Rosuvastatin and Gut Microbiome in Healthy Subjects

(INGEST Trial)

Recruiting at 1 trial location

Overseen By Sony Tuteja, PharmD, MS

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: Sony Tuteja

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 5 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 4

Duration: 8 weeks

62 Participants Needed

Trial Summary

What is the purpose of this trial?

There is evidence that the bacteria that naturally reside in the gut can influence how well we respond to medications. Therefore this study will look at how rosuvastatin, a medication used to lower cholesterol levels, may change the bacteria in the gut. Investigators will also examine how the gut bacteria will affect the ability of rosuvastatin to lower cholesterol levels. There will be 4 study visits over the course of about 16 weeks.The expected duration of the study is 2 years. Investigators plan to enroll 100 healthy volunteers during that time.

Will I have to stop taking my current medications?

Yes, you will need to stop taking any chronic medications, including over-the-counter medications and herbal supplements, except for oral contraceptives, to participate in this trial.

What data supports the effectiveness of the drug Rosuvastatin on the gut microbiome?

Research shows that Rosuvastatin can alter the gut microbiome by reducing the genetic potential to produce certain harmful compounds, which may be linked to its cholesterol-lowering effects. Additionally, changes in gut bacteria diversity and composition have been associated with better responses to statins, suggesting that Rosuvastatin's impact on the gut microbiome could play a role in its effectiveness. ^{1 2 3 4 5}

Is rosuvastatin safe for humans?

Rosuvastatin, also known as Crestor, is generally considered safe for humans, but it can alter the gut microbiome, which is the community of bacteria in the digestive system. While no harmful effects were noted in the studies, changes in gut bacteria could potentially influence how the body responds to the drug. ^{1 2 3 4 5}

How does the drug rosuvastatin differ from other treatments in affecting the gut microbiome?

Rosuvastatin is unique because it not only lowers cholesterol but also alters the gut microbiome by reducing the genetic potential to produce certain harmful metabolites, which may influence its effectiveness and side effects. ^{1 2 3 5 6}

Research Team

Sony Tuteja, PharmD, MS

Principal Investigator

University of Pennsylvania

Eligibility Criteria

Healthy volunteers aged 18 to 65, without diabetes, hypothyroidism, cancer history, gut inflammation disorders like IBD or celiac disease. Must not have used antibiotics in the last 6 months or be current smokers. Participants should not have cardiovascular diseases, kidney/liver dysfunction, extreme BMI values (<18.5 or >30), bowel resection surgery (except appendectomy), abnormal bowel frequency, and must agree to use birth control.

Inclusion Criteria

I am between 18 and 65 years old.

I understand the study and can agree to participate.

Exclusion Criteria

My liver enzyme levels are higher than normal.

I have diabetes with a fasting glucose level over 125mg/dL.

I have a history of inflammatory bowel diseases like IBD or celiac disease.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants are randomized to receive rosuvastatin 20 mg daily or placebo for eight weeks

8 weeks

3 visits (in-person)

Follow-up

Participants are monitored for changes in gut microbiome, fecal bile acids, and FGF19 levels

4 weeks

1 visit (in-person)

Treatment Details

Interventions

• Placebo
• Rosuvastatin

Trial Overview The study is testing how rosuvastatin affects gut bacteria and cholesterol levels in healthy individuals over approximately 16 weeks with four visits. It will also explore how gut bacteria influence the drug's effectiveness at lowering cholesterol.

Participant Groups

Group I: Rosuvastatin Experimental Treatment 1 Intervention

rosuvastatin 20 mg daily for eight weeks

Group II: Placebo Placebo Group 1 Intervention

placebo daily for eight weeks

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

Approved in United States as Crestor for:

• High cholesterol
• Hyperlipoproteinemia
• Prevention of cardiovascular disease

Approved in European Union as Crestor for:

• Hypercholesterolemia
• Mixed dyslipidemia
• Homozygous familial hypercholesterolemia

Approved in Canada as Crestor for:

• Hypercholesterolemia
• Mixed dyslipidemia
• Prevention of cardiovascular disease

Approved in Japan as Crestor for:

• Hypercholesterolemia
• Familial hypercholesterolemia

Who Is Running the Clinical Trial?

Sony Tuteja

Lead Sponsor

Trials

2

Recruited

70+

References

1. England pubmed.ncbi.nlm.nih.gov

Rosuvastatin alters the genetic composition of the human gut microbiome. [2021]

2. Korea (South) pubmed.ncbi.nlm.nih.gov

Comparative analysis of the gut microbiota in distinct statin response patients in East China. [2019]

3. Switzerland pubmed.ncbi.nlm.nih.gov

Gut Microbiome Associates With Lipid-Lowering Effect of Rosuvastatin in Vivo. [2020]

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

Alterations in Gut Microbiota by Statin Therapy and Possible Intermediate Effects on Hyperglycemia and Hyperlipidemia. [2020]

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

Atorvastatin Treatment Modulates the Gut Microbiota of the Hypercholesterolemic Patients. [2019]

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

The influence of rosuvastatin on the gastrointestinal microbiota and host gene expression profiles. [2017]