lecanemab suggests that the drug's effectiveness and side effects may vary by ethnicity. Recently, a diagnostic technique that measures Elecsys beta-amyloid 42 (Aβ42) and Elecsys Phospho-Tau181 (ptau181) in cerebrospinal fluid (CSF) has received approval from the Korean Ministry of Food and Drug Safety for the diagnosis of Alzheimer's disease. Additionally, there is a strong potential for new diagnostic methods that measure proteins such as ptau217, ptau181, and Aβ42 in blood to be commercialized in clinical practice. Future advancements through real-world data collection on these new diagnostic methods will be necessary.

The Alzheimer's Association (AA) and researchers in the United States have initiated a registry study named the Alzheimer's Network for Treatment and Diagnostics (ALZ-NET) to collect real-world data on new treatments and diagnostic methods for Alzheimer's disease. Longitudinal studies to investigate the long-term effectiveness and safety of new treatments and diagnostic methods in Alzheimer's patients are also being established in countries such as Japan, Australia, the Netherlands, and Europe. In response to these changes in Alzheimer's disease management, the researchers aim to contribute to the precision of Alzheimer's treatment and the enhancement of new diagnostic methods by collecting real-world data from Korean Alzheimer's patients regarding the long-term effectiveness and safety of new therapies.

Eligibility criteria: Inclusion Criteria:

1. Participants must be 19 years of age or older at the time of informed consent.
2. Patients who are undergoing medical evaluation for newly approved Alzheimer's disease medications after 2021, patients who have decided to initiate treatment with these medications in consultation with their physician after 2021, or patients who have already started treatment with newly approved Alzheimer's disease medications after 2021.
3. Patients who have undergone an amyloid PET scan to confirm Alzheimer's disease pathology, or cerebrospinal fluid testing for Aβ42 and ptau181.
4. Clinical diagnosis of Alzheimer's disease, defined as follows:

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1. \[Alzheimer's Disease Dementia (ADD)\] - Must meet the criteria for probable Alzheimer's dementia as defined by the National Institute on Aging and the Alzheimer's Association working groups (NIA-AA).

   * Must exhibit cognitive decline that impairs independent daily living.
2. \[Mild Cognitive Impairment (MCI)\]

   - Must meet NIA-AA diagnostic criteria for MCI.

   - The subject or informant must report cognitive decline.

   - Performance on delayed recall of verbal memory must be more than -1.0 SD below the age- and education-adjusted normative mean, or scores on any one or more tests of executive function, language, visuospatial abilities, or attention must be more than -1.5 SD below the age- and education-adjusted normative mean.

   - Clinical Dementia Rating scale (CDR) of 0.5.

   - Maintenance of independent daily living ability.

   - Not categorized as dementia.
3. \[Cognitively Unimpaired (CU)\]

   - Delayed recall of verbal memory must be at or above -1.0 SD versus the age- and education-adjusted normative mean, and all executive function, language, visuospatial abilities, and attention tests must be at or above -1.5 SD versus the age- and education-adjusted normative mean.

   - Maintenance of independent daily living ability.
   * If the subject reports cognitive decline, they will be classified as having Subjective Cognitive Decline (SCD).

     5. Patients must be ambulatory (use of mobility aids is acceptable). 6. The subject must provide written informed consent to participate in the study. In the case of dementia patients, additional written consent from a guardian is required.

Exclusion Criteria:

1. Presence of significant psychiatric disorders associated with intellectual disability, schizophrenia, major depression, bipolar disorder, delirium, etc.
2. History of substance abuse or alcohol dependence that required treatment within the past five years.
3. A current diagnosis of cancer that has not achieved remission within the past five years. However, localized prostate cancer, cervical carcinoma in situ, non-melanoma skin basal cell carcinoma, or squamous cell carcinoma are excluded.
4. Evidence of severe or unstable physical conditions (e.g., dialysis, severe liver disease).
5. Visual or auditory impairments that prevent the satisfactory assessment of cognitive function.
6. Inability to perform MRI due to the presence of metallic substances in the body.
7. Currently participating in another drug clinical trial.
8. Currently pregnant or breastfeeding.

Primary outcomes:
measure: Change from baseline in the Korean Mini-Mental State Examination-2 (K-MMSE-2) total score
timeFrame: Up to 10 years
measure: Change from baseline in the Korean version of Montreal Cognitive Assessment (K-MOCA) total score
timeFrame: Up to 10 years
measure: Change from baseline in the Clinical Dementia Rating scale (CDR) total score
timeFrame: Up to 10 years
measure: Change from baseline in the Functional Assessment Questionnaire (FAQ) total score
timeFrame: Up to 10 years
measure: Change from baseline in the Korean version of the Alzheimer disease 8 (K-AD8) total score
timeFrame: Up to 10 years
Secondary outcomes:
measure: Brain Magnetic Resonance Imaging (MRI)
timeFrame: Up to 10 years
measure: Alzheimer's disease (AD) biomarkers
timeFrame: Up to 10 years
Other outcomes:
Locations:
city: Incheon
country: Korea, Republic of
facility: Gachon University Gil medical Center
city: Incheon
country: Korea, Republic of
facility: Inha University Hospital
city: Seoul
country: Korea, Republic of
facility: Ewha Womans University Mokdong Hospital
Study officials:
affiliation: Ewha Womans University Mokdong Hospital
name: Geon-ha Kim
role: PRINCIPAL_INVESTIGATOR
affiliation: Inha University Hospital
name: Seong-hye Choi
role: PRINCIPAL_INVESTIGATOR
affiliation: Gachon University Gil Medical Center
name: Kee-hyung Park
role: PRINCIPAL_INVESTIGATOR
References: