Simvastatin for Chronic Pancreatitis

(SMV in CP Trial)

Recruiting at 3 trial locations

Overseen By Arax Shanlian

Age: 18+

Sex: Any

Trial Phase: Phase < 1

Sponsor: Cedars-Sinai Medical Center

Must not be taking: Antifungals, Antibiotics, HIV drugs, others

Disqualifiers: Pregnancy, Pancreatic tumors, Transplant, others

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 15

Duration: 6 months

90 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether simvastatin, a drug typically used to lower cholesterol, can help individuals with Recurrent Acute Pancreatitis (RAP) or Chronic Pancreatitis (CP). Participants will receive either simvastatin or a placebo (a pill with no active medicine) once daily for six months. The trial seeks adults diagnosed with RAP or CP who do not have pancreatitis caused by gallstones, medications, trauma, or autoimmune issues. Individuals with frequent or ongoing pancreatitis and no prior pancreatic surgery may be suitable candidates for this study. As an Early Phase 1 trial, this research focuses on understanding how simvastatin affects people with pancreatitis, offering a unique opportunity to contribute to groundbreaking medical research.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop all current medications, but you cannot participate if you are taking certain drugs like itraconazole, ketoconazole, or simvastatin within the past 6 months. It's best to discuss your specific medications with the study team.

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

Research has shown that simvastatin is generally a safe and well-known drug for lowering cholesterol, and many people tolerate it well. However, some patients taking simvastatin have developed acute pancreatitis, a sudden inflammation of the pancreas. One study found no strong genetic link between simvastatin and pancreatitis, suggesting that regular monitoring might not be necessary.

While it's too early to draw final conclusions about simvastatin's safety for treating chronic pancreatitis, its common use for other conditions indicates it is usually safe. Always consult a doctor to discuss the risks and benefits before joining a trial. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for chronic pancreatitis, which often involve pain management and enzyme replacement therapy, simvastatin acts on inflammation and fibrosis by targeting cholesterol synthesis pathways. Researchers are excited about simvastatin because it may offer a new way to reduce the progression of pancreatic damage by addressing underlying inflammation rather than just managing symptoms. This approach could potentially improve long-term outcomes for patients, offering a novel therapeutic angle that current options do not address.

What evidence suggests that simvastatin might be an effective treatment for chronic pancreatitis?

Research has shown that simvastatin, which participants in this trial may receive, may help reduce swelling in the pancreas for people with pancreatitis. One study found that simvastatin lowered the risk of new sudden attacks of pancreatitis. Other research suggests that simvastatin might help with long-term pain and improve overall health in patients with ongoing or repeated pancreatitis. These promising findings indicate that simvastatin could potentially offer relief for those dealing with these painful conditions. ^{2 3 4 6 7}

Who Is on the Research Team?

Stephen Pandol, MD

Principal Investigator

Cedars-Sinai Medical Center

Are You a Good Fit for This Trial?

Adults aged 18-75 with Recurrent Acute Pancreatitis or Chronic Pancreatitis not caused by gallstones, medications, trauma, or autoimmune issues. Participants must be able to take oral meds and commit to the study's duration. Women of childbearing age and men must use effective contraception.

Inclusion Criteria

Provision of signed and dated informed consent form

For females of reproductive potential: use of highly effective contraception for at least 1 month prior to screening and agreement to use such a method during study participation and for an additional one month after administration of study medication

Stated willingness to comply with all study procedures and availability for the duration of the study

Exclusion Criteria

History of solid organ transplant, HIV/AIDS

Pregnancy or lactation

Known Pregnancy

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Simvastatin or placebo for 6 months to assess its impact on pain and quality of life in chronic pancreatitis

6 months

Visits at baseline, 3 months, and 6 months

Follow-up

Participants are monitored for safety and effectiveness after treatment, with outcome measures collected 6 months post-treatment

6 months

Final visit at 12 months

What Are the Treatments Tested in This Trial?

Interventions

• Placebo
• Simvastatin

Trial Overview The trial is testing simvastatin's effectiveness for improving patient-reported outcomes in those with Recurrent Acute Pancreatitis (RAP) and Chronic Pancreatitis (CP). It compares simvastatin against a placebo to see if it can help manage pancreatitis symptoms.

How Is the Trial Designed?

Group I: Simvastatin Experimental Treatment 1 Intervention

Participants receive Simvastatin 40mg capsule once daily for 6 months.

Group II: Placebo Placebo Group 1 Intervention

Participants receive Placebo capsule matching Simvastatin once daily for 6 months.

Simvastatin is already approved in European Union, United States, Canada, Japan for the following indications:

Approved in European Union as Zocor for:

• Hypercholesterolemia
• Cardiovascular disease

Approved in United States as Zocor for:

• Hypercholesterolemia
• Cardiovascular disease

Approved in Canada as Zocor for:

• Hypercholesterolemia
• Cardiovascular disease

Approved in Japan as Zocor for:

• Hypercholesterolemia
• Cardiovascular disease

Who Is Running the Clinical Trial?

Cedars-Sinai Medical Center

Lead Sponsor

Trials

523

Recruited

165,000+

United States Department of Defense

Collaborator

Trials

940

Recruited

339,000+

Published Research Related to This Trial

A review of 311 individual case safety reports (ICSRs) from the WHO database revealed that musculoskeletal disorders were the most common adverse drug reactions (ADRs) in children and adolescents taking statins, accounting for 27.3% of reported cases.

The study highlighted serious safety concerns, including 42.8% of reports being classified as 'serious' with 11 deaths primarily due to intentional overdoses in adolescents, indicating a need for increased monitoring and reporting of statin ADRs in pediatric populations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adverse drug reactions of statins in children and adolescents: a descriptive analysis from VigiBase, the WHO global database of individual case safety reports. Conte, C., Rousseau, V., Vert, C., et al.[2021]

In a study involving 2845 patients and 8954 treatment cycles, ustekinumab and secukinumab were found to have the lowest rates of adverse events compared to other systemic drugs for psoriasis, indicating a safer profile for these treatments.

Conversely, cyclosporine and infliximab were associated with the highest rates of adverse events, suggesting that these medications may carry more risks for patients with moderate to severe psoriasis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term safety of nine systemic medications for psoriasis: A cohort study using the Spanish Registry of Adverse Events for Biological Therapy in Dermatological Diseases (BIOBADADERM) Registry. Daudén, E., Carretero, G., Rivera, R., et al.[2021]

Brodalumab, an IL-17 antagonist approved for moderate-to-severe plaque psoriasis, has a safety profile similar to other IL-17 treatments, based on data from phase II and III clinical trials.

While common adverse events include nasopharyngitis and upper respiratory infections, a significant concern arose from six reported suicides among patients, leading to a black box warning, although no direct causal link was established.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Brodalumab: A Review of Safety. Rusta-Sallehy, S., Gooderham, M., Papp, K.[2019]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT02743364

Simvastatin in Reducing Pancreatitis in Patients With ... This randomized phase II trial studies how well simvastatin works in reducing pancreatitis (the inflammation of the pancreas) in patients with pancreatitis ...

2. clinicaltrials.cedars-sinai.edu clinicaltrials.cedars-sinai.edu/view/STUDY00002293

Simvastatin Treatment to Improve Patient-Reported Outcomes ... Researchers hope that simvastatin will have positive effects in reducing chronic pain associated with chronic pancreatitis and recurrent acute pancreatitis, in ...

3. trialx.com trialx.com/clinical-trials/listings/297233/simvastatin-treatment-to-improve-patient-reported-outcomes-in-patients-with-chronic-pancreatitis/

Simvastatin Treatment to Improve Patient-reported ... The Study Team hypothesizes that treatment with simvastatin will have a significant benefit for reducing pain, improving health-related quality ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8887796/

A Randomized, Double-Blinded, Placebo-Controlled Trial ... A pooled analysis of 16 randomized-controlled trials of statin with other disease endpoints reported a reduced risk of acute pancreatitis (risk ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7902790/

Simvastatin in the Prevention of Recurrent Pancreatitis We hypothesized that simvastatin, a widely used patent-free statin, reduces the number of new episodes of AP or inflammatory relapses in CP in ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10839132/

Statin Therapy and Pancreatitis: A Multi-Institutional ... Results: Patients on statin therapy were significantly more likely to develop acute pancreatitis compared to patients not taking statin therapy ...

7. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1424390325001206

A Mendelian Randomization Study Investigating the ... Genetic evidence has not proven a causality between simvastatin and pancreatitis, suggesting that routine monitoring may be unnecessary.