11C-ER176 for Alzheimer's Disease

Overseen By Alireza Faridar

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: The Methodist Hospital Research Institute

Must be taking: Acetylcholinesterase inhibitors, Memantine

Must not be taking: Antipsychotics, Antiepileptics, Corticosteroids, others

Disqualifiers: Infections, Cardiac dysfunction, Cancer, others

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

Compensation: Varies

Number of Visits: 2

Duration: 22 weeks

40 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how a treatment might reduce brain inflammation in people with Alzheimer's disease. Researchers aim to determine if a low dose of interleukin-2 (IL-2), administered every 2 or 4 weeks, affects inflammation markers in the blood and spinal fluid. Participants will receive either IL-2 at varying frequencies or a placebo for comparison. Suitable candidates have an Alzheimer's diagnosis and are on a stable dose of Alzheimer's medication. As a Phase 2 trial, this research focuses on assessing the treatment's effectiveness in an initial, smaller group.

Will I have to stop taking my current medications?

The trial requires that participants stay on a stable dosage of Alzheimer's medications (like rivastigmine, galantamine, donepezil, memantine) for at least 4 weeks before screening and throughout the study. Other chronic medications must also be stable for at least 30 days before screening. Some medications, like certain antipsychotics and antiepileptics, are not allowed during the study.

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

Research shows that 11C-ER176 helps capture images of brain inflammation, aiding in the understanding of Alzheimer's disease. Although past studies provide limited information about its safety, 11C-ER176 serves as an imaging tool rather than a typical drug.

The trial also involves low-dose interleukin-2 (IL-2) treatment. IL-2, or aldesleukin, has FDA approval for treating certain cancers, indicating prior safety testing in humans. However, doses and conditions may differ in this trial, and new conditions might present unknown side effects.

Prospective participants should know that studies, especially in this phase, closely monitor safety. Discuss potential risks with the clinical trial team. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Unlike the standard treatments for Alzheimer's Disease, which often focus on managing symptoms, 11C-ER176 is unique because it uses a new mechanism to target inflammation in the brain. This approach could address one of the underlying causes of Alzheimer's rather than just alleviating its symptoms. Researchers are excited about 11C-ER176 because it represents a potential breakthrough in how we understand and treat this complex condition. By directly targeting the inflammation, this treatment might slow down or even alter the disease's progression, offering hope for more effective management of Alzheimer's.

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

Research shows that 11C-ER176 is a special substance used in PET scans to detect brain inflammation related to Alzheimer's disease. Studies have found that it clearly reveals this inflammation, a key aspect of Alzheimer's. This insight aids in understanding how inflammation impacts the disease and might assist in early detection. 11C-ER176 remains stable in the blood, making it a reliable tool for brain imaging. While primarily used for brain imaging, this detailed view of inflammation could be crucial for future treatments. ^{3 4 5 6 7}

Are You a Good Fit for This Trial?

This trial is for individuals with Alzheimer's Disease. It aims to explore the role of inflammation in AD by measuring biomarkers in blood and CSF, and brain glial activation via PET scans. Participants will also receive low-dose IL-2 immunotherapy over 22 weeks.

Inclusion Criteria

My INR is below 1.4 and I've been on a stable dose of my cognition medication for 4 weeks.

Alanine aminotransferase level (ALT) and aspartate aminotransferase (AST) less than or equal to two times normal

Formal education of eight or more years

Exclusion Criteria

Suspected or known allergy to any components of the study treatments

Any condition, which in the opinion of the investigator makes the patient unsuitable for inclusion

I am not taking certain medications during the study.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive low-dose interleukin-2 (IL-2) immunotherapy to assess its effect on inflammation biomarkers

22 weeks

Visits every 2 or 4 weeks depending on group assignment

Follow-up

Participants are monitored for safety and effectiveness after treatment, including measurement of brain glial activation and inflammation biomarkers

36 months

What Are the Treatments Tested in This Trial?

Interventions

• 11C-ER176

Trial Overview The study tests how a marker called 11C-ER176 used in PET scans can show brain inflammation. Additionally, it examines the effects of a treatment with low-dose interleukin-2 on inflammation markers in patients with Alzheimer's Disease.

How Is the Trial Designed?

Group I: IL-2 every 2 weeks Active Control 1 Intervention

Aldesleukin every 2 weeks

Group II: IL-2 every 4 weeks Active Control 1 Intervention

Aldesleukin every 4 weeks

Group III: Placebo Placebo Group 1 Intervention

Who Is Running the Clinical Trial?

The Methodist Hospital Research Institute

Lead Sponsor

Trials

299

Recruited

82,500+

Published Research Related to This Trial

The study used [(11)C]BF-227 PET imaging to identify early brain changes in patients with mild cognitive impairment (MCI), revealing that abnormal BF-227 distribution in the lateral temporal cortex can predict progression to Alzheimer's disease (AD).

BF-227 uptake was strongly correlated with the density of amyloid-β plaques in the brain, indicating its potential as a reliable biomarker for identifying MCI patients at risk of converting to AD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Voxel-based analysis of amyloid positron emission tomography probe [C]BF-227 uptake in mild cognitive impairment and alzheimer's disease. Shao, H., Okamura, N., Sugi, K., et al.[2016]

The novel PET tracer 18F-RO-948 shows superior binding characteristics for detecting tau pathology in Alzheimer's disease compared to other tracers 11C-RO-963 and 11C-RO-643, based on human evaluations involving amyloid PET-positive AD subjects and healthy controls.

In the study, 18F-RO-948 effectively discriminated between Alzheimer's patients and healthy individuals, revealing significant differences in tau accumulation across multiple brain regions, indicating its potential as a valuable tool for diagnosing and understanding Alzheimer's disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Characterization of 3 Novel Tau Radiopharmaceuticals, 11C-RO-963, 11C-RO-643, and 18F-RO-948, in Healthy Controls and in Alzheimer Subjects. Wong, DF., Comley, RA., Kuwabara, H., et al.[2019]

In a study of 166 subjects with varying cognitive abilities, early-phase amyloid-PET scans (using 18F-florbetapir or 18F-flutemetamol) showed strong positive correlations with 18F-FDG-PET scans, indicating that they can effectively assess both amyloid deposition and neurodegeneration in Alzheimer's disease.

The early-phase amyloid-PET imaging demonstrated comparable ability to discriminate Alzheimer's patients from healthy controls, suggesting it could replace 18F-FDG-PET imaging in clinical practice, potentially reducing costs while maintaining diagnostic accuracy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Early-phase 18F-Florbetapir and 18F-Flutemetamol images as proxies of brain metabolism in a memory clinic setting. Boccalini, C., Peretti, DE., Ribaldi, F., et al.[2023]

The novel compound [18F] JNJ-64326067 shows promise for detecting tau aggregates in the brain, with significant retention observed in 4 out of 5 participants with probable Alzheimer's disease, indicating its potential efficacy in identifying neurodegenerative changes.

The dosimetry results suggest that [18F] JNJ-64326067 has a low effective dose for both males and females, making it a safe option for imaging tau pathology in clinical settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical evaluation of [18F] JNJ-64326067, a novel candidate PET tracer for the detection of tau pathology in Alzheimer's disease. Schmidt, ME., Janssens, L., Moechars, D., et al.[2021]

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]

Citations

1. 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, ...

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

Neuroinflammation Imaging for Alzheimer's Disease What data supports the effectiveness of the drug C-11 ER-176 for Alzheimer's disease? The research highlights the importance of imaging neuroinflammation in ...

3. frontiersin.org frontiersin.org/journals/aging-neuroscience/articles/10.3389/fnagi.2021.624330/full

PET Neuroimaging of Alzheimer's Disease: Radiotracers ... In this article we survey the various PET radiotracers available for AD imaging and discuss their clinical applications especially in terms of early detection ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT03958630

PET Imaging of Neuroinflammation in Neurodegenerative ... To see if the drug [11C]ER176 can show inflammation in the brain in people with certain progressive neurological disorders compared to healthy adults. Also to ...

5. researchgate.net researchgate.net/publication/333518986_Head-to-head_comparison_of_11C-PBR28_and_11C-ER176_for_quantification_of_the_translocator_protein_in_the_human_brain

Head-to-head comparison of 11C-PBR28 and 11C-ER176 ... Results ¹¹C-ER176 was more stable in arterial blood than ¹¹C-PBR28 (the percentages of unmetabolized parent in plasma at 90 min were 29.0 ± 8.3% and 8.8 ± 2.9% ...

6. 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.

7. researchgate.net researchgate.net/publication/310585749_11C-ER176_a_radioligand_for_18-kDa_translocator_protein_TSPO_has_adequate_sensitivity_to_robustly_image_all_three_affinity_genotypes_in_human_brain

(PDF) 11C-ER176, a radioligand for 18-kDa translocator ... 11C-ER176, a radioligand for 18-kDa translocator protein (TSPO), has adequate sensitivity to robustly image all three affinity genotypes in human brain.