Imaging Agents for Alzheimer's Disease

(ADNI4 Trial)

Not currently recruiting at 59 trial locations

Overseen By ADNI Study Recruitment Team

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: University of Southern California

Must be taking: Cholinesterase inhibitors, Memantine

Must not be taking: Psychoactive medications

Disqualifiers: Neurologic disease, Major depression, Schizophrenia, Alcohol disorder, others

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

Compensation: Varies

Number of Visits: 13

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to study and validate biomarkers (measurable indicators of a condition) for Alzheimer's disease by examining clinical, cognitive, imaging, genetic, and biochemical factors. It tests multiple treatments, including Amyvid, MK-6240, NAV4694, Neuraceq, PI-2620, and Tauvid, to understand their effects on individuals with dementia, mild cognitive impairment (MCI), and those who are cognitively normal. Participants may be suitable if they have mild memory issues or have been diagnosed with Alzheimer's-related dementia. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to significant advancements in Alzheimer's treatment.

Do I need to stop taking my current medications to join the trial?

You may need to stop certain medications, especially psychoactive ones, for at least 4 weeks before joining the trial. Some medications like antidepressants without anticholinergic effects, estrogen replacement, and Gingko biloba are allowed if stable. Specific Alzheimer's treatments need to be stable for a longer period before screening.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

In a previous study, researchers tested Amyvid in 555 adults and generally found it to be safe. Some participants reported mild headaches and reactions at the injection site, but these were uncommon. The FDA has also approved Amyvid for other uses, which adds confidence in its safety.

Research on MK-6240 has shown it to be safe for participants, with no major side effects reported, suggesting it is well-tolerated.

NAV4694 was studied in individuals, including those with mild cognitive issues, and was found to be safe with no serious side effects.

Researchers evaluated Neuraceq in 872 adults. Most participants tolerated it well, with only a few experiencing mild reactions like headaches or dizziness. It is also FDA-approved for other uses, supporting its safety.

PI-2620 was tested in 22 people, and no adverse effects were reported, indicating it is well-tolerated.

Tauvid is FDA-approved for imaging in adults with cognitive issues. Studies showed only mild side effects, which were considered acceptable.

Overall, studies have shown these treatments to be safe, with only minor and uncommon side effects. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about these treatments for Alzheimer's disease because they represent a new wave of diagnostic tools utilizing advanced imaging agents. While traditional methods focus on symptom management or target amyloid plaques, these agents—like Amyvid, MK-6240, and Tauvid—are used in PET scans to visualize amyloid and tau proteins in the brain. This precise imaging helps to better understand and diagnose the disease, potentially leading to earlier and more personalized treatment approaches. Unlike current treatments that manage symptoms, these innovative imaging agents aim to enhance diagnosis and tracking, which could revolutionize how Alzheimer's is treated in the future.

What evidence suggests that this trial's treatments could be effective for Alzheimer's disease?

This trial will evaluate various imaging agents to understand and track Alzheimer's disease progression through advanced imaging techniques. Studies have shown that Amyvid, one of the imaging agents in this trial, helps identify the risk of memory and thinking problems in people with mild memory issues and older adults without symptoms. MK-6240, another agent under study, effectively tracks the buildup of tau protein, which is linked to Alzheimer's disease and related to memory problems. NAV4694 imaging results are similar to other well-known brain scans for early Alzheimer's detection, suggesting reliability. Neuraceq has improved the diagnosis of memory and thinking issues by identifying brain plaques associated with Alzheimer's. PI-2620 detects tau protein levels in the brain, aiding in the diagnosis of memory decline. Lastly, Tauvid scans predict future memory problems by identifying patterns of tau protein. Each of these methods is being tested in this trial to help understand and track Alzheimer's disease progression. ^{6 7 8 9 10}

Who Is on the Research Team?

Michael Weiner, MD

Principal Investigator

University of California, San Francisco

Paul Aisen, MD

Principal Investigator

USC Alzheimer's Therapeutic Research Institute (ATRI)

Ronald Petersen, MD, PHD

Principal Investigator

Mayo Clinic

Are You a Good Fit for This Trial?

Inclusion Criteria

Participant may or may not have a significant subjective memory concern as reported by participant, study partner, or clinician.

≥9 for 16 or more years of education

≥ 5 for 8-15 years of education

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Baseline/Initial Assessment

Participants undergo initial clinical and cognitive assessments, including imaging and biomarker tests

1-2 months

1-2 visits (in-person)

Longitudinal Assessment

Participants undergo repeated clinical and cognitive assessments, imaging, and biomarker tests over time

5 years

Multiple visits (in-person) at months 12, 24, 36, and 48

Follow-up

Participants are monitored for safety and effectiveness after the main assessment period

6 months

What Are the Treatments Tested in This Trial?

Interventions

• Amyvid
• MK-6240
• NAV4694
• Neuraceq
• PI-2620
• Tauvid

How Is the Trial Designed?

Group I: Mild Cognitive Impairment (MCI) Experimental Treatment 6 Interventions

450 participants with mild cognitive impairment (MCI), which is anticipated to include 250 newly enrolled participants and 200 rollover participants from the prior ADNI3 study with MCI.

Group II: Dementia (DEM) Experimental Treatment 6 Interventions

350 participants with mild dementia (DEM), which is anticipated to include 250 newly enrolled participants and 100 participants followed from the prior ADNI3 study with dementia.

Group III: Cognitively Normal (CN) Experimental Treatment 6 Interventions

700 participants with no apparent memory problems, which is anticipated to include 250 newly enrolled participants and 450 rollover participants from the prior ADNI3 study without apparent memory problems.

Who Is Running the Clinical Trial?

University of Southern California

Lead Sponsor

Trials

956

Recruited

1,609,000+

Alzheimer's Therapeutic Research Institute

Collaborator

Trials

18

Recruited

58,400+

National Institute on Aging (NIA)

Collaborator

Trials

1,841

Recruited

28,150,000+

Northern California Institute of Research and Education

Collaborator

Trials

30

Recruited

10,400+

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8349062/

Five-year outcomes after IVIG for mild cognitive impairment ... The purpose of this study was to assess the five-year treatment effects of a short course of intravenous immunoglobulin (IVIG) in subjects ...

2. nature.com nature.com/articles/mp20149

Florbetapir F 18 amyloid PET and 36-month cognitive ... Our results suggest that amyloid PET has promise for detecting risk of subsequent cognitive decline in patients with MCI and CN older adults, ...

3. jnm.snmjournals.org jnm.snmjournals.org/content/61/4/597

Predictive Value of 18F-Florbetapir and 18F-FDG PET for ... Comparison of visual and quantitative florbetapir F 18 positron emission tomography analysis in predicting mild cognitive impairment outcomes.

4. molecularneurodegeneration.biomedcentral.com molecularneurodegeneration.biomedcentral.com/articles/10.1186/1750-1326-9-10

A consecutive case series experience with [18 F] florbetapir ... estimate brain amyloid burden in patients being evaluated for cognitive impairment or dementia. Imaging with [18 F] florbetapir offers in ...

5. link.springer.com link.springer.com/article/10.1007/s12149-022-01792-y

Clinical impact of amyloid PET using 18 F-florbetapir in ... The amyloid PET results changed the AD and non-AD diagnosis in 39 of 99 patients (39.3%). The change rates of 26 of the 54 patients (48.1%) with ...

6. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2025/202008s046lbl.pdf

AMYVID (florbetapir F 18 injection), for intravenous use The safety of AMYVID was evaluated in 555 adult subjects ... dementing disorder, 5 had mild cognitive impairment (MCI), and 12 had no cognitive impairment.

7. amyvid.lilly.com amyvid.lilly.com/hcp/amyvid-scan

Amyvid Scan | Amyvid® (Florbetapir F 18 Injection) - Eli Lilly Find information on the reliability, accuracy and reproducibility of Amyvid in estimating amyloid beta neuritic plaque density.

8. ema.europa.eu ema.europa.eu/en/documents/product-information/amyvid-epar-product-information_en.pdf

Amyvid, INN-florbetapir [18F] - European Medicines Agency For the limitations of use in patients with mild cognitive impairment (MCI), see section 5.1. ... 5.3 Preclinical safety data. Animal toxicology and safety ...

9. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2012/202008s000lbl.pdf

Amyvid (Florbetapir F 18 Injection) for intravenous use HIGHLIGHTS OF PRESCRIBING INFORMATION. These highlights do not include all the information needed to use Amyvid safely and effectively.

10. jnm.snmjournals.org jnm.snmjournals.org/content/early/2025/01/07/jnumed.124.268756

Updated Appropriate Use Criteria for Amyloid and Tau PET Three fluorine-18 Aβ agents are approved by the U.S. FDA, European Medicines Agency, and other global regulatory agencies for clinical use “to ...