Rosuvastatin and Gut Microbiome in Healthy Subjects

(INGEST Trial)

Not currently recruiting at 1 trial location

Overseen By Sony Tuteja, PharmD, MS

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: Sony Tuteja

Must not be taking: Antihypertensives, Antibiotics, Probiotics, others

Disqualifiers: Cardiovascular disease, Cancer, Diabetes, others

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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to explore how rosuvastatin, a cholesterol-lowering medication, affects gut bacteria in healthy individuals and how these bacteria might influence the medication's effectiveness. Researchers will divide participants into two groups: one receiving rosuvastatin and the other a placebo (a harmless pill with no active drug), each for eight weeks. Ideal candidates are healthy individuals without a history of heart disease, diabetes, or certain other medical conditions, and who are non-smokers. As a Phase 4 trial, this research focuses on understanding how this FDA-approved and effective treatment can benefit more patients.

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 is the safety track record for these treatments?

Research has shown that rosuvastatin is generally safe and effectively lowers cholesterol while being well-tolerated. The FDA has approved rosuvastatin for this purpose, indicating it has passed several safety checks.

Studies on rosuvastatin and the gut have not reported any major safety concerns. While it might slightly alter gut bacteria, no harmful effects have been found. Thus, taking rosuvastatin is unlikely to cause significant gut health issues.

In summary, rosuvastatin is considered safe for managing cholesterol. Current research does not reveal any new safety problems related to its effect on gut bacteria. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Rosuvastatin is unique because it not only lowers cholesterol but also has the potential to influence the gut microbiome, which is a new frontier in health research. Unlike other treatments for cholesterol that focus solely on reducing LDL levels, rosuvastatin may offer additional health benefits by interacting with the gut flora. Researchers are excited about this treatment because it could lead to a broader understanding of how cholesterol medications impact overall health beyond just managing cholesterol levels.

What evidence suggests that rosuvastatin might be an effective treatment for lowering cholesterol levels?

In this trial, participants will receive either rosuvastatin or a placebo. Research has shown that rosuvastatin, a drug commonly used to lower cholesterol, can also alter gut bacteria. One study found that people taking rosuvastatin had more diverse gut bacteria. This change in gut bacteria is linked to the drug's effectiveness in lowering cholesterol. Additionally, individual differences in gut bacteria can affect responses to rosuvastatin. Overall, rosuvastatin effectively lowers cholesterol, and gut bacteria might assist in this process. ^{1 2 3 4 6}

Who Is on the Research Team?

Sony Tuteja, PharmD, MS

Principal Investigator

University of Pennsylvania

Are You a Good Fit for This Trial?

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 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 for a Trial Participant

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)

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Citations

1. nature.com nature.com/articles/s41598-020-62261-y

Rosuvastatin alters the genetic composition of the human ... Participants on rosuvastatin treatment showed an increase in gut microbial richness (delta Chao1, paired t-test p = 0.04), but this increase was ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5874287/

Gut Microbiome Associates With Lipid-Lowering Effect ... These data showed the distribution profiles of gut microbiome in rosuvastatin-treated patients with different age and clinical outcomes (Table 3) ...

3. lipidworld.biomedcentral.com lipidworld.biomedcentral.com/articles/10.1186/s12944-018-0801-x

The influence of the intestinal microflora to the efficacy of ... 16S rDNA sequencing results in our study showed that Rosuvastatin treatment for 2 weeks, significantly reduced Lactobacillus and Bifidobacterium ...

4. ahajournals.org ahajournals.org/doi/10.1161/CIRCGEN.119.002314

Gut Microbiome and Response to Cardiovascular Drugs A proof-of-concept study in human subjects with hyperlipidemia showed that 4 to 8 weeks of rosuvastatin treatment significantly altered the gut ...

5. sciencedirect.com sciencedirect.com/science/article/pii/S2666634022001738

Heterogeneity in statin responses explained by variation in ... We find that heterogeneity in statin responses was consistently associated with variation in the gut microbiome across two independent cohorts.

6. journals.physiology.org journals.physiology.org/doi/abs/10.1152/ajpgi.00149.2016

The influence of rosuvastatin on the gastrointestinal ... This work demonstrates that rosuvastatin administration in mice affects the gastrointestinal microbiota, influences bile acid metabolism, and alters ...