Atorvastatin for Ulcerative Colitis

Recruiting in Palo Alto (17 mi)

+4 other locations

Overseen by Seema A. Khan, M.D.

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

Sponsor: Northwestern University

Must be taking: Mesalamine, Thiopurines, Biologics

Must not be taking: Corticosteroids, Statins, Cyclosporine, others

Disqualifiers: Ulcerative proctitis, HIV, Pregnancy, others

Prior Safety Data

Approved in 6 Jurisdictions

Trial Summary

What is the purpose of this trial?

This trial studies atorvastatin, a cholesterol-lowering drug, in patients with ulcerative colitis who are at risk of colon cancer. The goal is to see if atorvastatin can reduce cancer risk by lowering cholesterol and affecting certain proteins and genes linked to cancer.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop all current medications, but you must not have used statins in the last 12 months or corticosteroids in the past 3 months. You also cannot use certain medications like cyclosporine, fibrates, or strong CYP3A4 inhibitors or inducers.

What data supports the effectiveness of the drug atorvastatin for treating ulcerative colitis?

Research shows that atorvastatin, when combined with another drug called mesalazine, can reduce inflammation and symptoms in a rat model of ulcerative colitis. This combination therapy was more effective than using either drug alone, suggesting atorvastatin may help manage ulcerative colitis by reducing inflammation.

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Is atorvastatin generally safe for humans?

Atorvastatin is generally considered safe for humans, but there is a case report of severe stomach ulcers in a person taking atorvastatin, which resolved after stopping the drug. This suggests that while rare, serious side effects can occur, and any new abdominal pain should be reported to a doctor.

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How does atorvastatin differ from other drugs for ulcerative colitis?

Atorvastatin is unique for ulcerative colitis because it has anti-inflammatory effects that are not directly related to its cholesterol-lowering activity, and it can enhance anti-inflammatory effects when combined with mesalazine, potentially improving outcomes by targeting specific inflammatory pathways.

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Eligibility Criteria

Adults aged 18-70 with longstanding ulcerative colitis and a specific P53 mutation, in clinical remission for at least 8 years. They must not have used statins or had chemotherapy within the last year or two respectively, no recent corticosteroid use, and cannot be pregnant. Participants should have stable cholesterol levels and agree to contraception during the study.

Inclusion Criteria

Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (SGPT) =< 1.5 X institutional upper limit of normal (ULN)

I am between 18 and 70 years old.

I have had ulcerative colitis for over 8 years and am in remission, confirmed by yearly endoscopy.

Exclusion Criteria

Pregnant or lactating participants are excluded

I have used corticosteroids in the last 3 months due to a high risk of my disease returning.

I have not had chemotherapy in the last 2 years.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive atorvastatin or placebo orally once daily for 12 months, with colonoscopy and blood collection

12 months

Monthly visits for monitoring and sample collection

Follow-up

Participants are monitored for safety and effectiveness after treatment completion

2 weeks

1 visit (in-person)

Participant Groups

The trial is testing if Atorvastatin can lower colon cancer risk in patients with ulcerative colitis who are at increased risk of large intestinal cancer. It involves taking Atorvastatin versus a placebo while monitoring health through biopsies, blood tests, questionnaires, and biospecimen collection.

Group I: Arm I (atorvastatin, biospecimen collection) Experimental Treatment 4 Interventions

Patients receive atorvastatin PO QD for 12 months. Patients also undergo colonoscopy with biopsy, and collection of blood on the trial.

Group II: Arm II (placebo, biospecimen collection) Placebo Group 4 Interventions

Patients receive placebo PO QD for 12 months. Patients also undergo colonoscopy with biopsy, and collection of blood on the trial.

Atorvastatin Calcium is already approved in European Union, United States, Canada, Japan, China, Switzerland for the following indications:

🇪🇺 Approved in European Union as Lipitor for:

• Hypercholesterolemia
• Mixed dyslipidemia
• Prevention of cardiovascular disease

🇺🇸 Approved in United States as Lipitor for:

• Hypercholesterolemia
• Mixed dyslipidemia
• Prevention of cardiovascular disease
• Reduction of risk of myocardial infarction, stroke, angina, and revascularization procedures

🇨🇦 Approved in Canada as Lipitor for:

• Hypercholesterolemia
• Mixed dyslipidemia
• Prevention of cardiovascular disease

🇯🇵 Approved in Japan as Lipitor for:

• Hypercholesterolemia
• Mixed dyslipidemia
• Prevention of cardiovascular disease

🇨🇳 Approved in China as Lipitor for:

• Hypercholesterolemia
• Mixed dyslipidemia
• Prevention of cardiovascular disease

🇨🇭 Approved in Switzerland as Lipitor for:

• Hypercholesterolemia
• Mixed dyslipidemia
• Prevention of cardiovascular disease

Find a Clinic Near You

Research Locations Nearby Select from list below to view details:

National Cancer Institute Rockville, MD

Loma Linda University Medical Center Loma Linda, CA

University of Kansas Cancer Center Kansas City, KS

Northwestern University Chicago, IL

More Trial Locations

Who Is Running the Clinical Trial?

Northwestern University Lead Sponsor

National Cancer Institute (NCI) Collaborator

References

1. Switzerland pubmed.ncbi.nlm.nih.gov

Disease modifying effect of statins in dextran sulfate sodium model of mouse colitis. [2018] We evaluated the disease modifying effect of simvastatin and atorvastatin in Dextran Sulfate Sodium (DSS) model of colitis.

2. England pubmed.ncbi.nlm.nih.gov

Lipid Profiles in Patients With Ulcerative Colitis Receiving Tofacitinib-Implications for Cardiovascular Risk and Patient Management. [2022] Patients with ulcerative colitis (UC) are at elevated risk of cardiovascular disease vs the general population, despite a lower prevalence of traditional risk factors, including hyperlipidemia. Mechanistic studies in patients with rheumatoid arthritis and psoriasis suggest that tofacitinib restores serum lipids to preinflammation levels by reversing inflammation-induced cholesterol metabolism changes. We reviewed data on lipid levels and cardiovascular events, alongside recommendations for managing lipid levels during tofacitinib treatment in patients with UC, based on up-to-date expert guidelines.

3. Poland pubmed.ncbi.nlm.nih.gov

[Treatment optimization of subclinical atherosclerosis in patients with ulcerative colitis]. [2015] In this article we assessed the positive impact of statins and omega-3 polyunsaturated fatty acids on achieving target lipid levels, acute phase proteins in patients with ulcerative colitis and subclinical atherosclerosis.

4. Switzerland pubmed.ncbi.nlm.nih.gov

Dyslipidaemia Is Associated with Severe Disease Activity and Poor Prognosis in Ulcerative Colitis: A Retrospective Cohort Study in China. [2023] Background: Clinical data on the correlation of dyslipidaemia with the long-term outcomes of ulcerative colitis (UC) are limited. This study aimed to evaluate the impact of lipid levels on disease activity and prognosis in UC. Methods: The retrospective data of UC patients who had detailed lipid profiles were collected from January 2003 to September 2020. All patients were followed-up to 30 September 2021. The long-term outcomes were UC-related surgery and tumorigenesis. Results: In total, 497 patients were included in the analysis. Compared to patients with normal lipid levels, those with dyslipidaemia commonly presented with more serious disease activity. Low high-density lipoprotein cholesterol (p

5. England pubmed.ncbi.nlm.nih.gov

Targeting IL-10, ZO-1 gene expression and IL-6/STAT-3 trans-signaling by a combination of atorvastatin and mesalazine to enhance anti-inflammatory effects and attenuates progression of oxazolone-induced colitis. [2021] Ulcerative colitis (UC) is a chronic inflammatory disease characterized by diffused inflammation of the colon and rectum mucosa. The pathogenesis of UC is multifactorial, and the exact underlying mechanisms remain poorly understood. This study aims to investigate the effect of mesalazine and atorvastatin combination in enhancing anti-inflammatory effects and attenuates progression of oxazolone colitis in rats. In the present study, male albino rats (N = 60) were divided into six groups (10 rats each), the first two groups served as normal control and a control saline group. Colitis was induced by intra-rectal administration of oxazolone in the 5th and 7th days after pre-sensitization. Then, rats were divided into untreated group, groups treated with mesalazine or atorvastatin or their combination. Colitis was assessed by colon length, body weight, and incidence of diarrhea, rectal bleeding, and histopathology of colon tissue. Colon tissues were used for measuring interleukin 6 (IL-6), tumor necrosis factor alpha (TNF-α), IL-13, signal transducer and activator of transcription-3 (STAT-3), myeloperoxidase activity (MPO), reduced glutathione(GSH), and tissue expression of IL-10, tight junction protein zonula occludens (ZO-1), and caspase-3 genes. The combination therapy significantly attenuated progression of UC by decreasing incidence of diarrhea, rectal bleeding, weight loss, IL-13, IL-6, TNF-α, STAT-3, caspase-3, and MPO activity and significantly increased IL-10, ZO-1, colon length, and GSH content, and these effects were more superior to single drugs. These findings showed that combination therapy was able to ameliorate progression of UC and enhance anti-inflammatory effects possibly by restoring IL-10 and ZO-1 levels and limiting IL-6/STAT-3 trans-signaling.

6. United States pubmed.ncbi.nlm.nih.gov

Atorvastatin-induced severe gastric ulceration: a case report. [2019] A 41-year-old man presented with severe gastric ulceration 3 mo after beginning treatment with atorvastatin 20 mg once daily for hypercholesterolemia. The patient was not taking any ulcerogenic drugs and had no evidence of Helicobacter pylori infection. Proton pump inhibitor therapy was initiated and atorvastatin was replaced by simvastatin with complete resolution of gastrointestinal symptoms. To our knowledge, this is the first report of atorvastatin-induced gastric ulceration, which should be looked for in patients who develop abdominal pain while on this drug.

7. India pubmed.ncbi.nlm.nih.gov

Randomized clinical trial: atorvastatin versus placebo in patients with acute exacerbation of mild to moderate ulcerative colitis. [2021] Statins are known to possess pleiotropic anti-inflammatory properties which have been evaluated for clinical benefits in a number of disorders. Studies have demonstrated beneficial actions of statins in experimental models of colitis. Clinical evidence in acute exacerbation of ulcerative colitis (UC) is lacking.

8. India pubmed.ncbi.nlm.nih.gov

Protective effect of simvastatin and rosuvastatin on trinitrobenzene sulfonic acid-induced colitis in rats. [2018] Statins have anti-inflammatory effects that are not directly related to their cholesterol lowering activity. This study was carried out to evaluate the effect of simvastatin or rosuvastatin on the extent of colonic mucosal damage and on the inflammatory response in trinitrobenzene sulfonic acid (TNBS)-induced ulcerative colitis.