Tau PET Imaging for Metabolic Health

(NOMEM-Tau Trial)

Recruiting at 1 trial location

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Columbia University

Disqualifiers: Dementia, Uncontrolled epilepsy, Liver cirrhosis, others

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

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

Compensation: Varies

Number of Visits: 4

600 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

Is 18F-MK6240 injection safe for humans?

The research on a similar tau PET tracer, 18F-PI-2620, showed that it was safe and well tolerated in both Alzheimer's patients and healthy individuals. ^{1 2 3 4 5}

How does the drug used in the Tau PET Imaging for Metabolic Health trial differ from other treatments?

The drug used in the trial, likely a tau PET tracer like [18F]PI-2620, is unique because it allows for the visualization of tau deposits in the brain, which are associated with Alzheimer's disease. This imaging capability helps in assessing the extent of tau pathology, providing a noninvasive way to monitor disease progression and potentially evaluate the effectiveness of treatments, unlike traditional therapies that do not offer such direct insights into brain changes. ^{1 2 3 4 6}

What is the purpose of this trial?

This is a single center brain Positron Emission Tomography (PET) study of 18F-MK-6240. Eligible participants are persons from Northern Manhattan who self-identify as Hispanic, non-Hispanic Black, or Non-Hispanic White, who are 55 to 69 years of age, of both sexes, without dementia, who have already agreed to undergo, of have undergone, brain amyloid PET and magnetic resonance imaging (MRI). Those eligible will have one brain PET scan with 18F-MK-6240, repeated after 18 months to 30 months. Vital signs will be checked prior to injection of 18F-MK-6240 and again at the completion of the PET scan. The primary objective is to relate diabetes status and glycemia to in-vivo brain tau accumulation, across and within ethnic and racial groups.

Research Team

Jose A. Luchsinger, MD

Principal Investigator

Columbia University

Eligibility Criteria

This trial is for people aged 55-69 living in Northern Manhattan who self-identify as Hispanic, non-Hispanic Black, or Non-Hispanic White. Participants must be fluent in English/Spanish, without dementia, and have agreed to brain scans (MRI & amyloid PET). Exclusions include serious chronic conditions like liver cirrhosis or renal failure, MRI contraindications, severe injuries, claustrophobia, inability to draw blood or have a catheter inserted.

Inclusion Criteria

I am between 55 and 69 years old.

Without dementia

Living in Northern Manhattan

Exclusion Criteria

Breastfeeding women will be excluded, although this situation is expected to be rare

I have been diagnosed with dementia.

Contraindication to MRI scanning

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Imaging Procedures

Participants undergo brain MRI and PET scans with 18F-MK-6240

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after imaging procedures

18 to 30 months

2 visits (in-person)

Treatment Details

Interventions

• 18F-MK6240 injection

Trial Overview The study tests the relationship between diabetes status and brain tau accumulation using an injection of a tracer called 18F-MK6240 with PET scans. Participants will undergo two PET scans about 18-30 months apart to measure changes in tau levels across different ethnicities and races.

Participant Groups

Group I: 18F-MK6240 injection Experimental Treatment 1 Intervention

intravenous injection of 18F-MK-6240, up to 5 mCi (185 MBq), IV, total of one injection per PET scan (2 injections in total with an interval of 18 to 30 months)

Who Is Running the Clinical Trial?

Columbia University

Lead Sponsor

Trials

1,529

Recruited

2,832,000+

Hebrew Home at Riverdale

Collaborator

Trials

6

Recruited

2,500+

National Institute on Aging (NIA)

Collaborator

Trials

1,841

Recruited

28,150,000+

Findings from Research

The PET imaging agent [18F]MK6240 effectively detects tau aggregates in the brain, showing a wide dynamic range of uptake in subjects with mild cognitive impairment (MCI) and Alzheimer's Disease (AD), which aligns with known patterns of tau deposition.

While various quantification methods for [18F]MK6240 were tested, including compartmental and reference tissue models, caution is advised in using simplified methods for high binding cases due to potential underestimation of tau levels.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of pharmacokinetic modeling strategies for in-vivo quantification of tau with the radiotracer [18F]MK6240 in human subjects. Guehl, NJ., Wooten, DW., Yokell, DL., et al.[2023]

The PET tracer 18F-PI-2620 effectively detects tau pathology in Alzheimer's disease patients, showing significantly higher binding in brain regions associated with tau deposition compared to healthy controls, indicating its potential as a diagnostic tool.

The administration of 18F-PI-2620 was found to be safe and well tolerated, with imaging results demonstrating a strong correlation between tau uptake and cognitive impairment, suggesting its utility in assessing disease severity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tau PET imaging with 18F-PI-2620 in Patients with Alzheimer Disease and Healthy Controls: A First-in-Humans Study. Mueller, A., Bullich, S., Barret, O., et al.[2022]

The novel tau-PET radiotracer [18F]PI-2620 shows strong potential as a surrogate biomarker for neuronal injury, correlating well with traditional [18F]FDG-PET imaging in a study of 26 subjects with suspected tauopathies.

Early-phase imaging of [18F]PI-2620 (0.5 to 2.5 minutes post-injection) demonstrated high agreement with [18F]FDG-PET, suggesting that it could replace the need for additional [18F]FDG-PET imaging in assessing both tau distribution and neuronal injury.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Early-phase [18F]PI-2620 tau-PET imaging as a surrogate marker of neuronal injury. Beyer, L., Nitschmann, A., Barthel, H., et al.[2022]

3H-MK6240, a second-generation tau PET tracer, shows high binding affinity for neurofibrillary tangles in Alzheimer's disease (AD) brain tissue, with significantly higher binding observed in AD patients compared to controls.

The study found that 3H-MK6240 has distinct binding characteristics compared to first-generation tau tracers, indicating its potential for more accurate detection of tau deposits in AD, particularly in early-onset cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Characterization of MK6240, a tau PET tracer, in autopsy brain tissue from Alzheimer's disease cases. Malarte, ML., Nordberg, A., Lemoine, L.[2021]

References

1. Germany pubmed.ncbi.nlm.nih.gov

Evaluation of pharmacokinetic modeling strategies for in-vivo quantification of tau with the radiotracer [18F]MK6240 in human subjects. [2023]

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

Tau PET imaging with 18F-PI-2620 in Patients with Alzheimer Disease and Healthy Controls: A First-in-Humans Study. [2022]

3. Germany pubmed.ncbi.nlm.nih.gov

Early-phase [18F]PI-2620 tau-PET imaging as a surrogate marker of neuronal injury. [2022]

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

In vivo 18F-AV-1451 tau PET signal in MAPT mutation carriers varies by expected tau isoforms. [2023]

5. Germany pubmed.ncbi.nlm.nih.gov

Characterization of MK6240, a tau PET tracer, in autopsy brain tissue from Alzheimer's disease cases. [2021]

6. Germany pubmed.ncbi.nlm.nih.gov

Dual tracer tau PET imaging reveals different molecular targets for 11C-THK5351 and 11C-PBB3 in the Alzheimer brain. [2022]