Making Antibody Treatments More Effective in Early Alzheimer's Disease Using 3Tesla Magnetica Resonance

Официальное название

Precision Monitoring and Predictive Models for Optimizing Monoclonal Antibody Therapy in Early Alzheimer's Disease - A Prospective Monocenter Interventional Study on 3T MRI

Обзор

Alzheimer's disease causes progressive memory and cognitive decline, driven in part by the buildup of a protein called β-amyloid in the brain. New antibody therapies - lecanemab and donanemab - can remove amyloid and slow down the disease in its early stages. However, it is still unclear how long each patient should continue treatment or when it is safe to stop, because amyloid is cleared at different rates across individuals. Today, amyloid Positron Emission Tomography (PET) scans are used to measure whether amyloid has been removed from the brain, but these scans are expensive, not always available, and expose patients to radiation. Since repeated PET scans are not ideal, doctors need better ways to monitor treatment progress. This study will use advanced brain Magnetic Resonance Imaging (MRI) and blood tests to create personalized prediction models. These models will simulate how amyloid spreads or clears in each person's brain and help identify when treatment is still needed. With this approach, monitoring becomes safer, more efficient, and more affordable - helping ensure that each patient receives the right treatment for the right amount of time. This prospective monocenter study investigates the role of 3Tesla MRI-based predictive modeling in predicting treatment response to anti-amyloid monoclonal antibodies (lecanemab or donanemab administered as clinical practice) in 50 patients with early Alzheimer's disease (AD) at IRCCS Ospedale San Raffaele (Milan, Italy). Advanced MRI techniques, including high- resolution structural imaging for cortical thickness and volumetric atrophy, diffusion imaging for structural connectivity, and resting-state functional MRI for functional network analysis, will be acquired at baseline, 6, 12, and 18 months. These multimodal MRI measures will be integrated into computational approaches, such as the Aggregation Network Diffusion (AND) model, to simulate individual disease trajectories and predict the probability of achieving negativity at amyloid PET under treatment. While serial \[¹⁸F\]Flutemetamol PET will be performed as part of standard clinical practice to confirm amyloid removal, the focus of the study is on developing MRI- derived predictive biomarkers. The ultimate goal is to establish robust, non-invasive models capable of guiding individualized treatment monitoring and supporting evidence-based decisions on treatment discontinuation Overall, the project aims to support more precise care for people with early Alzheimer's disease, while reducing unnecessary procedures and improving quality of life.

Вмешательства

• Другое MRI assessment and blood sample collection
  Participants will undergo non-contrast-enhanced 3T MRI, including structural, diffusion, and functional sequences, to assess brain atrophy, connectivity, and other imaging markers relevant to disease progression and treatment response. Peripheral venous blood will be collected at scheduled study visits to measure plasma biomarkers associated with amyloid, tau, and neurodegeneration, providing complementary information on treatment effects through a minimally invasive method. Eventually, multim

Первичные конечные точки

• Predicting time (in months) to amyloid [¹⁸F]Flutemetamol (amyloid) PET negativity on a single scan [Срок оценки: baseline, 6 months, 12 months and 18 months]
• Predicting time (in months) to amyloid [¹⁸F]Flutemetamol (amyloid) PET negativity on two consecutive scans [Срок оценки: Baseline, 6 months, 12 months, 18 months]

Вторичные конечные точки (12)

• Change in regional cerebral perfusion expressed in Standardized Uptake Volume Ratio (SUVR) [Срок оценки: 6 months, 12 months, 18 months]
• Change in global cerebral perfusion expressed in Standardized Uptake Volume Ratio (SUVR) [Срок оценки: 6 months, 12 months, 18 months]
• Longitudinal change in brain volume [Срок оценки: 6 months, 12 months, 18 months]
• Longitudinal change in white matter integrity via Neurite Orientation Dispersion and Density Imaging (NODDI) [Срок оценки: 6 months, 12 months, 18 months]
• Longitudinal change in brain connectivity via functional MRI [Срок оценки: 6 months, 12 months, 18 months]
• Change from baseline in plasma biomarkers Aβ42/Aβ40 [Срок оценки: 6 months, 12 months, 18 months]
• Change from baseline in plasma biomarkers pTau217 [Срок оценки: 6 months, 12 months, 18 months]
• Changes from baseline in plasma biomarkers pTau181 [Срок оценки: 6 months, 12 months, 18 months]
• Changes from baseline in plasma biomarkers NfL [Срок оценки: 6 months, 12 months, 18 months]
• Changes from baseline in plasma biomarkers GFAP [Срок оценки: 6 months, 12 months, 18 months]
• Change from baseline in Mini Mental Score examination (MMSE) [Срок оценки: 6 months, 12 months, 18 months]
• Change from baseline in Alzheimer's Disease Assessment Scale's cognitive score (ADAS-Cog) [Срок оценки: 6 months, 12 months, 18 months]

Критерии участия

Критерии включения

1Participant is willing and able to give informed consent for participation in the study.

2\. Participant is eligible for anti-amyloid therapy (AAT), i.e.:

• Participants aged 30-90.
• Diagnosis of early symptomatic AD, including MCI or mild dementia \[2\].
• Global Clinical Dementia Rating (CDR) score of 0.5 or 1.0
• Confirmed amyloid pathology through CSF or PET imaging. 3. Participant is willing to start Anti-amyloid therapy as part of his/her clinical-practice- therapeutic plan.

4\. For females of reproductive potential: use of highly effective contraception for at least 1 month prior to screening and agreement to use such a method during study participation and for an additional four weeks after the end of study.

5\. For males of reproductive potential: use of condoms or other methods to ensure effective contraception with partner.

Критерии исключения

• 1\. Contraindications to AAT, including:

• Significant neurological diseases other than AD that could affect cognition or study participation (e.g., other dementias, serious brain infections, Parkinson's disease, multiple concussions, epilepsy with recurrent seizures).
• Homozygous ApoE4 genotype.
• Current use of anticoagulant therapy.
• Vascular abnormalities: Presence of more than 4 microhemorrhages (defined as ≤10 mm in greatest diameter), a single macrohemorrhage >10 mm, superficial siderosis, evidence of vasogenic edema, multiple lacunar infarcts, or stroke involving a major vascular territory.
• Amyloid-Related Imaging Abnormalities (ARIA): Evidence of ARIA, including cerebral amyloid angiopathy-related inflammation (CAA-ri) or amyloid beta-related angiitis (ABRA).
• Bleeding disorders: History of bleeding disorders not under adequate control, including a platelet count <50,000 or international normalized ratio (INR) >1.5 for participants not on anticoagulant therapy.
• Being currently under treatment with another AAT other than lecanemab/donanemab (e.g. as part of a Clinical Trial).

2\. Current serious or unstable illnesses, including:

• Cardiovascular, hepatic, renal, gastrointestinal, respiratory, endocrinologic, neurologic (other than AD), psychiatric, immunologic, or hematologic diseases.
• Conditions that, in the clinician's opinion, could interfere with study analyses or with a life expectancy of less than 24 months.
• History of cancer within the last 5 years, except for non-metastatic basal and/or squamous cell carcinoma of the skin, in situ cervical cancer, non-progressive prostate cancer, or other cancers with low risk of recurrence.

3\. Inability to undergo MRI or PET imaging procedures (e.g. non-MRI safe pacemaker or devices, claustrophobia etc).

4\. Women of childbearing potential who are not using adequate contraception, as well as pregnant or breastfeeding women.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Не применимо

Модель

Одна группа

Маскирование

Открытое

Основная цель

Другое

Центры проведения

Италия · 1 центр

• San Raffaele Neurology Unit — Milan

Идентификаторы

NCT: NCT07456462 · AMYTRACK

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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