Brain Imaging for Post-Heart Attack Inflammation

Overseen By Jonathan McConathy, MD, PhD

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: University of Alabama at Birmingham

Disqualifiers: Pregnancy, Dementia, Major depression, others

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

Approved in 2 Jurisdictions This treatment is already approved in other countries

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 if a special PET/MRI brain scan with the new drug [18F]DPA-714 can detect brain inflammation after a heart attack. Understanding this inflammation could help doctors develop better methods to protect the brain in heart disease patients. The trial seeks individuals who recently had a heart attack treated at UAB Hospital or are scheduled for a heart procedure there. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new drug.

Do I need to stop my current medications for this trial?

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.

What prior data suggests that PET/MRI with [18F]DPA-714 is safe for brain imaging?

Research has shown that [18F]DPA-714 is still undergoing safety testing in humans. Some studies have used it to visualize inflammation in the body, particularly in the brain. These studies aim to assess its effectiveness in detecting inflammation.

In animal studies, [18F]DPA-714 demonstrated varying levels of activity in healthy versus diseased tissues, suggesting it behaves differently depending on the tissue. However, detailed safety information for humans remains incomplete. This trial is in an early phase, primarily focusing on assessing the treatment's safety.

Since this is an early stage of testing, the treatment's safety is still under investigation. Participants in such trials help researchers gather more information about the treatment's safety and effectiveness. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about [18F]DPA-714 because it offers a fresh approach to understanding post-heart attack inflammation. Unlike traditional treatments that focus on managing symptoms or preventing further heart damage, [18F]DPA-714 is a radiotracer used in brain imaging that targets inflammation directly. This allows for detailed visualization of inflammatory processes, potentially leading to better-tailored treatments. By providing insights into how inflammation affects the brain after a heart attack, this approach could pave the way for more precise and effective therapies in the future.

What evidence suggests that PET/MRI with [18F]DPA-714 is effective for detecting brain inflammation after a heart attack?

Studies have shown that the investigational drug [18F]DPA-714 effectively detects brain inflammation, which significantly impacts many diseases. In previous research, [18F]DPA-714 successfully highlighted brain inflammation in PET scans. This trial involves participants who recently experienced a myocardial infarction or are undergoing elective percutaneous coronary intervention. The imaging helps researchers understand how inflammation affects the brain after a heart attack. Initial tests in healthy individuals suggest that [18F]DPA-714 is a useful tool for identifying brain inflammation. This could potentially lead to better treatments to protect the brain after heart problems. ^{1 4 6 7 8}

Are You a Good Fit for This Trial?

This trial is for adults over 21 who've had a recent heart attack treated with PCI or are undergoing elective PCI. They must speak English, have at least an 8th-grade education, and be genetically predisposed to brain inflammation after a heart attack. People can't join if they're pregnant, breastfeeding, have serious health issues that could affect participation, history of severe head injury, major depression or dementia.

Inclusion Criteria

I am admitted to UAB Hospital for a severe heart attack and treated with PCI, or I am undergoing elective PCI.

I am 21 years old or older.

Participation in UAB IRB protocol 'Neuroinflammation After Acute Myocardial Infarction' (IRB-300002751, PI Lazar)

Exclusion Criteria

I have had heart bypass surgery in the past.

You have had a serious head injury that caused you to lose consciousness for more than 30 minutes or have a seizure.

I have had a heart attack before.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Imaging

Participants undergo PET/MRI imaging to measure neuroinflammation using the investigational drug [18F]DPA-714

1-2 weeks

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after imaging

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• [18F]DPA-714

Trial Overview The study tests whether PET/MRI scans using the investigational drug [18F]DPA-714 can detect brain inflammation following a heart attack. This research aims to understand how heart disease affects the brain and may lead to new protective treatments.

How Is the Trial Designed?

Group I: undergoing elective percutaneous coronary intervention Experimental Treatment 1 Intervention

Group II: Recent Myocardial Infarction Experimental Treatment 1 Intervention

Who Is Running the Clinical Trial?

University of Alabama at Birmingham

Lead Sponsor

Trials

1,677

Recruited

2,458,000+

Published Research Related to This Trial

The study developed a molecular imaging probe, [18F]DPA714, which effectively targets the 18-kDa translocator protein (TSPO) to monitor microglia activation and neuroinflammation in an Alzheimer's disease mouse model, showing a significant increase in uptake in affected brain regions compared to control mice.

Quantitative PET imaging revealed that [18F]DPA714 uptake was significantly higher in the cortex and hippocampus of APP/PS1 mice at 12-13 and 15-16 months of age, indicating its potential utility in determining optimal timing for anti-inflammatory therapies in Alzheimer's disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

PET Imaging for Dynamically Monitoring Neuroinflammation in APP/PS1 Mouse Model Using [18F]DPA714. Hu, W., Pan, D., Wang, Y., et al.[2020]

The new radiotracer [18F]F-DPA was successfully synthesized and showed a high radiochemical purity of over 99%, indicating its potential for reliable use in imaging neuroinflammation.

In comparison to the related radiotracer [18F]DPA-714, [18F]F-DPA demonstrated a significantly higher stability in vivo, with 93.5% of the radioactivity remaining unchanged in the brain, suggesting it may be more effective for imaging neurological conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Radiosynthesis and Preclinical Evaluation of [18F]F-DPA, A Novel Pyrazolo[1,5a]pyrimidine Acetamide TSPO Radioligand, in Healthy Sprague Dawley Rats. Keller, T., Krzyczmonik, A., Forsback, S., et al.[2023]

In a mouse model of stroke, treatment with AMD3100 significantly reduced neuroinflammation, as indicated by decreased TSPO levels measured through PET imaging, suggesting its potential as an anti-inflammatory therapy.

The study utilized a combination of in vivo PET scans and ex vivo histological analysis to confirm the effectiveness of AMD3100 in reducing inflammation, demonstrating the utility of TSPO-targeted imaging in evaluating treatment efficacy after ischemic brain injury.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[(18)F]DPA-714 PET imaging of AMD3100 treatment in a mouse model of stroke. Wang, Y., Yue, X., Kiesewetter, DO., et al.[2021]

Citations

1. centerwatch.com centerwatch.com/clinical-trials/listings/NCT03968445/neuroinflammation-after-myocardial-infarction-imaging-substudy

Neuroinflammation After Myocardial Infarction - Imaging ... ... imaging (PET/MRI) with an investigational drug called [18F]DPA-714 will show inflammation in the brain after a heart attack. This study may ...

2. sciencedirect.com sciencedirect.com/science/article/pii/S1936878X18305576

Molecular Imaging of Myocardial Inflammation With ... Preliminary experience with 18F-labeled fluorodeoxyglucose ([18F]FDG) demonstrates localized inflammatory cell signal within the infarct territory as an ...

3. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40441893/

Whole-Body [18F]DPA-714 Kinetic Assessment Using PET ... Multisystemic inflammation might be a key pathophysiologic mechanism in post-coronavirus disease 2019 (post-COVID) syndrome.

4. researchgate.net researchgate.net/publication/51882405_Initial_evaluation_in_healthy_humans_of_F-18DPA-714_a_potential_PET_biomarker_for_neuroinflammation

Initial evaluation in healthy humans of [F-18]DPA-714, a ... It is thereby a suitable in vivo biomarker of neuroinflammation for detection, evaluation and therapeutic monitoring of brain diseases. We aimed ...

5. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/29717383/

[18F]DPA-714 PET imaging shows immunomodulatory ... The [18F]DPA-714 PET/CT system can accurately demonstrate brain inflammation and evaluate the BMSC therapeutic effect in an imaging context.

6. jacc.org jacc.org/doi/10.1016/j.jcmg.2018.05.026

Molecular Imaging of Myocardial Inflammation With ... Preliminary experience with 18F-labeled fluorodeoxyglucose ([18F]FDG) demonstrates localized inflammatory cell signal within the infarct ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5956996/

In vivo imaging biomarkers of neuroinflammation in the ... Fortasyn-fed mice showed a reduced uptake of [18F]DPA-714 in the infarction after 35 days. (B) Comparison of [18F]DPA-714 with TSPO immunohistochemistry.

8. pubs.acs.org pubs.acs.org/doi/10.1021/acs.jmedchem.7b00374

Development of a 18 F-Labeled Radiotracer with Improved ... Results: [18F]DPA-714 showed different uptake levels in healthy organs and malignant tissues of mice and rats. Although high and displaceable [18F]DPA-714 ...