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

NCT07456462 | Not Yet Recruiting DMC

• 1 other identifier: AMYTRACK
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Alzheimer Dementia (AD); Mild Cognitive Impairment (MCI)

Keywords

Alzheimer's disease; Amyloid; Monoclonal antibody therapy; Lecanemab; Donanemab; Precision medicine; Predictive modeling; 3 Tesla Magnetic Resonance; Amyloid Tomography Emission Positron (PET); Plasma biomarkers

Outcome Measures

Primary Outcomes (2)

• Predicting time (in months) to amyloid [¹⁸F]Flutemetamol (amyloid) PET negativity on a single scan

  Predicting time (in months) to amyloid \[¹⁸F\]Flutemetamol (amyloid) PET negativity, defined as amyloid load \<11 Centiloids on a single scan

  baseline, 6 months, 12 months and 18 months

• Predicting time (in months) to amyloid [¹⁸F]Flutemetamol (amyloid) PET negativity on two consecutive scans

  Predicting time (in months) to amyloid \[¹⁸F\]Flutemetamol (amyloid) PET negativity, defined as amyloid load -\<25 Centiloids on two consecutive scans

  Baseline, 6 months, 12 months, 18 months

Secondary Outcomes (14)

• Change in regional cerebral perfusion expressed in Standardized Uptake Volume Ratio (SUVR)

  6 months, 12 months, 18 months

• Change in global cerebral perfusion expressed in Standardized Uptake Volume Ratio (SUVR)

  6 months, 12 months, 18 months

• Longitudinal change in brain volume

  6 months, 12 months, 18 months

• Longitudinal change in white matter integrity via Neurite Orientation Dispersion and Density Imaging (NODDI)

  6 months, 12 months, 18 months

• Longitudinal change in brain connectivity via functional MRI

  6 months, 12 months, 18 months

Study Arms (1)

Participants with Alzheimer's disease and Mild Cognitive Impairment (MCI)

EXPERIMENTAL

Participants with AD or MCI receiving monoclonal antibody therapy (lecanemab or donanemab) administered as clinical practice.

Other: MRI assessment and blood sample collection

Interventions

MRI assessment and blood sample collection OTHER

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, multimodal predictive models, using the Aggregation Network Diffusion (AND) model, based on baseline amyloid burden, structural and functional brain connectivity, and clinical, cognitive and plasma biomarkers will be developed to estimate the time to significant amyloid reduction in patients with MCI or mild AD treated with lecanemab or donanemab

Participants with Alzheimer's disease and Mild Cognitive Impairment (MCI)

Eligibility Criteria

• Age: 30 Years - 90 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participant is willing and able to give informed consent for participation in the study.
• \. 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.
• \. 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.
• \. For males of reproductive potential: use of condoms or other methods to ensure effective contraception with partner.

You may not qualify if:

• \. 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).
• \. 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.
• \. Inability to undergo MRI or PET imaging procedures (e.g. non-MRI safe pacemaker or devices, claustrophobia etc).
• \. Women of childbearing potential who are not using adequate contraception, as well as pregnant or breastfeeding women.

Sponsors & Collaborators

• IRCCS San Raffaele: lead

Study Sites (1)

San Raffaele Neurology Unit

Milan, Milano, 20132, Italy

Location

MeSH Terms

Conditions

Alzheimer Disease; Cognitive Dysfunction

Condition Hierarchy (Ancestors)

Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases; Neurocognitive Disorders; Mental Disorders; Cognition Disorders

Study Officials

• Massimo Filippi

  IRCCS San Raffaele

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Federica FA Agosta, MD

CONTACT

0226433051; agosta.federica@hsr.it

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Prof, MD

Model Details: Interventional study on procedure (3T brain MRI)

Study Record Dates

• First Submitted: February 24, 2026
• First Posted: March 6, 2026
• Study Start: May 1, 2026
• Primary Completion (Estimated): May 1, 2028
• Study Completion (Estimated): May 1, 2029
• Last Updated: March 6, 2026

Record last verified: 2026-03

Locations

IT (1)