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

Plain English Summary

Making Antibody Treatments More Effective in Early Alzheimer's Disease Using 3Tesla Magnetica Resonance is a Not Applicable clinical trial sponsored by IRCCS San Raffaele studying Alzheimer Dementia (AD), Mild Cognitive Impairment (MCI). This study tests if advanced MRI scans and blood tests can predict how well antibody treatments for early Alzheimer's disease are working. It is for individuals with early Alzheimer's disease or mild cognitive impairment who are eligible for or starting antibody treatments. Participants will have regular MRI scans and blood draws over 18 months. Current methods to check treatment effectiveness, like PET scans, are expensive and involve radiation; this study aims for a safer, more efficient alternative. The trial aims to enroll 50 participants.

Official 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 achievin

Who Can Participate

Here is what you need to know about eligibility for this trial. You can join if you are between 30 and 90 years old, have early Alzheimer's or mild cognitive impairment, and have confirmed amyloid buildup in your brain. You must be eligible for and willing to start antibody treatment as part of your regular medical care. You cannot join if you have other serious brain conditions, certain vascular issues, a history of bleeding disorders, or are currently on anticoagulant therapy. Individuals with pacemakers or other MRI-unsafe devices, or those unable to undergo MRI scans, cannot participate. This trial is studying Alzheimer Dementia (AD), Mild Cognitive Impairment (MCI), so participants generally need a confirmed diagnosis.

What They're Measuring

The primary outcome measures will help doctors predict when amyloid buildup in the brain has been cleared enough by the antibody treatment, indicating it might be time to reassess or stop the therapy. The specific primary outcome measures are: Predicting time (in months) to amyloid [¹⁸F]Flutemetamol (amyloid) PET negativity 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 (Baseline, 6 months, 12 months, 18 months). These endpoints are how researchers determine whether the treatment is effective and will form the basis of any future regulatory submissions.

About This Phase

This study does not have a traditional clinical phase designation. It may be an observational study that follows patients without intervening in their care, an expanded access or compassionate use program, or other non-interventional research. These studies contribute valuable data about disease progression, treatment patterns, and patient outcomes.

Why This Trial Matters

This trial matters because it seeks to improve how we monitor new antibody treatments for Alzheimer's, aiming to ensure patients receive the right treatment for the optimal duration without relying on This research targets Alzheimer Dementia (AD), Mild Cognitive Impairment (MCI), where improved treatment options are needed.

Investor Insight

This trial addresses a significant unmet need in managing Alzheimer's antibody therapies, a rapidly growing market, by developing a more accessible and cost-effective monitoring solution, potentially

Is This Trial Right for Me?

Ask your doctor if this study is right for you and how it differs from standard monitoring. Be prepared for regular visits over 18 months, involving MRI scans and blood draws. Discuss any concerns about claustrophobia or medical devices that might affect MRI participation. The trial is being conducted at 1 site. Always discuss clinical trial participation with your healthcare provider before making any decisions. This information is for educational purposes only and is not medical advice.

AI-generated analysis for educational purposes only. This is not medical advice. Discuss clinical trial participation with your doctor. Data sourced from ClinicalTrials.gov.

Study Design

• Study Type: INTERVENTIONAL
• Allocation: NA
• Model: SINGLE_GROUP
• Masking: NONE
• Enrollment: 50 participants

Interventions

• OTHER: 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

Primary Outcomes

• Predicting time (in months) to amyloid [¹⁸F]Flutemetamol (amyloid) PET negativity 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 (Baseline, 6 months, 12 months, 18 months)

Secondary Outcomes

• 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)

Full Eligibility Criteria

Inclusion Criteria:

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.

Exclusion Criteria:

* 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.

Trial Locations

• San Raffaele Neurology Unit, Milan, Milano, Italy

Frequently Asked Questions

Related Conditions

• Alzheimer's Disease
• Mild Cognitive Impairment
• Dementia
• Amyloidosis
• Neurodegenerative Diseases
• Neurology
• Clinical Trials
• Medical Imaging
• Monoclonal Antibody Therapy
• Biomarkers

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