MRI + PET Scans for Cognitive Impairment

(BEACoN Trial)

Overseen By Evelyn Chang, BA

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: University of California, Irvine

Disqualifiers: Parkinson's, Schizophrenia, Bipolar, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 3

300 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to uncover how thinking and memory change with age, focusing on early signs of cognitive decline. Researchers use MRI and PET scans, alongside cognitive tests, to spot subtle brain changes. Participants will also explore the link between tau protein buildup in the brain and cognitive decline using an investigational drug, MK-6240. The study seeks individuals aged 60 and older who have normal cognition but notice memory changes or other cognitive concerns. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to a potentially groundbreaking treatment.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. However, common conditions like Type II diabetes, high cholesterol, and high blood pressure are not exclusionary, suggesting you may continue those treatments.

What prior data suggests that MRI and PET scans are safe for detecting cognitive impairment?

Research shows that the treatments in this study are generally safe and well-tolerated. The Amyloid PET scan involves a small amount of radiation, which studies have found to be within safe limits, minimizing potential risk. This scan is used for patients with memory and thinking problems and has been shown to be safe in medical settings.

The investigational drug MK-6240, used in the tau PET scan, has promising safety data. Research with older adults has shown that the drug's dosage and pharmacokinetics are well understood, which helps ensure its safe use.

MRIs are also part of the study and are commonly used in medical imaging. Although some studies mention temporary effects on thinking, MRIs are widely considered safe and are a standard tool for assessing brain changes.

Overall, the treatments in this study, including the PET scans and MRI, have been researched for safety in humans and are used in clinical settings, supporting their tolerability. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about this trial because it combines advanced imaging techniques—Amyloid and Tau PET scans—with MRI and neurocognitive testing to better understand cognitive impairment. Unlike traditional methods that might rely solely on neurocognitive assessments or basic imaging, this approach offers a comprehensive view of the brain's structural and biochemical changes. This could lead to earlier and more accurate detection of cognitive decline, potentially improving treatment strategies and outcomes for those at risk. By identifying specific biomarkers associated with impairment, this trial aims to pave the way for more personalized and effective interventions.

What evidence suggests that this trial's treatments could be effective for cognitive impairment?

This trial will use several methods to detect and understand cognitive decline. Participants in the various treatment arms will undergo Amyloid PET scans. Research has shown that these scans can change how doctors treat patients with mild memory or thinking problems by providing a clearer view of the brain. The investigational tracer MK-6240, used in these scans, has effectively tracked the buildup of tau protein, which is linked to Alzheimer's disease and related to memory and thinking issues. MRI scans, also part of the trial, aid in early diagnosis by capturing brain changes that might indicate the onset of conditions like Alzheimer's. Together, these methods help identify brain changes early, leading to better treatment planning for cognitive decline. ^{1 2 3 6 7}

Who Is on the Research Team?

Michael A Yassa, PhD

Principal Investigator

University of California, Irvine

Liv C McMillan, BS, CCRP

Principal Investigator

University of California, Irvine

Are You a Good Fit for This Trial?

This trial is for people aged 60 or older who speak English or Spanish, have good vision and hearing for tests, are in overall good health without diseases that could affect the study. They must not have significant neurological conditions like Parkinson's disease, major psychiatric disorders, uncontrolled medical issues like diabetes or hypertension, metal implants incompatible with MRI scans, nor be pregnant.

Inclusion Criteria

Willing and able to participate for the duration of the study and in all study procedures including MRI and PET

You do not have memory or thinking problems, and you score 27 or higher on a memory and thinking test.

I am in good health with no conditions that could affect the study.

Exclusion Criteria

You have been diagnosed with dementia or mild cognitive impairment by a specialist.

You cannot have an MRI if you have certain medical implants or metal in your body. If you are pregnant or trying to get pregnant, you cannot participate.

You have had problems with alcohol or drugs in the past 2 years.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Baseline Assessment

Participants undergo baseline assessments including Amyloid PET scan, Tau PET scan using MK-6240, MRI scans, and neurocognitive testing

1-2 weeks

1 visit (in-person)

Longitudinal Monitoring

Participants are monitored for cognitive outcomes through longitudinal assessments including MRI and tau PET imaging at baseline and Year 1

1 year

2 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, with outcome measures assessed in Years 4 and 5

2 years

What Are the Treatments Tested in This Trial?

Interventions

• Amyloid PET scan
• MK-6240
• MRI
• Neurocognitive testing

Trial Overview

Researchers are studying how brain imaging (MRI and PET scans) and cognitive tests can detect early changes linked to memory loss as we age. The study includes a special PET scan using MK-6240 to see if tau protein tangles in the brain relate to cognitive decline—a sign of Alzheimer's disease.

How Is the Trial Designed?

Group I: Age 81+ ApoE e4- Experimental Treatment 4 Interventions

Participants in this cohort are between the ages of 81-85 and are not ApoE e4 carriers. All participants in this cohort will complete the Amyloid PET scan, Tau PET scan using MK-6240, MRI scans, and neurocognitive testing.

Group II: Age 81+ ApoE e4+ Experimental Treatment 4 Interventions

Participants in this cohort are between the ages of 81-85 and are ApoE e4 carriers. All participants in this cohort will complete the Amyloid PET scan, Tau PET scan using MK-6240, MRI scans, and neurocognitive testing.

Group III: Age 76-80 ApoE e4- Experimental Treatment 4 Interventions

Participants in this cohort are between the ages of 76-80 and are not ApoE e4 carriers. All participants in this cohort will complete the Amyloid PET scan, Tau PET scan using MK-6240, MRI scans, and neurocognitive testing.

Group IV: Age 76-80 ApoE e4+ Experimental Treatment 4 Interventions

Participants in this cohort are between the ages of 76-80 and are ApoE e4 carriers. All participants in this cohort will complete the Amyloid PET scan, Tau PET scan using MK-6240, MRI scans, and neurocognitive testing.

Group V: Age 71-75 ApoE e4- Experimental Treatment 4 Interventions

Participants in this cohort are between the ages of 71-75 and are not ApoE e4 carriers. All participants in this cohort will complete the Amyloid PET scan, Tau PET scan using MK-6240, MRI scans, and neurocognitive testing.

Group VI: Age 71-75 ApoE e4+ Experimental Treatment 4 Interventions

Participants in this cohort are between the ages of 71-75 and are ApoE e4 carriers. All participants in this cohort will complete the Amyloid PET scan, Tau PET scan using MK-6240, MRI scans, and neurocognitive testing.

Group VII: Age 66-70 ApoE e4- Experimental Treatment 4 Interventions

Participants in this cohort are between the ages of 66-70 and are not ApoE e4 carriers. All participants in this cohort will complete the Amyloid PET scan, Tau PET scan using MK-6240, MRI scans, and neurocognitive testing.

Group VIII: Age 66-70 ApoE e4+ Experimental Treatment 4 Interventions

Participants in this cohort are between the ages of 66-70 and are ApoE e4 carriers. All participants in this cohort will complete the Amyloid PET scan, Tau PET scan using MK-6240, MRI scans, and neurocognitive testing.

Group IX: Age 60-65 ApoE e4+ Experimental Treatment 4 Interventions

Participants in this cohort are between the ages of 60-65 and are ApoE e4 carriers. All participants in this cohort will complete the Amyloid PET scan, Tau PET scan using MK-6240, MRI scans, and neurocognitive testing.

Who Is Running the Clinical Trial?

University of California, Irvine

Lead Sponsor

Trials

580

Recruited

4,943,000+

National Institute on Aging (NIA)

Collaborator

Trials

1,841

Recruited

28,150,000+

Published Research Related to This Trial

Amyloid PET imaging is effective in detecting amyloid plaques associated with Alzheimer's disease, with studies showing it can change diagnosis in about 30% of cases and increase diagnostic confidence in about 60% of cases.

The use of amyloid imaging can lead to changes in patient management and medication in approximately 60% and 40% of cases, respectively, indicating its potential clinical utility, although further research is needed to confirm these findings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical Use and Utility of Amyloid Imaging. Barthel, H., Sabri, O.[2022]

Amyloid PET imaging has been approved for clinical use and is effective in diagnosing and managing Alzheimer's disease (AD) and mild cognitive impairment (MCI), providing crucial information for uncertain cases.

The ongoing IDEAS study is assessing the impact of amyloid imaging on diagnosis and treatment outcomes in cognitively impaired patients, highlighting its role in evaluating potential therapies for AD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical Amyloid Imaging. Mallik, A., Drzezga, A., Minoshima, S.[2017]

In a phase 1b trial involving 278 patients with early stages of Alzheimer's disease, amyloid PET imaging successfully identified 61% of patients as amyloid-positive, making it a promising tool for selecting participants for clinical trials.

The study found that ApoE ε4 carriers were more likely to be amyloid-positive (80%) compared to noncarriers (43%), highlighting the potential of PET imaging to enrich trial populations based on genetic risk factors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Amyloid PET Screening for Enrichment of Early-Stage Alzheimer Disease Clinical Trials: Experience in a Phase 1b Clinical Trial. Sevigny, J., Suhy, J., Chiao, P., et al.[2022]

The preclinical studies showed that [18F]MK-6240 is safe for use, with no adverse effects observed in rats at doses up to 1000 times the anticipated clinical dose, indicating a strong safety profile for human use.

In human studies, [18F]MK-6240 demonstrated effective biodistribution for brain imaging, with a low effective dose of 5.4 mSv per scan, allowing for multiple imaging sessions per year without significant risk.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preclinical Safety Evaluation and Human Dosimetry of [18F]MK-6240, a Novel PET Tracer for Imaging Neurofibrillary Tangles. Koole, M., Lohith, TG., Valentine, JL., et al.[2021]

Amyloid PET imaging is an important diagnostic tool that can detect amyloid-β deposits in the brains of living individuals, helping to confirm Alzheimer disease diagnoses in specific patient populations.

The Amyloid Imaging Task Force has clarified guidelines for the appropriate use of amyloid PET scans, including criteria for dementia experts, specific cases of mild cognitive impairment, and the need for educational programs to enhance understanding of these criteria in clinical practice.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Update on appropriate use criteria for amyloid PET imaging: dementia experts, mild cognitive impairment, and education. Amyloid Imaging Task Force of the Alzheimer’s Association and Society for Nuclear Medicine and Molecular Imaging. Johnson, KA., Minoshima, S., Bohnen, NI., et al.[2021]

Amyloid PET imaging can lead to significant changes in the diagnosis of Alzheimer's disease, with a pooled estimate showing a 31% change rate across 16 studies involving various patient populations.

The imaging technique also increases diagnostic confidence and influences patient management decisions, particularly in cases where there is high diagnostic uncertainty, affecting treatment plans for Alzheimer's medications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Review of Diagnostic Impact of Amyloid Positron Emission Tomography Imaging in Clinical Practice. Kim, Y., Rosenberg, P., Oh, E.[2019]

Using deep learning methods, researchers were able to synthesize high-quality amyloid PET images from only 1% of the radiotracer typically required, without compromising diagnostic quality, based on a study of 39 patients.

The PET-plus-MR model significantly improved image quality and maintained high accuracy in determining amyloid status, achieving 89% accuracy in readings, which is comparable to full-dose PET images.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ultra-Low-Dose 18F-Florbetaben Amyloid PET Imaging Using Deep Learning with Multi-Contrast MRI Inputs. Chen, KT., Gong, E., de Carvalho Macruz, FB., et al.[2022]

(18)F-labeled PET tracers for imaging brain β-amyloid plaques are becoming essential tools for diagnosing Alzheimer's disease (AD), especially as the prevalence of AD increases with an aging population.

Nuclear medicine physicians will need to understand the relationship between amyloid presence and cognitive decline, as well as how to properly acquire, display, and interpret PET scan images to effectively diagnose AD and differentiate it from other dementias.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Brain amyloid imaging. Rowe, CC., Villemagne, VL.[2020]

A systematic review of 10 papers from 7 studies found that disclosing amyloid PET scan results generally did not lead to increased depression among individuals with cognitive impairment, but those with mild cognitive impairment and high amyloid levels experienced more distress or anxiety.

While participants remembered their scan results, it remains uncertain if this improved their understanding of their diagnosis, indicating a need for further research on the psychosocial impacts of amyloid PET scans.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Psychosocial and Behavioral Outcomes for Persons With Cognitive Impairment and Caregivers Following Amyloid-β PET Scan Disclosure: A Systematic Review. Couch, E., Ashford, MT., Zhang, W., et al.[2023]

(18)F-labeled PET tracers for imaging brain β-amyloid plaques are becoming essential tools for diagnosing Alzheimer's disease, especially as the condition's prevalence increases with an aging population.

Physicians will need to understand the relationship between amyloid presence and cognitive decline, as well as how to properly acquire and interpret PET images to differentiate Alzheimer's from other types of dementia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Brain amyloid imaging. Rowe, CC., Villemagne, VL.[2013]

Amyloid PET (aPET) imaging led to a revision of diagnoses in 31.3% of cases among cognitively impaired subjects, significantly higher than the 3.2% revision rate in control patients with delayed feedback, indicating its strong impact on diagnostic accuracy.

Following aPET, 62.1% of patients experienced increased diagnostic confidence, and 72.2% had changes in management plans, highlighting its effectiveness in improving patient care and treatment strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Systematic Review and Aggregated Analysis on the Impact of Amyloid PET Brain Imaging on the Diagnosis, Diagnostic Confidence, and Management of Patients being Evaluated for Alzheimer's Disease. Fantoni, ER., Chalkidou, A., O' Brien, JT., et al.[2023]

Citations

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Amyloid PET disclosure in subjective cognitive decline

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Amyloid PET imaging: applications beyond Alzheimer's disease

Amyloid PET imaging offers a unique possibility to explore the relationships between beta-amyloid depositions and clinical outcomes during life.