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

Trial Summary

What is the purpose of this trial?

The purpose of this research study is to understand the factors that underlie changes in thinking and memory with increasing age. The investigators will test the usefulness of MRI, PET, and cognitive testing in detecting subtle changes in the brain that precede cognitive decline. An addendum to this study includes additional PET scans to examine the relationship between tau protein in the brain and cognitive decline. Tau is a protein that is known to form tangles in the areas of the brain important for memory, and these tau tangles are a hallmark of Alzheimer's disease. This sub-study research aims to look at the tau accumulation in the brain using an investigational drug called MK-6240, which is a radio tracer that gets injected prior to a positron emission tomography (PET) scan.

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 data supports the effectiveness of the treatment involving MRI and PET scans for cognitive impairment?

Amyloid PET imaging is effective in identifying amyloid plaques, which are linked to Alzheimer's disease, and can improve diagnosis and management in about 60% of cases. It also increases diagnostic confidence and can lead to changes in patient management and medication. ^{1 2 3 4 5}

Is the combination of MRI and PET scans safe for humans?

Research indicates that amyloid PET imaging, which is part of the MRI and PET scan combination, is generally safe for humans when used appropriately. Studies have shown that it is a noninvasive method and has been approved for clinical use, with safety data available from preclinical and human studies. ^{1 3 6 7 8}

How does the MRI + PET scan treatment for cognitive impairment differ from other treatments?

The MRI + PET scan treatment is unique because it combines imaging techniques to detect amyloid plaques in the brain, which are linked to Alzheimer's disease, allowing for early and accurate diagnosis. This approach is different from other treatments as it focuses on identifying the presence of amyloid plaques rather than treating symptoms directly. ^{3 7 9 10 11}

Research Team

Michael A Yassa, PhD

Principal Investigator

University of California, Irvine

Liv C McMillan, BS, CCRP

Principal Investigator

University of California, Irvine

Eligibility Criteria

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

I speak English or Spanish fluently.

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.

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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]

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]

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, 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]

(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]

References

1. United States pubmed.ncbi.nlm.nih.gov

Clinical Use and Utility of Amyloid Imaging. [2022]

2. United States pubmed.ncbi.nlm.nih.gov

Clinical Amyloid Imaging. [2017]

3. United States pubmed.ncbi.nlm.nih.gov

Amyloid PET Screening for Enrichment of Early-Stage Alzheimer Disease Clinical Trials: Experience in a Phase 1b Clinical Trial. [2022]

4. Netherlands 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. [2023]

5. United States 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. [2023]

6. Switzerland pubmed.ncbi.nlm.nih.gov

A Review of Diagnostic Impact of Amyloid Positron Emission Tomography Imaging in Clinical Practice. [2019]

7. United States 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. [2021]

8. United States pubmed.ncbi.nlm.nih.gov

Preclinical Safety Evaluation and Human Dosimetry of [18F]MK-6240, a Novel PET Tracer for Imaging Neurofibrillary Tangles. [2021]

9. United States pubmed.ncbi.nlm.nih.gov

Ultra-Low-Dose 18F-Florbetaben Amyloid PET Imaging Using Deep Learning with Multi-Contrast MRI Inputs. [2022]

10. United States pubmed.ncbi.nlm.nih.gov

Brain amyloid imaging. [2013]

11. United States pubmed.ncbi.nlm.nih.gov

Brain amyloid imaging. [2020]