PR: Gastric Acid Suppression and Probiotic Colonization

• Sponsor: Stanford University (Other)
• Overall Status: Completed
• CT.gov ID: NCT03327051
• Collaborator: (none)
• Enrollment: 39
• Location: 1
• Arms: 2
• Actual Duration (Months): 9.4
• Patients Per Site Per Month: 4.2

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Probiotics	Drug: Omeprazole; Dietary Supplement: VSL #3; Drug: Placebo	Phase 4

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 39 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Basic Science
• Official Title: The Effect of Gastric Acid Suppression on Probiotic Colonization
• Actual Study Start Date: Mar 20, 2018
• Actual Primary Completion Date: Dec 30, 2018
• Actual Study Completion Date: Dec 30, 2018

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Omeprazole and VSL #3 Participants will receive a proton pump inhibitor (Omeprazole) and VSL #3 Probiotics	Drug: Omeprazole; Proton pump inhibitor (PPI) that suppresses gastric acid secretion; Dietary Supplement: VSL #3; Probiotics
Placebo Comparator: Placebo and VSL #3 Participants will receive placebo and VSL #3 Probiotics	Dietary Supplement: VSL #3; Probiotics; Drug: Placebo; Placebo to match omeprazole

Outcome Measures

Primary Outcome Measures

1. Relative Abundance of VSL#3 Probiotic Bacterial Strains When Ingested in the Presence or Absence of the Proton Pump Inhibitor (PPI) Omeprazole at Week 4. [Week 4]

   Relative abundance is reported as the percent of combined VSL #3 probiotic bacteria strains in the bacteria sample (S. thermophiles, B. breve, B. longum, B. infantis, L. acidophilus, L. plantarum, L. paracasei, L. delbrueckii subsp. bulgaricus) following their ingestion in the presence or absence of the gastric acid suppression drug omeprazole. Stool samples were assessed.

Secondary Outcome Measures

1. Number of Participants With Symptoms Related to VSL#3 Treatment. [Week 0 through Week 4]

   Participants were asked to report symptoms of gastro-intestinal discomfort experienced within the last 28 days.

2. Relative Abundance (Mean Value) of Most Abundant Bacterial Phylum Before and After VSL#3 Probiotic Administration [Week 0 and Week 4]

   From week 0 to week 4, change in the relative abundance (percentage) of most common types of bacteria phyla normally found in the lower GI track (e.g. Firmicutes, Bacteroidetes, Actinobacteria and Proteobacteria) after ingesting VSL#3 in the presence or absence of omeprazole. Stool samples are assessed.

3. Change in Peak Intensity of the Metabolite 1H-Indole-4-carbaldehyde Before and After VSL#3 Probiotic Administration (Omeprazole and VSL #3). [Week 0 and Week 4]

   From week 0 to week 4, relative change in metabolites (e.g. short chain fatty acids, bile acid derivatives, flavonoids, amino acids) found in the GI track by mass spectrometry after ingesting VSL#3. Serum samples are assessed. MZ = mass/charge ratio; RT = retention time. MZ/RT data were obtained by mass spectrometry analysis. This is a metabolite of interest for the Omeprazole and VSL#3 group only.

4. Change in Peak Intensity of Metabolites of Interest Before and After VSL#3 Probiotic Administration (Placebo and VSL#3 Group). [Week 0 and Week 4]

   From week 0 to week 4, relative change in metabolites (e.g. short chain fatty acids, bile acid derivatives, flavonoids, amino acids) found in the GI track by mass spectrometry after ingesting VSL#3. Serum samples are assessed. MZ = mass/charge ratio; RT = retention time. MZ/RT data were obtained by mass spectrometry analysis. These are metabolites of interest for the Placebo and VSL#3 group only.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 75 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

• Healthy volunteers ages 18 years and ≤ 75 years.

• Able to visit the study Doctor's office 3 times, answer 3 questionnaires, and provide stools and blood samples.

Exclusion Criteria:

• Gastric cancer, Barrett's esophagus cancer, any gastrointestinal condition, or soy or gluten sensitivity

• Previous abdominal surgery

• Currently pregnant or nursing

• Had H. Pylori Infection

• Diagnosed with any chronic medical condition other than hypertension or hyperlipidemia

• Currently consuming herbs or probiotics

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Stanford University	Palo Alto	California	United States	94304

Sponsors and Collaborators

• Stanford University

Investigators

• Principal Investigator: Aida Habtezion, M.D., Stanford University

Study Documents (Full-Text)

• Study Protocol - Aug 28, 2018
• Statistical Analysis Plan - Sep 13, 2019

More Information

Publications

None provided.

• Responsible Party: Aida Habtezion, Associate Professor of Medicine (Gastroenterology and Hepatology), Stanford University
• ClinicalTrials.gov Identifier: NCT03327051
• Other Study ID Numbers: 41681
• First Posted: Oct 31, 2017
• Last Update Posted: Mar 11, 2020
• Last Verified: Feb 1, 2020

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: Yes
• Additional relevant MeSH terms: Omeprazole

Study Results

Participant Flow

Recruitment Details	Participants attended an initial study visit at week -2, followed by a baseline visit at week 0, and a final visit at week 4.

Arm/Group Title	Omeprazole and VSL #3	Placebo and VSL #3
Arm/Group Description	Proton pump inhibitor (Omeprazole) and VSL #3 Probiotics	Placebo and VSL #3 Probiotics
Period Title: Overall Study
STARTED	19	20
Received Treatment	16	16
Attended Visit 2 (Week 0)	15	15
COMPLETED	14	15
NOT COMPLETED	5	5

Baseline Characteristics

Arm/Group Title	Omeprazole and VSL #3	Placebo and VSL #3	Total
Arm/Group Description	Proton pump inhibitor (Omeprazole) and VSL #3 Probiotics	Placebo and VSL #3 Probiotics	Total of all reporting groups
Overall Participants	15	15	30
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	36 (13)	37 (12)	37 (12)
Sex: Female, Male (Count of Participants)
Female	11 73.3%	9 60%	20 66.7%
Male	4 26.7%	6 40%	10 33.3%
Race/Ethnicity, Customized (Count of Participants)
Hispanic / White	3 20%	2 13.3%	5 16.7%
Hispanic / Other	2 13.3%	1 6.7%	3 10%
NonHispanic / White	7 46.7%	6 40%	13 43.3%
NonHispanic / Other	0 0%	1 6.7%	1 3.3%
NonHispanic / Asian	2 13.3%	4 26.7%	6 20%
NonHispanic / Black or African American	1 6.7%	0 0%	1 3.3%
NonHispanic / Native Hawaiian / Pacific Islander	0 0%	1 6.7%	1 3.3%
Region of Enrollment (Count of Participants)
United States	15 100%	15 100%	30 100%
Relative Abundance of Probiotic Strains (percentage of abundance) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [percentage of abundance]	0.3653 (0.407)	0.5875 (0.5691)	0.4764 (0.4907)
Number of participants experiencing gastro-intestinal symptoms. (Count of Participants)
Bloating	1 6.7%	3 20%	4 13.3%
Flatulence	1 6.7%	0 0%	1 3.3%
Diarrhea	1 6.7%	0 0%	1 3.3%

Outcome Measures

1. Primary Outcome

Title	Relative Abundance of VSL#3 Probiotic Bacterial Strains When Ingested in the Presence or Absence of the Proton Pump Inhibitor (PPI) Omeprazole at Week 4.
Description	Relative abundance is reported as the percent of combined VSL #3 probiotic bacteria strains in the bacteria sample (S. thermophiles, B. breve, B. longum, B. infantis, L. acidophilus, L. plantarum, L. paracasei, L. delbrueckii subsp. bulgaricus) following their ingestion in the presence or absence of the gastric acid suppression drug omeprazole. Stool samples were assessed.
Time Frame	Week 4

Outcome Measure Data

Analysis Population Description

Participants who attended the week 4 visit are included in the analysis.

Arm/Group Title	Omeprazole and VSL #3	Placebo and VSL #3
Arm/Group Description	Proton pump inhibitor (Omeprazole) and VSL #3 Probiotics	Placebo and VSL #3 Probiotics
Measure Participants	14	15
Mean (Standard Deviation) [percentage of abundance]	1.002 (0.8403)	0.8186 (0.5234)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Omeprazole and VSL #3
	Comments	Within group difference between week 0 and week 4 was analyzed.
	Type of Statistical Test	Other
	Comments	An increase in relative abundance of VSL3 bacterial strains at week 4 compared to week 0 (baseline) is considered significant if p<0.05.
Statistical Test of Hypothesis	p-Value	0.04
	Comments
	Method	ANOVA
	Comments	Two-way ANOVA with Bonferroni post-test was used for multi-variable analysis

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo and VSL #3
	Comments	Within group difference between week 0 and week 4 was analyzed.
	Type of Statistical Test	Other
	Comments	An increase in relative abundance of VSL3 bacterial strains at week 4 compared to week 0 (baseline) is considered significant if p<0.05.
Statistical Test of Hypothesis	p-Value	>0.99
	Comments
	Method	ANOVA
	Comments	Two-way ANOVA with Bonferroni post-test was used for multi-variable analysis

2. Secondary Outcome

Title	Number of Participants With Symptoms Related to VSL#3 Treatment.
Description	Participants were asked to report symptoms of gastro-intestinal discomfort experienced within the last 28 days.
Time Frame	Week 0 through Week 4

Outcome Measure Data

Analysis Population Description

Participants who attended the week 4 visit are included in the analysis.

Arm/Group Title	Omeprazole and VSL #3	Placebo and VSL #3
Arm/Group Description	Proton pump inhibitor (Omeprazole) and VSL #3 Probiotics	Placebo and VSL #3 Probiotics
Measure Participants	14	15
Bloating	0 0%	2 13.3%
Flatulence	2 13.3%	0 0%
Diarrhea	2 13.3%	0 0%

3. Secondary Outcome

Title	Relative Abundance (Mean Value) of Most Abundant Bacterial Phylum Before and After VSL#3 Probiotic Administration
Description	From week 0 to week 4, change in the relative abundance (percentage) of most common types of bacteria phyla normally found in the lower GI track (e.g. Firmicutes, Bacteroidetes, Actinobacteria and Proteobacteria) after ingesting VSL#3 in the presence or absence of omeprazole. Stool samples are assessed.
Time Frame	Week 0 and Week 4

Outcome Measure Data

Analysis Population Description

Participants who attended the week 4 visit are included in the analysis.

Arm/Group Title	Omeprazole and VSL #3	Placebo and VSL #3
Arm/Group Description	Proton pump inhibitor (Omeprazole) and VSL #3 Probiotics	Placebo and VSL #3 Probiotics
Measure Participants	14	15
Bacteroidetes at Week 0	66.4 (15.1)	65.6 (11.3)
Bacteroidetes at Week 4	66.2 (15.0)	68.1 (10.2)
Firmicutes at Week 0	25.6 (9.6)	27.2 (9.6)
Firmicutes at Week 4	25.7 (12.6)	25.0 (8.3)
Proteobacteria at Week 0	4.1 (6.0)	2.7 (1.8)
Proteobacteria at Week 4	3.12 (3.7)	2.7 (2.4)
Actinobacteria at Week 0	2.5 (2.5)	3.2 (2.8)
Actinobacteria at Week 4	3.7 (3.7)	3.2 (1.9)

4. Secondary Outcome

Title	Change in Peak Intensity of the Metabolite 1H-Indole-4-carbaldehyde Before and After VSL#3 Probiotic Administration (Omeprazole and VSL #3).
Description	From week 0 to week 4, relative change in metabolites (e.g. short chain fatty acids, bile acid derivatives, flavonoids, amino acids) found in the GI track by mass spectrometry after ingesting VSL#3. Serum samples are assessed. MZ = mass/charge ratio; RT = retention time. MZ/RT data were obtained by mass spectrometry analysis. This is a metabolite of interest for the Omeprazole and VSL#3 group only.
Time Frame	Week 0 and Week 4

Outcome Measure Data

Analysis Population Description

Participants in the Omeprazole and VSL#3 group who attended the week 4 visit are included in the analysis.

Arm/Group Title	Omeprazole and VSL #3
Arm/Group Description	Proton pump inhibitor (Omeprazole) and VSL #3 Probiotics
Measure Participants	14
1H-Indole-4-carbaldehyde at Week 0	80809.5 (118044.6)
1H-Indole-4-carbaldehyde at Week 4	286707.9 (567693.1)

5. Secondary Outcome

Title	Change in Peak Intensity of Metabolites of Interest Before and After VSL#3 Probiotic Administration (Placebo and VSL#3 Group).
Description	From week 0 to week 4, relative change in metabolites (e.g. short chain fatty acids, bile acid derivatives, flavonoids, amino acids) found in the GI track by mass spectrometry after ingesting VSL#3. Serum samples are assessed. MZ = mass/charge ratio; RT = retention time. MZ/RT data were obtained by mass spectrometry analysis. These are metabolites of interest for the Placebo and VSL#3 group only.
Time Frame	Week 0 and Week 4

Outcome Measure Data

Analysis Population Description

Participants in the Placebo and VSL#3 group who attended the week 4 visit are included in the analysis.

Arm/Group Title	Placebo and VSL #3
Arm/Group Description	Placebo and VSL #3 Probiotics
Measure Participants	15
11-OXOURSOLIC ACID ACETATE at Week 0	95819.8 (146506.5)
11-OXOURSOLIC ACID ACETATE at Week 4	4726.2 (18243.3)
FA(14:0) at Week 0	539032.9 (519162.2)
FA(14:0) at Week 4	249632.3 (219622.8)
Iloprost S-isomer at Week 0	87765.6 (189360.0)
Iloprost S-isomer at Week 4	22405.5 (63899.1)

Adverse Events

Time Frame	6 weeks
Arm/Group Title	Omeprazole and VSL #3		Placebo and VSL #3
Arm/Group Description	Proton pump inhibitor (Omeprazole) and VSL #3 Probiotics		Placebo and VSL #3 Probiotics
All Cause Mortality
	Omeprazole and VSL #3		Placebo and VSL #3
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/19 (0%)		0/20 (0%)
Serious Adverse Events
	Omeprazole and VSL #3		Placebo and VSL #3
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/19 (0%)		0/20 (0%)
Other (Not Including Serious) Adverse Events
	Omeprazole and VSL #3		Placebo and VSL #3
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	7/19 (36.8%)		9/20 (45%)
Gastrointestinal disorders
Nausea	1/19 (5.3%)	3	2/20 (10%)	2
Increased stool frequency	1/19 (5.3%)	1	0/20 (0%)	0
Bloating	1/19 (5.3%)	1	4/20 (20%)	7
Flatulence	2/19 (10.5%)	2	1/20 (5%)	1
Diarrhea	1/19 (5.3%)	1	1/20 (5%)	1
Immune system disorders
Allergic reaction	1/19 (5.3%)	1	0/20 (0%)	0
Musculoskeletal and connective tissue disorders
Leg pain	0/19 (0%)	0	1/20 (5%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.