Proton Pump Inhibitors and Dysbiosis in Cirrhosis

• Sponsor: Hunter Holmes Mcguire Veteran Affairs Medical Center (U.S. Fed)
• Overall Status: Completed
• CT.gov ID: NCT01458990
• Collaborator: (none)
• Enrollment: 60
• Location: 1
• Arms: 2
• Duration (Months): 76.1
• Patients Per Site Per Month: 0.8

Study Details

Study Description

Brief Summary

The purpose of this study is to find out whether the use of medications that suppress acid in your stomach can change the composition of your bowel bacteria.

Condition or Disease	Intervention/Treatment	Phase
Cirrhosis; Healthy	Drug: Omeprazole	N/A

Study Design

• Study Type: Interventional
• Actual Enrollment: 60 participants
• Allocation: Non-Randomized
• Intervention Model: Single Group Assignment
• Intervention Model Description: PPI withdrawal (decompensated patients only) and PPI initiation (compensated and decompensated patients)PPI withdrawal (decompensated patients only) and PPI initiation (compensated and decompensated patients)
• Masking: None (Open Label)
• Primary Purpose: Diagnostic
• Study Start Date: Oct 1, 2011
• Actual Primary Completion Date: Feb 1, 2018
• Actual Study Completion Date: Feb 1, 2018

Arms and Interventions

Arm	Intervention/Treatment
Experimental: PPI inititation Adding 40mg omeprazole QD for 14 days	Drug: Omeprazole; 20mg PO BID for 20 days
Active Comparator: PPI withdrawal The intervention here is systematically withdrawing chronic PPI for 14 days	Drug: Omeprazole; 20mg PO BID for 20 days

Outcome Measures

Primary Outcome Measures

1. Number of Patients With Overgrowth of Oral Microbiota in Their Stool After PPI Therapy Withdrawal or Initiation [2 weeks]

   Analysis at baseline will be compared to that at 2 weeks using Multitagged sequencing. Number of patients with overgrowth of oral microbiota in their stool after PPI therapy withdrawal or initiation were specifically analyzed.

Secondary Outcome Measures

1. Number of Patients With Adverse Events During Initiation or Withdrawal of PPI Therapy [2 weeks]

   Analysis at baseline will be compared to that at 2 weeks. This will be specifically, changes in those with PPI withdrawal compared to those with PPI initiation

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 70 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria for PPI initiation study:

• Cirrhosis not on current PPI or acid suppressive therapy

• No systemic antibiotics or probiotics

Exclusion Criteria for PPI initiation study:

• On systemic antibiotics

• On PPI or acid suppression therapy already

• unable to give informed consent

• Allergy to proton pump inhibitors

Inclusion Criteria for PPI withdrawal study:

• Cirrhosis on current PPI for an FDA-unapproved indication

• No systemic antibiotics or probiotics

Exclusion Criteria for PPI withdrawal study:

• On systemic absorbable antibiotics

• On PPI or acid suppression therapy for an FDA-approved indication

• unable to give informed consent

• unwilling to withdraw PPI

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Hunter Holmes McGuire VA Medical Center	Richmond	Virginia	United States	23249

Sponsors and Collaborators

• Hunter Holmes Mcguire Veteran Affairs Medical Center

Investigators

None specified.

Study Documents (Full-Text)

• Study Protocol - Nov 29, 2017
• Statistical Analysis Plan - Nov 29, 2017

More Information

Publications

None provided.

• Responsible Party: Jasmohan Bajaj, Associate Professor, Hunter Holmes Mcguire Veteran Affairs Medical Center
• ClinicalTrials.gov Identifier: NCT01458990
• Other Study ID Numbers: BAJAJ004
• First Posted: Oct 25, 2011
• Last Update Posted: Mar 19, 2018
• Last Verified: Mar 1, 2018

• Individual Participant Data (IPD) Sharing Statement: Undecided
• Plan to Share IPD: Undecided
• Additional relevant MeSH terms: Liver Cirrhosis; Fibrosis; Omeprazole

Study Results

Participant Flow

Recruitment Details	Participants recruited from McGuire VAMC hepatology clinics

Arm/Group Title	PPI Inititation	PPI Withdrawal
Arm/Group Description	Adding 40mg omeprazole QD for 14 days	The intervention here is systematically withdrawing chronic PPI for 14 days
Period Title: Overall Study
STARTED	45	15
COMPLETED	45	15
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	PPI Inititation	PPI Withdrawal	Total
Arm/Group Description	Adding 40mg omeprazole QD for 14 days	The intervention here is systematically withdrawing chronic PPI for 14 days	Total of all reporting groups
Overall Participants	45	15	60
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	40 88.9%	14 93.3%	54 90%
>=65 years	5 11.1%	1 6.7%	6 10%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	58 (7.6)	59 (6.7)	58 (7.0)
Sex: Female, Male (Count of Participants)
Female	3 6.7%	1 6.7%	4 6.7%
Male	42 93.3%	14 93.3%	56 93.3%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	16 35.6%	6 40%	22 36.7%
White	29 64.4%	9 60%	38 63.3%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
United States	45 100%	15 100%	60 100%

Outcome Measures

1. Primary Outcome

Title	Number of Patients With Overgrowth of Oral Microbiota in Their Stool After PPI Therapy Withdrawal or Initiation
Description	Analysis at baseline will be compared to that at 2 weeks using Multitagged sequencing. Number of patients with overgrowth of oral microbiota in their stool after PPI therapy withdrawal or initiation were specifically analyzed.
Time Frame	2 weeks

Outcome Measure Data

Analysis Population Description

Comparison were made between groups on/off PPI therapy using Linear discriminant analysis effect size (LEFSe) and using the Quantitative Insights Into Microbial Ecology (QIIME) pipeline and also the relative proportion (%) of oral-origin microbiota were studied

Arm/Group Title	PPI Inititation	PPI Withdrawal
Arm/Group Description	Adding 40mg omeprazole QD for 14 days Omeprazole: 20mg PO BID for 20 days	The intervention here is systematically withdrawing chronic PPI for 14 days Omeprazole: 20mg PO BID for 20 days
Measure Participants	45	15
Count of Participants [Participants]	45 100%	15 100%

2. Secondary Outcome

Title	Number of Patients With Adverse Events During Initiation or Withdrawal of PPI Therapy
Description	Analysis at baseline will be compared to that at 2 weeks. This will be specifically, changes in those with PPI withdrawal compared to those with PPI initiation
Time Frame	2 weeks

Outcome Measure Data

Analysis Population Description

No safety or tolerability issues were seen during the study

Arm/Group Title	PPI Initiation	PPI Withdrawal
Arm/Group Description	No safety signals were identified	No safety signals were identified
Measure Participants	45	15
Count of Participants [Participants]	0 0%	0 0%

Adverse Events

Time Frame	During study period of 14 days
Adverse Event Reporting Description	Standard definitions used
Arm/Group Title	PPI Inititation		PPI Withdrawal
Arm/Group Description	Adding 40mg omeprazole QD for 14 days		The intervention here is systematically withdrawing chronic PPI for 14 days
All Cause Mortality
	PPI Inititation		PPI Withdrawal
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/45 (0%)		0/15 (0%)
Serious Adverse Events
	PPI Inititation		PPI Withdrawal
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/45 (0%)		0/15 (0%)
Other (Not Including Serious) Adverse Events
	PPI Inititation		PPI Withdrawal
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/45 (0%)		0/15 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT 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.