FNP-59 for High Cholesterol

Overseen By Benjamin Viglianti, M.D, Ph.D.

Age: 18+

Sex: Any

Trial Phase: Phase < 1

Sponsor: Benjamin Viglianti

Must not be taking: Steroids, OCP, Spironolactone, others

Disqualifiers: Pregnancy, Adrenal pathology, others

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

Compensation: Varies

Number of Visits: 1

6 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to test a new imaging agent, [18F]FNP-59, to evaluate its effectiveness in visualizing the adrenal glands using PET scans. Researchers hope this agent will provide clearer images and reduce radiation exposure. The trial seeks individuals who are generally healthy, have no known adrenal issues, and are not currently taking medications such as steroids or hormone-based treatments. As an Early Phase 1 trial, participants will be among the first to help researchers understand how this new imaging agent functions in people.

Will I have to stop taking my current medications?

Yes, you will need to stop taking certain medications like steroids, oral contraceptives, spironolactone, estrogen, androgen, progesterone, ACE inhibitors, ARBs, or hormone analogue supplements to participate in this trial.

What prior data suggests that [18F]FNP-59 is safe for imaging the adrenal gland?

Research has shown that [18F]FNP-59 has a good safety record in early studies. These studies found that [18F]FNP-59 functions like an older imaging agent but with improved safety. Tests on living organisms confirmed that [18F]FNP-59 was safe at the planned dose, causing no harm when used as intended.

Overall, the findings suggest that [18F]FNP-59 is well-tolerated at the doses being tested. Since this is an early trial, more research is needed to confirm these results. However, current data indicates that [18F]FNP-59 is safe to use in the small doses being tested. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Most treatments for high cholesterol, like statins, work by reducing the liver's production of cholesterol or helping the body remove it. But [18F]FNP-59 is unique because it uses a radiotracer to map cholesterol distribution in the body, offering a new way to understand how cholesterol is processed. This approach could help tailor treatments to individual patients by providing personalized insights into their cholesterol metabolism. Researchers are excited about this treatment because it could lead to more precise and effective management of high cholesterol, potentially improving outcomes for patients who do not respond well to traditional therapies.

What evidence suggests that this imaging technique is effective for high cholesterol?

Research has shown that [18F]FNP-59 could offer a promising new method for imaging the adrenal glands. Studies have found that this imaging agent can produce clearer images while exposing patients to less radiation. The fluorine-18 version of NP-59 mimics cholesterol, aiding in visualizing adrenal gland function. In animal studies, this agent behaved like the older NP-59 but proved safer due to reduced radiation. These early findings suggest it could lead to better and safer imaging of cholesterol use in the body. Participants in this trial will receive [18F]FNP-59 to determine normal tissue distribution and confirm calculated radiation dosimetry and optimal uptake time. ^{1 2 3 4 5}

Who Is on the Research Team?

Ben Viglianti, M.D, Ph.D.

Principal Investigator

University of Michigan

Are You a Good Fit for This Trial?

This trial is for healthy individuals without any adrenal gland issues. They must not be pregnant, imprisoned, or unable to consent. Participants should not be on steroids, certain blood pressure medications (ACE inhibitors/ARBs), hormone treatments like oral contraceptives, or weigh over 400 lbs.

Inclusion Criteria

My adrenal glands are healthy and I have no known adrenal diseases.

Exclusion Criteria

Pregnancy

I cannot undergo imaging tests.

I have a diagnosed adrenal gland condition.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Imaging

Participants receive a sub-therapeutic dose of [18F]FNP-59 for PET imaging to evaluate cholesterol trafficking in the adrenal gland

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after imaging

1-2 weeks

What Are the Treatments Tested in This Trial?

Interventions

• [18F]FNP-59

Trial Overview [18F]FNP-59 is being tested as a new PET imaging agent that could potentially provide clearer images of the adrenal glands with less radiation exposure compared to current methods. This phase 0 study involves a single sub-therapeutic dose in normal subjects.

How Is the Trial Designed?

Group I: Group 1 Experimental Treatment 1 Intervention

These subjects, 6 planned (3 male, 3 female), will be to obtain normal tissue distribution of \[18F\]NP-59 and confirm calculated radiation dosimetry and optimal uptake time.

Who Is Running the Clinical Trial?

Benjamin Viglianti

Lead Sponsor

Trials

2

Recruited

30+

Published Research Related to This Trial

In a study of 24 patients with familial hypercholesterolemia over 104 weeks, fluvastatin significantly reduced total cholesterol by 26.8% and LDL cholesterol by 33.1%, demonstrating its efficacy in managing high cholesterol levels.

The treatment also led to a 35% reduction in the LDL-C: HDL-C ratio, indicating improved cholesterol balance, while increases in HDL cholesterol were observed, although they were variable.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical efficacy of fluvastatin in the long-term treatment of familial hypercholesterolemia. Koizumi, J., Haraki, T., Yagi, K., et al.[2019]

Fluvastatin effectively lowers LDL cholesterol levels by 22-31% in patients with severe primary hypercholesterolemia and by 19-25% in those with familial hypercholesterolemia, demonstrating its efficacy as a cholesterol-lowering medication.

Fluvastatin is a cost-effective option for managing hypercholesterolemia, priced 40% lower than other statins, and has a favorable safety profile with manageable side effects, including reversible increases in liver enzymes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A review of current clinical findings with fluvastatin. Garnett, WR.[2019]

PCSK9 monoclonal antibodies (mAbs) significantly reduced LDL cholesterol levels by an average of 49.14% in patients with familial hypercholesterolemia, based on a meta-analysis of 7 clinical trials involving 926 patients.

The treatment was found to be safe, with no significant differences in common or serious adverse events compared to placebo, indicating good tolerability for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Systematic Review and Meta-Analysis of Therapeutic Efficacy and Safety of Alirocumab and Evolocumab on Familial Hypercholesterolemia. Ge, X., Zhu, T., Zeng, H., et al.[2022]

In a study of 423 hypercholesterolemic patients, 6 weeks of treatment with fluvastatin significantly reduced harmful lipoprotein particles (apo B, LpE:B, and LpC-III:B) compared to placebo, indicating its efficacy in improving lipid profiles.

Fluvastatin treatment also led to increases in beneficial lipoproteins (apo A-I and LpA-I), suggesting that it not only lowers bad cholesterol but also enhances protective factors against coronary artery disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fluvastatin reduces levels of plasma apo B-containing particles and increases those of LpA-I. European Fluvastatin Study Group. Dallongeville, J., Fruchart, JC., Pfister, P., et al.[2019]

In a study of 38 patients with heterozygous familial hypercholesterolemia, the combination of fluvastatin and bezafibrate was more effective than fluvastatin and cholestyramine in reducing LDL cholesterol levels and improving the LDL-C/HDL-C ratio after 6 weeks of treatment.

Both drug combinations significantly lowered LDL cholesterol compared to fluvastatin alone, with no reported cases of myositis, indicating a favorable safety profile for these treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of a combination fluvastatin-bezafibrate treatment for familial hypercholesterolemia: comparative analysis with a fluvastatin-cholestyramine combination. Leitersdorf, E., Muratti, EN., Eliav, O., et al.[2019]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9730927/

Development of Fluorinated NP-59: A Revival of Cholesterol ... The goal of this study was to prepare and evaluate a 18 F analog of NP-59 to serve as a PET imaging agent for functional imaging of the adrenal glands based on ...

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/35483964/

Development of Fluorinated NP-59: A Revival of Cholesterol ... Conclusion: 18F-FNP-59 provided higher resolution images, with lower radiation dose to the subjects. It has the potential to provide a noninvasive test for ...

3. centerwatch.com centerwatch.com/clinical-trials/listings/NCT04546126/positron-emission-tomography-pet-imaging-of-cholesterol-trafficking-clinical-evaluation-of-18ffnp-59-in-normal-human-subjects-groups-2-3-4

Clinical Evaluation of [18F]FNP-59 in Normal Human ... This study will evaluate the feasibility of using a sub-therapeutic dose of a fluorine-18 analogue of NP-59 ([18F]FNP-59) to image the adrenal ...

4. ctv.veeva.com ctv.veeva.com/study/positron-emission-tomography-pet-imaging-of-cholesterol-trafficking-clinical-evaluation-of-18f-f

Clinical Evaluation of [18F]FNP-59 in Normal Human Subjects ... The researchers believe that [18F]FNP-59 would greatly improve the imaging characteristics, by providing a PET imaging cholesterol analogue with ...

5. researchgate.net researchgate.net/publication/360289686_Development_of_Flourinated_NP-59_A_Revival_of_Cholesterol_Utilization_Imaging_with_PET

A Revival of Cholesterol Utilization Imaging with PET Biodistribution studies with 18F-FNP-59 demonstrated a similar pharmacokinetic profile to NP-59, but with decreased radiation exposure. In vivo animal images ...