Oral Hymecromone for Primary Sclerosing Cholangitis

(HAAPS Trial)

Recruiting at 1 trial location

Age: Any Age

Sex: Any

Trial Phase: Phase 2

Sponsor: Aparna Goel

Must not be taking: Biologics

Disqualifiers: Cholangiocarcinoma, Pregnancy, Serious liver disease, 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

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

Compensation: Varies

Number of Visits: Unknown

Duration: 6 months

24 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called hymecromone for individuals with primary sclerosing cholangitis (PSC), a liver condition affecting bile ducts. Researchers aim to determine if hymecromone, when added to regular treatments, can manage PSC more effectively than standard care alone. They will also assess hymecromone's impact on disease indicators such as liver stiffness and inflammation levels. Individuals with a confirmed PSC diagnosis who are not currently on biologic therapies may be suitable for this trial. Participants will either receive hymecromone alongside their usual care for six months or continue with their standard care. As a Phase 2 trial, this research focuses on evaluating the treatment's effectiveness in an initial, smaller group of people.

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

The trial does not specify if you need to stop taking your current medications, but it does require that you are not currently receiving biologic therapies. If you have inflammatory bowel disease, your treatment must be stable for at least 6 months.

Is there any evidence suggesting that hymecromone is likely to be safe for humans?

Research has shown that hymecromone reduces inflammation in the body, which is crucial because inflammation can worsen conditions like primary sclerosing cholangitis (PSC), a liver disease. Early findings suggest hymecromone is generally safe for patients, with only some mild side effects reported, though they are uncommon.

This trial is in the middle phase of testing, indicating that the treatment has already passed initial safety checks. This phase focuses on assessing the treatment's effectiveness and further confirming its safety. Although the FDA has not approved hymecromone for PSC, its use in other conditions provides researchers with some confidence in its safety. As with any treatment, participants should discuss potential risks with their healthcare providers. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for primary sclerosing cholangitis, which generally focus on managing symptoms and complications, Hymecromone offers a new approach by potentially reducing bile duct inflammation. This treatment is unique because it targets the production of hyaluronic acid, a substance associated with inflammation in this condition. Researchers are excited about Hymecromone because its mechanism of action could address the disease's underlying inflammation more directly, potentially leading to better outcomes for patients.

What evidence suggests that hymecromone might be an effective treatment for primary sclerosing cholangitis?

Research suggests that hymecromone might help treat Primary Sclerosing Cholangitis (PSC) by reducing inflammation. It lowers hyaluronan levels, a substance that increases with chronic inflammation and is linked to PSC. Early studies indicate that hymecromone could improve liver function by decreasing inflammation and possibly slowing the disease's progression. In this trial, some participants will receive hymecromone alongside standard care to further investigate its potential benefits. While the evidence is promising, more research is needed to fully understand its benefits for people with PSC. ^{1 2 4 6 7}

Who Is on the Research Team?

Aparna Goel, MD

Principal Investigator

Stanford University

Leina Alrabadi, MD

Principal Investigator

Stanford University

Are You a Good Fit for This Trial?

This trial is for adolescents and adults with confirmed primary sclerosing cholangitis (PSC). Participants should have stable inflammatory bowel disease if present, normal inflammation markers, and consistent non-excluded medication for at least 6 months. Those on biologics, pregnant individuals, people with serious liver issues or cholangiocarcinoma, or allergies to hymecromone can't join.

Inclusion Criteria

My inflammatory bowel disease is stable, with normal markers and no changes in treatment for 6 months.

My liver condition was confirmed by a biopsy or imaging.

Exclusion Criteria

I have a serious liver condition.

Pregnancy

I have been diagnosed with cholangiocarcinoma.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Hymecromone plus Standard Of Care for six months

6 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

9 months

What Are the Treatments Tested in This Trial?

Interventions

• Hymecromone

Trial Overview The study tests the effectiveness of hymecromone added to standard care versus standard care alone in treating PSC. It will measure changes in liver enzymes (ALP), fibrosis via FibroScan, serum Hyaluronan levels indicating inflammation, and T-cell counts over a period of six months.

How Is the Trial Designed?

Group I: Hymecromone Experimental Treatment 1 Intervention

Participants will receive Hymecromone for six months + Standard Of Care (SOC), and will be followed for an additional nine months.

Group II: Standard Of Care (SOC) Active Control 1 Intervention

Participants will receive Standard Of Care (SOC), and will be followed for 15 months.

Hymecromone is already approved in European Union for the following indications:

Approved in European Union as Hymecromone for:

• Biliary spasm

Who Is Running the Clinical Trial?

Aparna Goel

Lead Sponsor

Trials

1

Recruited

20+

Paul Bollyky

Lead Sponsor

Trials

2

Recruited

40+

Published Research Related to This Trial

The study identified 24 metabolites of chamaechromone in rats, with 20 being novel, highlighting its complex metabolic pathways involving processes like hydroxylation and methylation.

Chamaechromone undergoes extensive Phase I and Phase II metabolism, which is crucial for understanding its safety and efficacy as a potential therapeutic agent, especially given its use in traditional medicine.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Metabolites characterization of chamaechromone in vivo and in vitro by using ultra-performance liquid chromatography/Xevo G2 quadrupole time-of-flight tandem mass spectrometry. Lou, Y., Zheng, J., Wang, B., et al.[2013]

Chamaechromone, found in the roots of Stellera chamaejasme, has been shown to have antihepatitis B virus activity, and its metabolism in the human liver involves specific enzymes that could influence its efficacy.

The study identified key metabolic pathways for chamaechromone, revealing that its hydroxylation is primarily catalyzed by cytochrome P450 1A2 and glucuronidation by several UDP-glucuronosyltransferases, which could affect how the compound is processed in the body.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Metabolism of chamaechromone in vitro with human liver microsomes and recombinant human drug-metabolizing enzymes. Lou, Y., Hu, H., Qiu, Y., et al.[2014]

Researchers isolated two new compounds from the roots of Prionosciadium thapsoides, identified as dihydrofurochromones, which could have potential therapeutic applications.

The structures of these new compounds were confirmed using advanced techniques like NMR and X-ray diffraction, ensuring their chemical configurations are accurately understood.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dihydrofurochromones from Prionosciadium thapsoides. Torres-Valencia, JM., Chávez-Ríos, OE., Cerda-García-Rojas, CM., et al.[2011]

A new compound called sophorophenolone was discovered from the pericarps of Sophorajaponica L., along with 13 other known compounds, indicating the potential for further research into their medicinal properties.

The structure of sophorophenolone was thoroughly characterized using advanced techniques like UV, IR, MS, and various NMR spectroscopy methods, which helps in understanding its chemical properties and potential applications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A new coumaronochromone from Sophora japonica. Tang, YP., Hu, J., Wang, JH., et al.[2009]

A new compound, 3,3-dimethylallylspatheliachromene methyl ether, was isolated from the plant Dictyoloma vandellianum and showed significant cytotoxic activity against tumor cell lines, with IC50 values between 6.26 and 14.82 μg/ml.

This compound also exhibited a moderate level of cytotoxicity in non-tumor cells (PBMC), with an IC50 value of 11.65 μg/ml, indicating a potential therapeutic window for further investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pyranochromones from Dictyoloma vandellianum A. Juss and Their Cytotoxic Evaluation. Alves, IM., Abreu, LS., Costa, CO., et al.[2017]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05295680

Study Details | NCT05295680 | Oral Hymecromone to Treat ... Primary objective: To evaluate the efficacy of hymecromone plus standard of care compared with standard of care alone in the treatment of adolescents and adults ...

2. withpower.com withpower.com/trial/phase-2-cholangitis-4-2022-3232b

Oral Hymecromone for Primary Sclerosing Cholangitis Hymecromone is unique because it is an oral drug that may offer a novel approach to treating Primary Sclerosing Cholangitis, a condition with limited treatment ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9202752/

Review of pharmacotherapeutic treatments for primary ... Hymecromone (4-methylumbelliferone) has been shown to reduce hyaluronan (HA) synthesis, which is elevated in diseases of chronic inflammation (99). A single- ...

4. peearz.com peearz.com/trialsindex?nctid=NCT05295680

Oral Hymecromone to Treat Adolescents and Adults With ... Primary objective: To evaluate the efficacy of hymecromone plus standard of care compared with standard of care alone in the treatment of adolescents and ...

5. clinicaltrials.stanford.edu clinicaltrials.stanford.edu/trials/o/NCT05295680.html

Oral Hymecromone to Treat Adolescents and Adults With ... To evaluate the efficacy of hymecromone plus standard of care compared with standard of care alone in the treatment of adolescents and adults with primary ...

6. clinconnect.io clinconnect.io/trials/NCT05295680

Oral Hymecromone to Treat Adolescents and Adults With This clinical trial is studying a medication called hymecromone to see if it can help treat adolescents and adults with a liver condition known as primary ...

7. aging.networkofcare.org aging.networkofcare.org/sanmateo/CommunityResources/ClinicalTrials/Detail/NCT05295680?keyword=%22Cholangitis%22

Oral Hymecromone to Treat Adolescents and Adults ... Primary objective: To evaluate the efficacy of hymecromone plus standard of care compared with standard of care alone in the treatment of adolescents and ...