Efficacy and Safety of Rifaximin for Patients With Chronic Intestinal Pseudo-obstruction: a Phase 2 Trial

June 18, 2021 updated by: Yokohama City University

Efficacy and Safety of Rifaximin for Patients With Chronic Intestinal Pseudo-obstruction: a Single Center, Randomized, Placebo Controlled, Double-blind Phase 2 Trial

The objective of the study is to investigate efficacy and safety of rifaximin (L-105) in patients with chronic idiopathic intestinal pseudo-obstruction(CIIPO) or patients with chronic intestinal pseudo-obstruction (CIPO), secondary to systemic scleroderma

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Active, not recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

This is a placebo-controlled, randomized, double-blind, parallel group, comparative study, when patients with chronic idiopathic intestinal pseudo-obstruction(CIIPO) or patients with chronic intestinal pseudo-obstruction (CIPO), secondary to the onset of systemic scleroderma, are administered rifaximin at 400 mg 3 times daily for 4 weeks. In addition, the time course of symptoms of the patients are to be confirmed for 8 weeks after the end of administration.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Anticipated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
12

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Japan
    • Kanagawa
      • Yokohama, Kanagawa, Japan, 236-0004
        • Yokohama city university

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

16 years to 70 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Outpatients aged ≥20 and <75 on the day of informed consent (IC)
  • Patients with CIIPO (designated intractable disease 99) at enrollment, satisfying all the criteria specified in (1) to (7) of the CIIPO Diagnostic Criteria issued in 2014 by the MHLW Research Group, or patients with CIPO, secondary to systemic scleroderma, satisfying all the same criteria specified in (1) to (6)
  • Patients' levels of abdominal bloating symptoms, 4 scales of GSS, should be score 2 or 3 at the time of IC acquisition and enrollment.

Exclusion Criteria:

  • Patients with malignant diseases (excluding those whose symptoms are stable and who do not require aggressive treatments such as chemotherapy and/or surgical therapy)
  • Patients with psychiatric diseases (excluding those whose symptoms are stable, and the investigator or coinvestigator concludes that efficacy of the patient can be assessed without any issue)
  • Patients with severe diabetes within 5 weeks before enrollment (HbA1c >10%)
  • Patients who have already had gastrostomy (including percutaneousendoscopic gastro -jejunostomy, PEG-J), enterostomy, or colostomy
  • Patients who underwent intestinal decompression therapy not associated with surgical procedures (trans-nasal ileus tube) within 4weeks before enrollment
  • Patients who used antimicrobials, antiparasitics or antifungals (excluding topical use) within 4 weeks before enrollment
  • Patients who have changed the doses of the following concomitantly administered drugs within 4 weeks before enrollment: mosapride, daikenchuto, metoclopramide, acotiamide
  • Patients with severe hepatic disorders within 5 weeks before enrollment (who meet either one of the following criteria: AST≥ 5 x the upper limit of the common reference value specified in the Japanese Committee for Clinical Laboratory Standards (JCCLS), ALT≥ 5 x the upper limit of the common reference value specified in JCCLS, total bilirubin ≥ 3 x the upper limit of the common reference value specified in JCCLS, decompensated hematic cirrhosis, or jaundice)
  • Patients who are pregnant, breastfeeding, possibly pregnant, or those who wish to become pregnant
  • Patients with a previous history of hypersensitivity to any investigational product ingredients
  • Patients with active tuberculosis
  • Patients who participated in other clinical trial (including a trial with an investigational product) within 12 weeks before this enrollment and who received an intervention with a test drug
  • Other patients whose participation in the trial is concluded to be inappropriate by the investigator or coinvestigator

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Rifaximin
Two tablets of the investigational product per dosing (400 mg of rifaximin) are orally administered 3 times daily for 4 weeks.
Drug: Rifaximin oral tablet
Patients with chronic idiopathic intestinal pseudo-obstruction (CIIPO) or patients with chronic intestinal pseudo-obstruction (CIPO), secondary to systemic scleroderma, are administered investigational product (rifaximin) for 4 weeks
Other Names:
  • L-105
Placebo Comparator: Placebo
Two tablets of the placebo are orally administered 3 times daily for 4 weeks.
Drug: Placebo oral tablet
Patients with chronic idiopathic intestinal pseudo-obstruction (CIIPO) or patients with chronic intestinal pseudo-obstruction (CIPO), secondary to systemic scleroderma, are administered placebo for 4 weeks

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Improvement ratio (%) in abdominal bloating score in Global Symptomatic Score (GSS)
Time Frame: at the end of administration (4 weeks)
Abdominal bloating score in Global Symptomatic Score (GSS) is used. GSS is a 4-point Likert scale ranging from 0 (no symptom) to 3 (severe, incapacitating with inability to perform normal activities), with lower scores reflecting better symptoms. Score 0 or 1 is defined as improvement.
at the end of administration (4 weeks)
Improvement ratio (%) in Gastrointestinal (GI) symptoms score
Time Frame: at the end of administration (4 weeks)
Gastrointestinal score (GI score) is a 5-point Likert scale (0; greatly improved, 1; improved, 2; no change, 3; worsened, 4; severely worsened), with lower scores reflecting more improved symptoms. Score 0 or 1 is defined as improvement.
at the end of administration (4 weeks)

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Changes of the improvement ratio (%) in abdominal bloating score
Time Frame: Before, 2 and 4 weeks after administration;and 4 and 8 weeks after the end of administration
Abdominal bloating score in Global Symptomatic Score (GSS) is used. GSS is a 4-point likert scale ranging from 0 (no symptom) to 3 (severe, incapacitating with inability to perform normal activities), with lower scores reflecting better symptoms. Score 0 or 1 is defined as improvement.
Before, 2 and 4 weeks after administration;and 4 and 8 weeks after the end of administration
Changes of abdominal bloating score
Time Frame: Before, 2 and 4 weeks after administration;and 4 and 8 weeks after the end of administration
Abdominal bloating score in Global Symptomatic Score (GSS) is used. GSS is a 4-point likert scale ranging from 0 (no symptom) to 3 (severe, incapacitating with inability to perform normal activities), with lower scores reflecting better symptoms.
Before, 2 and 4 weeks after administration;and 4 and 8 weeks after the end of administration
Changes of the improvement ratio (%) in gastrointestinal symptoms score
Time Frame: Before, 2 and 4 weeks after administration;and 4 and 8 weeks after the end of administration
Gastrointestinal score (GI score), a 5-point likert scale (0; greatly improved, 1; improved, 2; no change, 3; worsened, 4; severely worsened), with lower scores reflecting more improved symptoms, is used. Score 0 or 1 is defined as improvement.
Before, 2 and 4 weeks after administration;and 4 and 8 weeks after the end of administration
Changes of the "good" ratio (%) in gastrointestinal symptoms score
Time Frame: Before, 2 and 4 weeks after administration;and 4 and 8 weeks after the end of administration
Gastrointestinal score (GI score), 5-point likert scale (0; very good, 1; good, 2; average, 3; bad, 4; extremely bad), with lower scores reflecting better conditions, is used. Score 0 or 1 is defined as ''good''.
Before, 2 and 4 weeks after administration;and 4 and 8 weeks after the end of administration
Changes of each score in Global Symptomatic Score other than abdominal bloating score
Time Frame: Before, 2 and 4 weeks after administration;and 4 and 8 weeks after the end of administration
Global Symptomatic Score (GSS), a 4-point likert scale ranging from 0 (no symptom) to 3 (severe), of the following symptoms are assessed; (a. diarrhea, b. epigastric pain/ discomfort, c. pain in the lower quadrant/discomfort, d. tenderness, e. nausea, f. vomiting).
Before, 2 and 4 weeks after administration;and 4 and 8 weeks after the end of administration
Changes of total scores in Global Symptomatic Score
Time Frame: Before, 2 and 4 weeks after administration;and 4 and 8 weeks after the end of administration
Sum of Global Symptomatic Score (GSS) of the following 7 symptoms, 0 to maximum of 21, are assessed; (a. diarrhea, b. epigastric pain/discomfort, c. abdominal distention, d. pain in the lower quadrant/discomfort, e. tenderness, f. nausea, g. vomiting).
Before, 2 and 4 weeks after administration;and 4 and 8 weeks after the end of administration
Changes of the improvement ratio (%) in General health condition (symptoms) score
Time Frame: Before, 2 and 4 weeks after administration;and 4 and 8 weeks after the end of administration
General health condition (symptoms) score, a 5-point likert scale (0; greatly improved, 1; improved, 2; no change, 3; worsened, 4; severely worsened), with lower scores reflecting more improved symptoms, is used. Score 0 or 1 is defined as improvement.
Before, 2 and 4 weeks after administration;and 4 and 8 weeks after the end of administration
Changes of the "good" ratio (%) in General health condition (symptoms) score
Time Frame: Before, 2 and 4 weeks after administration;and 4 and 8 weeks after the end of administration
General health condition (symptoms) score, 5-point scale (0; very good, 1; good, 2; average, 3; bad, 4; extremely bad), with lower scores reflecting better conditions, is used. Score 0 or 1 is defined as ''good''.
Before, 2 and 4 weeks after administration;and 4 and 8 weeks after the end of administration
Patient satisfaction score
Time Frame: At the end of the administration (4 weeks)
% of the "satisfaction" ratio in patient satisfaction score
At the end of the administration (4 weeks)
Changes of Short Form (SF)-8 health survey score
Time Frame: Before, 2 and 4 weeks after administration;and 4 and 8 weeks after the end of administration
SF-8(short form-8), a self-reporting health survey ranging from 8 to maximum of 42, with lower scores reflecting better conditions, is used.
Before, 2 and 4 weeks after administration;and 4 and 8 weeks after the end of administration
Small intestinal volume measured by abdominal CT scan
Time Frame: Before, 2 and 4 weeks after administration;and 4 and 8 weeks after the end of administration
Changes of small intestinal volume measured by abdominal CT scan
Before, 2 and 4 weeks after administration;and 4 and 8 weeks after the end of administration
Changes from baseline of serum albumin level
Time Frame: Before, 2 and 4 weeks after administration;and 4 and 8 weeks after the end of administration
Serum albumin level is calculated for nutritional assessment
Before, 2 and 4 weeks after administration;and 4 and 8 weeks after the end of administration
Changes from baseline of prealbumin (transthyretin)
Time Frame: Before, 2 and 4 weeks after administration;and 4 and 8 weeks after the end of administration
Prealbumin (transthyretin) is calculated for nutritional assessment
Before, 2 and 4 weeks after administration;and 4 and 8 weeks after the end of administration
Changes from baseline of cholinesterase
Time Frame: Before, 2 and 4 weeks after administration;and 4 and 8 weeks after the end of administration
Cholinesterase is calculated for nutritional assessment
Before, 2 and 4 weeks after administration;and 4 and 8 weeks after the end of administration
Changes from baseline of folic acid
Time Frame: Before, 2 and 4 weeks after administration;and 4 and 8 weeks after the end of administration
Folic acid is calculated for nutritional assessment
Before, 2 and 4 weeks after administration;and 4 and 8 weeks after the end of administration
Changes from baseline of vitamin B12 (cobalamin)
Time Frame: Before, 2 and 4 weeks after administration;and 4 and 8 weeks after the end of administration
Vitamin B12 (cobalamin) is calculated for nutritional assessment
Before, 2 and 4 weeks after administration;and 4 and 8 weeks after the end of administration
Changes from baseline of serum iron
Time Frame: Before, 2 and 4 weeks after administration;and 4 and 8 weeks after the end of administration
Serum iron is calculated for nutritional assessment
Before, 2 and 4 weeks after administration;and 4 and 8 weeks after the end of administration

Other Outcome Measures

Other Outcome Measures

For clinical trials, a planned measurement described in the protocol that is used to determine the effect of an intervention/treatment on participants. For observational studies, a measurement or observation that is used to describe patterns of diseases or traits, or associations with exposures, risk factors, or treatment. Types of outcome measures include primary outcome measure and secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Small intestinal bacterial overgrowth (SIBO) in a glucose-hydrogen breath test
Time Frame: Before, 4 weeks after administration;and 8 weeks after the end of administration
Elimination rate of SIBO in a glucose-hydrogen breath test
Before, 4 weeks after administration;and 8 weeks after the end of administration
Changes of Serum endotoxin activity
Time Frame: Before, 2 and 4 weeks after administration;and 4 and 8 weeks after the end of administration
Serum endotoxin activity, ranging from 0.00-1.00, is assessed using EAA® (endotoxin activity assay, Toray Medical Co., Ltd.), FDA approved rapid whole blood assay for detection of human endotoxemia. 0.00-0.39 means low level, 0.40-0.59 means middle level, and ≥0.60 means high level.
Before, 2 and 4 weeks after administration;and 4 and 8 weeks after the end of administration
Fecal test (intestinal flora)
Time Frame: Before and 4 weeks after administration
Changes of intestinal flora detected by 16SrDNA amplicon analysis using next generation sequencing.
Before and 4 weeks after administration
Adverse events
Time Frame: From the start of administration to 8 weeks after the end of administration
Incidence of adverse events
From the start of administration to 8 weeks after the end of administration
Changes from baseline of hematological parameters
Time Frame: Before, 2 and 4 weeks after administration; and 4 and 8 weeks after the end of administration
Hematological parameters (red blood cell count, hematocrit, white blood cell count, platelet count) are calculated for safety assessment
Before, 2 and 4 weeks after administration; and 4 and 8 weeks after the end of administration
Changes from the baseline of total protein
Time Frame: Before, 2 and 4 weeks after administration; and 4 and 8 weeks after the end of administration
Total protein is calculated for safety assessment
Before, 2 and 4 weeks after administration; and 4 and 8 weeks after the end of administration
Changes from the baseline of liver function
Time Frame: Before, 2 and 4 weeks after administration; and 4 and 8 weeks after the end of administration
Liver function parameters (aspartate aminotransferase, alanine aminotransferase, gamma-glutamyl transpeptidase, alkaline phosphatase, total bilirubin) are calculated for safety assessment.
Before, 2 and 4 weeks after administration; and 4 and 8 weeks after the end of administration
Changes from the baseline of renal function
Time Frame: Before, 2 and 4 weeks after administration; and 4 and 8 weeks after the end of administration
Creatinine and blood urea nitrogen are calculated for safety assessment.
Before, 2 and 4 weeks after administration; and 4 and 8 weeks after the end of administration
Changes from the baseline of electrolytes
Time Frame: Before, 2 and 4 weeks after administration; and 4 and 8 weeks after the end of administration
Electrolytes (sodium, potassium, chlorine, calcium) are calculated for safety assessment.
Before, 2 and 4 weeks after administration; and 4 and 8 weeks after the end of administration
Changes from the baseline of blood lipid level
Time Frame: Before, 2 and 4 weeks after administration; and 4 and 8 weeks after the end of administration
Blood lipid level (total cholesterol, triglyceride, and high-density lipoprotein cholesterol) is calculated for safety assessment.
Before, 2 and 4 weeks after administration; and 4 and 8 weeks after the end of administration
Changes from the baseline of C reactive protein
Time Frame: Before, 2 and 4 weeks after administration; and 4 and 8 weeks after the end of administration
C reactive protein is calculated for safety assessment.
Before, 2 and 4 weeks after administration; and 4 and 8 weeks after the end of administration
Changes from the baseline of serum glucose level
Time Frame: Before, 2 and 4 weeks after administration; and 4 and 8 weeks after the end of administration
Serum glucose level is calculated for safety assessment.
Before, 2 and 4 weeks after administration; and 4 and 8 weeks after the end of administration

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Yokohama City University

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
ASKA Pharmaceutical Co., Ltd.

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
December 25, 2019

Primary Completion (Anticipated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
November 1, 2021

Study Completion (Anticipated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
January 1, 2022

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
September 23, 2019

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
October 4, 2019

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
October 8, 2019

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
June 21, 2021

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
June 18, 2021

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
June 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • YCU19001

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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