Neuroinflammation Imaging for Alzheimer's Disease

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Val Lowe

Must not be taking: NSAIDs, Corticosteroids

Disqualifiers: Pregnancy, Generalized inflammation, MRI safety, 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: 1

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine how effectively PET/CT scans can detect brain inflammation related to Alzheimer's Disease. Researchers are also examining the effects of a new imaging substance called C-11 ER176. The study suits individuals aged 60 or older who have undergone cognitive testing for about three years and have already had certain brain scans. Participants must not be taking daily anti-inflammatory drugs and should be able to remain still for 20 minutes during the scan.

As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to important advancements in Alzheimer's detection.

Will I have to stop taking my current medications?

If you are actively taking daily anti-inflammatory medications, you may need to stop, as these are generally excluded from the trial. However, a small control group may be allowed to continue. Please check with the trial coordinators for specific guidance.

What prior data suggests that this radiotracer is safe for use in PET/CT imaging?

Research shows that the new radiotracer C-11 ER176 is under study to measure brain inflammation in Alzheimer's disease. Previous studies have examined its safety in people, and early results suggest that C-11 ER176 is generally well-tolerated.

In one study, researchers used this radiotracer to image brain inflammation, and no major side effects were reported. The focus remains on ensuring the imaging is safe and accurate. While the current research phase continues to test its safety, earlier studies provide reassurance about its tolerability.

As more results emerge, the goal is to confirm these findings and ensure the tracer's safety for wider use. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about C-11 ER176 because it offers a new way to understand Alzheimer's disease by imaging neuroinflammation. Unlike current treatments, which focus on managing symptoms or slowing disease progression, C-11 ER176 is an investigational radiopharmaceutical that allows doctors to visualize inflammation in the brain using PET/CT scans. This approach provides a unique insight into the disease process, which could lead to more precise and effective treatments in the future.

What evidence suggests that this imaging method is effective for measuring brain inflammation in Alzheimer's Disease?

Research has shown that C-11 ER176, which participants in this trial will receive, effectively detects brain inflammation in Alzheimer's disease. Studies have found that it binds more effectively to inflamed brain areas than older tracers like [11C]PK11195 and [11C]PBR28, making it more reliable. The tracer aligns with brain patterns seen in Alzheimer's, aiding in identifying areas where the disease may be worsening. Early results also suggest it can detect inflammation in individuals with mild memory problems related to Alzheimer's. This indicates that C-11 ER176 could be a valuable tool for studying brain changes in Alzheimer's. ^{1 4 6 7 8}

Who Is on the Research Team?

Val Lowe, MD

Principal Investigator

Mayo Clinic

Are You a Good Fit for This Trial?

This trial is for men and women over 60 who are part of a cognitive study group, have had recent brain scans, and can consent to the study. Pregnant or breastfeeding women, those unable to lie still for scans, on daily anti-inflammatory meds, with generalized inflammation or metal in their body that affects MRI safety cannot join.

Inclusion Criteria

You need to be in one of the four groups (CU A-, CU A+, MCI A+, AD A+).

I have been undergoing cognitive tests for at least 3 years.

I can sign the consent myself or have someone legally allowed to do it for me.

Exclusion Criteria

I am not pregnant and can stop breastfeeding for 24 hours.

I cannot stay still lying down for 20 minutes.

I take daily anti-inflammatory medication.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Imaging

Participants receive a single administration of the C-11 ER176 radiotracer followed by PET/CT imaging to measure neuroinflammation

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after imaging, including assessment of adverse events

4 years

What Are the Treatments Tested in This Trial?

Interventions

• C-11 ER-176

Trial Overview Researchers are testing a new radioactive tracer called C-11 ER176 using PET/CT imaging to measure brain inflammation related to Alzheimer's Disease. They want to see if this method can help understand the disease better.

How Is the Trial Designed?

Group I: C-11 ER176 PET/CT Experimental Treatment 2 Interventions

C-11 ER176 is an investigational radiopharmaceutical that will be produced under cGMP in the Mayo Clinic Cyclotron Facility. The imaging agent (C-11 ER176) will be administered on an outpatient basis. It will be administered at a single time IV prior to the PET imaging.

Who Is Running the Clinical Trial?

Val Lowe

Lead Sponsor

Trials

1

Recruited

100+

Published Research Related to This Trial

Neuroinflammation is a key factor in the development of Alzheimer's disease, with increased glial cell activation observed in both animal models and human patients, highlighting its potential role in disease progression.

Current imaging techniques, such as positron emission tomography (PET) and magnetic resonance spectroscopy (MRS), are being explored to non-invasively detect and quantify neuroinflammation, which could improve early diagnosis and therapeutic monitoring in Alzheimer's disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

In vivo molecular imaging of neuroinflammation in Alzheimer's disease. Chaney, A., Williams, SR., Boutin, H.[2020]

The use of [11C](R)-PK11195 PET imaging allows for the detection of neuroinflammatory changes in the brain, which can be crucial for understanding various brain diseases and their progression.

This method focuses on measuring the activity of microglia, the brain's immune cells, rather than just assessing neuronal damage, highlighting its potential as a marker for disease activity in clinical settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

In vivo imaging of neuroinflammation. Cagnin, A., Gerhard, A., Banati, RB.[2019]

Molecular imaging with specific probes like (11)C-PIB and (18)F-AV-45 is crucial for the early diagnosis of Alzheimer's disease (AD) and helps evaluate the effectiveness of anti-AD therapies, which is essential given the rising number of cases.

These imaging probes not only aid in identifying the underlying biology of AD but also assist in selecting patients for clinical trials and monitoring treatment responses, potentially improving patient outcomes and guiding therapeutic decisions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Advances of molecular imaging probes for the diagnosis of Alzheimer's disease. Zhou, M., Wang, X., Liu, Z., et al.[2022]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40187909/

[11C]ER176 images brain inflammation across TSPO ... Accurately measuring brain inflammation in Alzheimer's disease (AD) is crucial due to the role of inflammatory processes in neurodegeneration.

2. clinicaltrials.gov clinicaltrials.gov/study/NCT04786223

NCT04786223 | Targeting Neuroinflammation as a ... This study is being done to research the usefulness of PET/CT imaging for measuring brain inflammation and its relation to Alzheimer's Disease. Additionally, ...

3. sciencedirect.com sciencedirect.com/science/article/pii/S0001299824000825

Emerging TSPO-PET Radiotracers for Imaging ... [11C]ER176 signal aligned with the postcentral components of the default network, reflecting the brain's topographical pattern associated with AD pathology.

4. frontiersin.org frontiersin.org/journals/immunology/articles/10.3389/fimmu.2021.739130/full

PET Imaging of Neuroinflammation in Alzheimer's Disease [11C]ER176 has demonstrated a higher binding potential and smaller variability compared to [11C]PK11195, [11C]PBR28, and [11C]DPA-713 (75, 105, 106). Clinical ...

5. academic.oup.com academic.oup.com/brain/article/148/1/119/7714867

Brain inflammation co-localizes highly with tau in mild ... We applied 11C-ER176 to detect brain inflammation in mild cognitive impairment (MCI) caused by early-onset Alzheimer's disease. Furthermore, we ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5288742/

11C-ER176, a Radioligand for 18-kDa Translocator Protein ... This study sought, first, to determine whether the sensitivity of 11C-ER176 in humans is similar to the low sensitivity measured in vitro and, ...

7. alz-journals.onlinelibrary.wiley.com alz-journals.onlinelibrary.wiley.com/doi/10.1002/alz.081801

Validating noninvasive techniques for 11C‐ER176 PET ... Noninvasive yet accurate PET quantification methods are crucial for safe yet meaningful PET studies. [11C]ER176 is a PET radioligand that images ...

8. withpower.com withpower.com/trial/phase-3-alzheimer-disease-2-2021-0235f

Neuroinflammation Imaging for Alzheimer's Disease This Phase 2 medical study run by Val Lowe needs participants to evaluate whether C-11 ER-176 will have tolerable side effects & efficacy for patients with ...