Clinical trial NCT03327051
Conditions: Probiotics
Sponsor: Stanford University
Start date: 2018-03-20; Completion date: 2018-12-30
Enrollment: 39 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
Probiotics are over-the-counter dietary products with microorganisms that are generally consumed for health benefit. However, the durability of these microorganisms is unclear, particularly when they pass through the highly acidic environment of the stomach. We will test the colonization of these microorganisms among individuals who consume probiotics with and without acid suppression therapy.

Detailed description:
All activities will be related to research. Participants will be randomized to receive either over-the-counter acid suppression medication or placebo from weeks -2 through week 4. All participants will receive VSL #3 (over-the-counter probiotic) from weeks 0 through 4. Survey data, serum, and stool samples will be collected at weeks -2, 0, and 4.

The intervention medication and probiotics have a very low side effect profile and are available over the counter. All data collection methods are non-invasive.

Elucidation of the effects of acid suppression on probiotic colonization will allow us to better understand the utility of probiotics use by individuals on acid suppression medications.

Arms: arm 1: Participants will receive a proton pump inhibitor (Omeprazole) and VSL #3 Probiotics arm 2: Participants will receive placebo and VSL #3 Probiotics
Interventions: intervention 1: Omeprazole intervention 2: VSL #3 intervention 3: Placebo
Intervention descriptions: intervention 1: Proton pump inhibitor (PPI) that suppresses gastric acid secretion intervention 2: Probiotics intervention 3: Placebo to match omeprazole

Protocol documents:
Prot_000.pdf: 
 
 
The Effect of Gastric Acid Suppression on Probiotic Colonization 
Study Protocol 
NCT03327051 
 August 28, 2018 


The Effect of Gastric Acid Suppression on Probiotic Colonization 
 
BACKGROUND 
 
A major role of gastric acidity is the digestion of food products and the elimination of potentially 
pathogenic bacteria that enter the gastrointestinal tract. The use of pharmacologic agents that 
reduce gastric acid secretion (i.e., H2 receptor antagonists and proton pump inhibitors) has 
consequently been shown to influence the composition of the intestinal microflora.1-3 Probiotics 
contain living microorganisms that are consumed for its putative benefits on the intestinal 
microbiota and intestinal health. However, despite widespread use of probiotics and acid 
suppressing effects, the effect of gastric acid suppression on the survival and colonization of 
probiotics organisms is currently unclear. We hypothesize that pharmacology-mediated gastric 
acid suppression will increase the colonization potential of probiotics. We propose to test this 
hypothesis in a randomized double-blinded placebo-controlled trial among healthy controls who 
initiate probiotics. 
 
METHODS 
 
• 
Study design: Randomized double-blind placebo-controlled trial 
• 
Population: 15 + 15 healthy controls 
• 
Exclusion criteria: any gastrointestinal condition, soy or gluten sensitivity, allergy to proton 
pump inhibitors, any chronic medical condition other than hypertension or hyperlipidemia, 
pregnancy, consuming herbs or probiotics 
• 
Interventions 
o PPI (omeprazole 20 mg/day) + VSL #3 (900 billion bacteria) 
o VSL #3 (900 billion bacteria) 
• 
Primary outcome 
o Quantitation of bacterial strains found in VSL #3 (S. thermophiles, B. breve, B. 
longum, B. infantis, L. acidophilus, L. plantarum, L. paracasei, L. delbrueckii subsp. 
bulgaricus) 
• 
Secondary outcomes 
o Characterization of microbiota 
o Metabolome 
o Safety (reported symptoms) 
 
Study Visits 
• 
Timeline 
o Week -2: Run-in with either PPI or nothing x 2 weeks 
o Week 0: Initiation of VSL #3 x 4 weeks 
o Diet/symptom survey, blood, and stool collection at weeks -2, 0, and 4 
 
 


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Data Storage 
Paper records will be stored in a secure, locked cabinet at the Stanford Center for Clinical 
Research. Electronic clinical data will be stored on a REDCap database hosted on Stanford IT-
managed servers. 
 
REFERENCES 
 
1. 
Freedberg DE, Toussaint NC, Chen SP, et al. Proton Pump Inhibitors Alter Specific Taxa 
in the Human Gastrointestinal Microbiome: A Crossover Trial. Gastroenterology. 
2015;149(4):883-885 e889. 
2. 
Imhann F, Bonder MJ, Vich Vila A, et al. Proton pump inhibitors affect the gut 
microbiome. Gut. 2016;65(5):740-748. 
3. 
Jackson MA, Goodrich JK, Maxan ME, et al. Proton pump inhibitors alter the 
composition of the gut microbiota. Gut. 2016;65(5):749-756. 
 
 

SAP_001.pdf: 
 
 
The Effect of Gastric Acid Suppression on Probiotic Colonization 
Statistical Analysis Plan 
NCT03327051 
 December 13, 2019 
 
The relative percentage abundance was obtained by summing the levels of VSL#3 
probiotic strains detected in the study samples. Statistical analysis was performed using 
GraphPad prizm. Two-way ANOVA with Bonferroni posttest was used for multi-variable 
analyses (within-group differences between week 0 and week 4). A p-value of <0.05 
would be considered statistically significant.