Proton Pump Inhibitors for Gut Health in Healthy Subjects

Overseen By Jennifer Taufui

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Envivo Bio Inc

Must not be taking: Daily PPIs

Disqualifiers: Gastric surgery, Bowel obstruction, IBD, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

Duration: 8 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how proton pump inhibitors (medications that reduce stomach acid) affect the gut's natural bacteria and metabolism in healthy individuals. The goal is to understand any changes in gut health when these inhibitors are used. The study seeks participants who are generally healthy, have not undergone major stomach or esophagus surgeries, and are not currently using proton pump inhibitors daily. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants a chance to contribute to foundational scientific knowledge.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot have used proton pump inhibitors daily in the last 30 days.

Is there any evidence suggesting that proton pump inhibitors are likely to be safe for humans?

Research has shown that proton pump inhibitors (PPIs) are generally safe for short-term use. A large study found that these drugs did not lead to serious health issues like pneumonia, chronic kidney disease, or diabetes. Another study identified mild side effects, such as headaches, nausea, or an upset stomach.

However, long-term use of PPIs might increase the risk of certain infections. For example, there is a link to a higher chance of infections like Clostridium difficile, which can cause stomach problems. Overall, while many people tolerate PPIs well, it's important to weigh the benefits and risks, especially with long-term use. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Proton pump inhibitors (PPIs) are unique because they work by blocking the enzyme system responsible for secreting gastric acid in the stomach. Unlike antacids that neutralize existing stomach acid or H2 blockers that reduce acid production, PPIs target and inhibit the proton pumps more directly and effectively. Researchers are excited about PPIs because they offer longer-lasting relief from acid-related issues and have the potential to maintain gut health in healthy individuals by managing acid levels more precisely.

What evidence suggests that proton pump inhibitors might be effective for gut health?

Studies have shown that proton pump inhibitors (PPIs) effectively reduce stomach acid, aiding in the treatment of acid-related issues. However, they also impact the gut microbiome, the community of bacteria, viruses, and fungi in the digestive system. Research indicates that PPIs can alter the balance of these microorganisms, potentially leading to digestive problems like bacterial overgrowth. Observational studies have linked long-term PPI use to risks such as infections and nutrient deficiencies. While PPIs are powerful for their primary purpose, changes in gut health remain an important consideration. ^{6 7 8 9 10}

Are You a Good Fit for This Trial?

This trial is for healthy adults aged 18-85 who can understand English and the study's requirements. Women must have a negative pregnancy test and agree to use effective contraception. People with gastric issues, substance abuse, unstable health conditions, or recent proton pump inhibitor use cannot participate.

Inclusion Criteria

ASA Classification 1 or 2

For women of childbearing potential, negative urine pregnancy test within 7 days of Screening Visit. Willingness to use highly effective contraception during the entire study period (e.g.: implants, injectables, oral contraceptives, intra-uterine device or declared abstinence)

Subject is fluent in English and understands the study protocol and informed consent and is willing and able to comply with study requirements and sign the informed consent form.

Exclusion Criteria

I have had a blockage in the stomach that prevents food from leaving.

I have a history of delayed stomach emptying.

Pregnancy or planned pregnancy within 30 days from Screening Visit, or breast-feeding

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive proton pump inhibitors and samples are collected using the CapScan capsule to evaluate gut microbiota and metabolites

8 weeks

Regular visits for sample collection

Follow-up

Participants are monitored for changes in gut microbiota and metabolites after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Proton Pump Inhibitors

Trial Overview The study tests how proton pump inhibitors affect gut microbiota composition and metabolic profiles in healthy volunteers using CapScan collection capsules.

Who Is Running the Clinical Trial?

Envivo Bio Inc

Lead Sponsor

Trials

2

Recruited

40+

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4254461/

The impact of proton pump inhibitors on the human ... PPIs are highly effective treatment for acid-related disorders but are widely overused. PPIs alter the microbiome throughout the human gastrointestinal tract ...

2. frontiersin.org frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2023.1217306/full

Proton pump inhibitors may enhance the risk of digestive ... Although PPIs exhibit exceptional acid inhibition effects, various studies have linked PPI use with adverse digestive events, such as small intestinal bacterial ...

3. consultqd.clevelandclinic.org consultqd.clevelandclinic.org/long-term-use-of-ppis-has-consequences-for-gut-microbiome

Long-term Use of PPIs Has Consequences for Gut Microbiome “PPIs also actually impact the function of the gut bacteria, and target the bacterial, viral and fungal proton pumps in the gut microbiome,” she ...

4. gutnliver.org gutnliver.org/journal/view.html?doi=10.5009/gnl15502

25 Years of Proton Pump Inhibitors: A Comprehensive ... Pooled data from 384 randomized controlled trials (RCTs) which included a total of 44,870 patients concluded that omeprazole was significantly more effective (p ...

5. mdpi.com mdpi.com/1648-9144/61/9/1569

Proton Pump Inhibitors (PPIs)—An Evidence-Based ... Observational studies link chronic PPI use to a myriad of adverse outcomes such as enteric infections (e.g., Clostridioides difficile), nutrient deficiencies ( ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10248387/

Adverse Effects Associated with Long-Term Use of Proton ... Long-term PPI use has been linked to an increase in the incidence of infections such as Clostridium difficile infection, community-acquired pneumonia (CAP), and ...

7. nature.com nature.com/articles/s41598-019-39335-7

Analysis of postmarketing safety data for proton-pump ... The most common PPI adverse reactions (ADRs) are mild and include headache, nausea, stomach pain, diarrhea, vomiting, and flatulence. Serious ...

8. gastrojournal.org gastrojournal.org/article/S0016-5085%2819%2940974-8/fulltext

Safety of Proton Pump Inhibitors Based on a Large, Multi ... In conclusion, these data suggest PPI therapy is safe for up to a median of 3 years. As with all drugs, PPI therapy should only be used when the benefits are ...

9. gut.bmj.com gut.bmj.com/content/65/5/740

Proton pump inhibitors affect the gut microbiome - The BMJ Proton pump inhibitors (PPI) use is associated with increased risk of enteric infections, in particular with a 65% increase in incidence of Clostridium ...

10. gastro.org gastro.org/press-releases/large-placebo-controlled-trial-confirms-safety-of-proton-pump-inhibitors-ppis/

Large placebo-controlled trial confirms safety of proton ... Researchers find no evidence to support claims that PPIs cause serious health issues such as pneumonia, chronic kidney disease, diabetes and dementia.