[11C]CPPC Injection for Long COVID

Overseen By Mehreen Nabi, MBBS

Age: 18+

Sex: Any

Trial Phase: Phase < 1

Sponsor: Johns Hopkins University

Must not be taking: Anti-inflammatories, Immunosuppressants, Benzodiazepines

Disqualifiers: Neurological disorders, Substance dependence, others

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

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 2

Duration: 1 day

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the safety of a new tracer (a special dye) used in PET scans, which are imaging tests that help doctors see inside the body. Researchers aim to determine if this tracer, called [11C]CPPC, can reveal differences in brain activity between individuals with lingering COVID-19 symptoms (Long COVID) and those who had COVID-19 but are now symptom-free. Participants should have contracted COVID-19 at least 6 months ago and either still experience symptoms or feel completely healthy now. As an Early Phase 1 trial, this research focuses on understanding how this new tracer works in people, offering participants the chance to contribute to this groundbreaking study.

Will I have to stop taking my current medications?

The trial requires that you stop using anti-inflammatory medications, immunosuppressants, or benzodiazepines at least 7 days before participating. If you are taking any of these, you will need to stop them temporarily.

What prior data suggests that the [11C]CPPC radiotracer is safe for PET imaging?

Research shows that [11C]CPPC is under study to assess its safety and tolerability. As this is an early research stage, detailed safety information for humans remains limited. However, reaching this stage indicates promise in earlier animal studies. Researchers are testing this substance in individuals who have had COVID-19 to determine if it can aid in imaging differences in PET scans. Importantly, participants receive only one dose, potentially reducing risks. It is crucial to note that this treatment is still under investigation, and further studies are necessary to fully understand its safety. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Unlike standard treatments for Long COVID that typically involve managing symptoms with medications like antivirals, steroids, or physical therapy, [11C]CPPC is unique because it uses a novel imaging approach. This treatment involves administering a radioactive compound, [11C]CPPC, which allows researchers to visualize the biological processes in the brain using a PET scan. This innovative method can provide insights into the underlying mechanisms of Long COVID, potentially leading to more targeted therapies in the future. Researchers are excited because this approach could reveal new information about how the condition affects the brain, opening up possibilities for more effective treatments.

What evidence suggests that this radiotracer is effective for imaging differences in Long COVID?

Research on [11C]CPPC remains in its early stages, and solid evidence of its effectiveness in treating Long COVID is not yet available. This trial will involve two groups: participants with Long COVID symptoms and healthy participants who have had COVID-19 but do not experience symptoms. Both groups will receive a single dose of [11C]CPPC, a radiotracer that highlights problem areas in scans. It is used in PET imaging, a technique that allows doctors to see how organs and tissues function inside the body. The potential of [11C]CPPC lies in its ability to show differences in brain activity between those who have had COVID-19 and still have symptoms and those who do not. This could help doctors learn more about Long COVID. However, the main goal is to determine if it is safe and can effectively highlight these differences in PET scans. ^{1 2 3 4 5}

Who Is on the Research Team?

Licia Luna, M.D., Ph.D.

Principal Investigator

Johns Hopkins University

Are You a Good Fit for This Trial?

This trial is for individuals who have had COVID-19. It's open to those with lingering symptoms (Long-COVID) and those without current symptoms. Participants must be suitable for PET scans using the [11C]CPPC radiotracer, but specific health requirements are not listed.

Inclusion Criteria

I had COVID-19 between 6 and 12 months ago.

Agrees to the visit schedule as outlined in the informed consent.

I am not pregnant and either use birth control, cannot have children, or have been menopausal for 2+ years.

Exclusion Criteria

I have a long-term brain condition like epilepsy or had a stroke.

I have had a severe head injury, stroke, seizures (except fever-related in childhood), or an abnormal brain scan.

Receipt of any investigational drug, device or biologic within 30 days of administration of study compound.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Treatment

Participants receive a single dose of [11C]CPPC intravenously followed by PET and MRI scans

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, including changes in CMP and CBC tests

2 days

1 visit (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• [11C]CPPC

Trial Overview [11C]CPPC Injection is being tested in this study. The researchers want to see if it's safe and whether it shows differences in PET scan images between Long-COVID patients and recovered individuals without symptoms.

How Is the Trial Designed?

Group I: Patients with history of COVID-19 infection and still experiencing symptoms (Long-COVID) Experimental Treatment 1 Intervention

Participants with a diagnosis of Long- COVID will receive a single dose of \[11C\]CPPC (370 megabecquerel (MBq) (X±1 mCi)) intravenously and subsequent positron emission tomography (PET) scan.

Group II: Healthy Participants with history of COVID-19 infection but not experiencing any symptoms. Experimental Treatment 1 Intervention

Healthy participants (without any history of post-COVID symptoms) will receive a single dose of \[11C\]CPPC (370 megabecquerel (MBq) (X±1 mCi)) intravenously and subsequent positron emission tomography (PET) scan.

Who Is Running the Clinical Trial?

Johns Hopkins University

Lead Sponsor

Trials

2,366

Recruited

15,160,000+

Radiological Society of North America

Collaborator

Trials

27

Recruited

1,000+

Published Research Related to This Trial

The copper-mediated radiocyanation method allows for the efficient and site-specific introduction of [11C]CN into peptides, even those with complex structures, while maintaining high radiochemical yields and minimizing side reactions.

This technique was successfully used to produce over 40 mCi of [11C]cyano-NOP, which demonstrated the ability of nociceptin to cross the blood-brain barrier and distribute throughout the brain, providing valuable insights for future research on NOP receptors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Copper-Mediated Radiocyanation of Unprotected Amino Acids and Peptides. Sharninghausen, LS., Preshlock, S., Joy, ST., et al.[2023]

The study successfully produced a significant amount of carboxyl-labeled 11C-1-aminocyclopentanecarboxylic acid (11C-ACPC) using a rapid two-step synthesis method, which could be adapted for use in various accelerator facilities.

Animal studies suggest that 11C-ACPC may serve as an effective tumor-localizing agent for cancer detection in humans through nuclear medicine imaging techniques.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Carboxyl-labeled 11C-1-aminocyclopentanecarboxylic acid, a potential agent for cancer detection. Hayes, RL., Washburn, LC., Wieland, BW., et al.[2015]

The study demonstrated that 11C-1-aminocyclopentane carboxylic acid (11C-ACPC) has a high affinity for malignant tumors, as shown by its significant uptake in VX-2 tumors in rabbits during positron emission tomography imaging.

Kinetic analysis revealed that while 11C-ACPC levels in plasma decreased rapidly post-injection, its concentration in the tumor increased over time, suggesting its potential for effective tumor detection and monitoring.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Kinetic evaluation of 11C-1-aminocyclopentane carboxylic acid in rabbits bearing VX-2 tumors using positron emission tomography. Fujiwara, T., Matsuzawa, T., Kawai, H., et al.[2023]

The study identified 11C-L-methionine as the most effective amino acid for tumor detection, showing a high uptake in cancerous tissue with a tumor to blood ratio of 11.4, indicating its potential for accurate cancer diagnosis.

11C-DL-methyl-ACPC, a newly synthesized amino acid, also demonstrated significant tumor accumulation, with a tumor to liver ratio of 3.0, suggesting it could be a valuable tool for cancer imaging using positron emission tomography.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tumor detection with carbon-11-labelled amino acids. Kubota, K., Yamada, K., Fukada, H., et al.[2019]

The study developed fluorine-containing analogs of CPPC, with one analog, Psa374, showing high potency and selectivity for the CSF1R, which is important for imaging neuroinflammation using PET scans.

While [11C]Psa374 demonstrated good uptake in monkey brains, it did not show specific binding to CSF1R at baseline, indicating that further research is needed to confirm its effectiveness for human imaging applications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Discovery of a High-Affinity Fluoromethyl Analog of [11C]5-Cyano-N-(4-(4-methylpiperazin-1-yl)-2-(piperidin-1-yl)phenyl)furan-2-carboxamide ([11C]CPPC) and Their Comparison in Mouse and Monkey as Colony-Stimulating Factor 1 Receptor Positron Emission Tomography Radioligands. Altomonte, S., Yan, X., Morse, CL., et al.[2023]

The radiotracer [11 C]CPPC can be synthesized with a high radiochemical yield of over 60 mCi and a specific activity exceeding 11,435 mCi/μmole, making it effective for use in medical applications.

The production process adheres to current Good Manufacturing Practice (cGMP) standards, ensuring that the final product is sterile and safe for human injection.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Radiosynthesis and validation of [5-cyano-N-(4-(4-[11 C]methylpiperazin-1-yl)-2-(piperidin-1-yl)phenyl) furan-2-carboxamide] ([11 C]CPPC), a PET radiotracer for imaging CSF1R, a microglia-specific marker. Mathews, WB., Wu, Y., Horti, AG., et al.[2020]

[11C] ACPC is a promising tumor-scanning agent that shows no toxic effects and can be safely administered in doses between 12 and 45 mCi, with a rapid clearance from the bloodstream allowing for effective imaging within 45 minutes.

In a study of 38 patients, [11C] ACPC scans provided valuable diagnostic information, showing 19 positive results compared to 24 positive results from traditional Ga-67 scans, suggesting its potential utility in cancer diagnosis when used with positron tomography.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tumor location with 1-aminocyclopentane [11C] carboxylic acid: preliminary clinical trials with single-photon detection. Hübner, KF., Andrews, GA., Washburn, L., et al.[2016]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06223971?term=AREA%5BInterventionSearch%5D(piperidin)%20AND%20AREA%5BStudyType%5D(INTERVENTIONAL)&rank=1

NCT06223971 | Long COVID-19 [11C]CPPC Study The goal of this study is to evaluate the safety of using the [5-cyano-N-(4-(4-[11C]Methylpiperazin-1-yl)-2-(Piperidin-1-yl)Phenyl)Furan-2-carboxamide] ([11C] ...

2. clinicaltrial.be clinicaltrial.be/en/details/422935?per_page=100&only_recruiting=0&only_eligible=0&only_active=0

Long COVID-19 [11C]CPPC Study This is a Phase 1 study of safety and tolerability of an investigational radiotracer drug called [5-cyano-N-(4-(4-[11C]Methylpiperazin-1-yl)-2-( ...

3. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/31524293/

2-(piperidin-1-yl)phenyl) furan-2-carboxamide] ([11 C]CPPC ... In this practitioner protocol, the radiochemical synthesis of [ 11 C]CPPC is described in detail, and a quality control summary of three validation ...

4. reaganudall.org reaganudall.org/clinical-trial/long-covid-19-11ccppc-study

Long COVID-19 [11C]CPPC Study The goal of this study is to evaluate the safety of using the[5-cyano-N-(4-(4-[11C]Methylpiperazin-1-yl)-2-(Piperidin-1-yl)Phenyl)Furan-2-carboxamide]([11C]CPPC ...

5. ctv.veeva.com ctv.veeva.com/study/long-covid-19-11c-cppc-study

Long COVID-19 [11C]CPPC Study - ClinicalTrials.Veeva The goal of this study is to evaluate the safety of using the [5-cyano-N-(4-(4-[11C]Methylpiperazin-1-yl)-2-(Piperidin-1-yl)Phenyl)Furan-2- ...