Back to resultsEfficacy and Safety of Rifaximin for Patients With Chronic Intestinal Pseudo-obstruction: a Phase 2 Trial
Primary Purpose
Chronic Intestinal Pseudo-obstruction
Status
Unknown status
Phase
Phase 2
Locations
Japan
Study Type
Interventional
Intervention
Rifaximin oral tablet
Placebo oral tablet
Sponsored by
About this trial
This is an interventional treatment trial for Chronic Intestinal Pseudo-obstruction focused on measuring Rifaximin, L-105, phase 2 trial, CIPO, small intestinal bacterial overgrowth, systemic scleroderma
Eligibility Criteria
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
Sites / Locations
- Yokohama city university
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
Rifaximin
Placebo
Arm Description
Two tablets of the investigational product per dosing (400 mg of rifaximin) are orally administered 3 times daily for 4 weeks.
Two tablets of the placebo are orally administered 3 times daily for 4 weeks.
Outcomes
Primary Outcome Measures
Improvement ratio (%) in abdominal bloating score in Global Symptomatic Score (GSS)
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.
Improvement ratio (%) in Gastrointestinal (GI) symptoms score
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.
Secondary Outcome Measures
Changes of the improvement ratio (%) in abdominal bloating score
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.
Changes of abdominal bloating score
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.
Changes of the improvement ratio (%) in gastrointestinal symptoms score
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.
Changes of the "good" ratio (%) in gastrointestinal symptoms score
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''.
Changes of each score in Global Symptomatic Score other than abdominal bloating score
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).
Changes of total scores in Global Symptomatic Score
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).
Changes of the improvement ratio (%) in General health condition (symptoms) score
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.
Changes of the "good" ratio (%) in General health condition (symptoms) score
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''.
Patient satisfaction score
% of the "satisfaction" ratio in patient satisfaction score
Changes of Short Form (SF)-8 health survey score
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.
Small intestinal volume measured by abdominal CT scan
Changes of small intestinal volume measured by abdominal CT scan
Changes from baseline of serum albumin level
Serum albumin level is calculated for nutritional assessment
Changes from baseline of prealbumin (transthyretin)
Prealbumin (transthyretin) is calculated for nutritional assessment
Changes from baseline of cholinesterase
Cholinesterase is calculated for nutritional assessment
Changes from baseline of folic acid
Folic acid is calculated for nutritional assessment
Changes from baseline of vitamin B12 (cobalamin)
Vitamin B12 (cobalamin) is calculated for nutritional assessment
Changes from baseline of serum iron
Serum iron is calculated for nutritional assessment
Full Information
NCT ID
NCT04118699
First Posted
September 23, 2019
Last Updated
June 18, 2021
Sponsor
Yokohama City University
Collaborators
ASKA Pharmaceutical Co., Ltd.
1. Study Identification
Unique Protocol Identification Number
NCT04118699
Brief Title
Efficacy and Safety of Rifaximin for Patients With Chronic Intestinal Pseudo-obstruction: a Phase 2 Trial
Official Title
Efficacy and Safety of Rifaximin for Patients With Chronic Intestinal Pseudo-obstruction: a Single Center, Randomized, Placebo Controlled, Double-blind Phase 2 Trial
Study Type
Interventional
2. Study Status
Record Verification Date
June 2021
Overall Recruitment Status
Unknown status
Study Start Date
December 25, 2019 (Actual)
Primary Completion Date
November 2021 (Anticipated)
Study Completion Date
January 2022 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Yokohama City University
Collaborators
ASKA Pharmaceutical Co., Ltd.
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
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
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Chronic Intestinal Pseudo-obstruction
Keywords
Rifaximin, L-105, phase 2 trial, CIPO, small intestinal bacterial overgrowth, systemic scleroderma
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
12 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Rifaximin
Arm Type
Experimental
Arm Description
Two tablets of the investigational product per dosing (400 mg of rifaximin) are orally administered 3 times daily for 4 weeks.
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Two tablets of the placebo are orally administered 3 times daily for 4 weeks.
Intervention Type
Drug
Intervention Name(s)
Rifaximin oral tablet
Other Intervention Name(s)
L-105
Intervention Description
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
Intervention Type
Drug
Intervention Name(s)
Placebo oral tablet
Intervention Description
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
Primary Outcome Measure Information:
Title
Improvement ratio (%) in abdominal bloating score in Global Symptomatic Score (GSS)
Description
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.
Time Frame
at the end of administration (4 weeks)
Title
Improvement ratio (%) in Gastrointestinal (GI) symptoms score
Description
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.
Time Frame
at the end of administration (4 weeks)
Secondary Outcome Measure Information:
Title
Changes of the improvement ratio (%) in abdominal bloating score
Description
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.
Time Frame
Before, 2 and 4 weeks after administration;and 4 and 8 weeks after the end of administration
Title
Changes of abdominal bloating score
Description
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.
Time Frame
Before, 2 and 4 weeks after administration;and 4 and 8 weeks after the end of administration
Title
Changes of the improvement ratio (%) in gastrointestinal symptoms score
Description
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.
Time Frame
Before, 2 and 4 weeks after administration;and 4 and 8 weeks after the end of administration
Title
Changes of the "good" ratio (%) in gastrointestinal symptoms score
Description
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''.
Time Frame
Before, 2 and 4 weeks after administration;and 4 and 8 weeks after the end of administration
Title
Changes of each score in Global Symptomatic Score other than abdominal bloating score
Description
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).
Time Frame
Before, 2 and 4 weeks after administration;and 4 and 8 weeks after the end of administration
Title
Changes of total scores in Global Symptomatic Score
Description
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).
Time Frame
Before, 2 and 4 weeks after administration;and 4 and 8 weeks after the end of administration
Title
Changes of the improvement ratio (%) in General health condition (symptoms) score
Description
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.
Time Frame
Before, 2 and 4 weeks after administration;and 4 and 8 weeks after the end of administration
Title
Changes of the "good" ratio (%) in General health condition (symptoms) score
Description
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''.
Time Frame
Before, 2 and 4 weeks after administration;and 4 and 8 weeks after the end of administration
Title
Patient satisfaction score
Description
% of the "satisfaction" ratio in patient satisfaction score
Time Frame
At the end of the administration (4 weeks)
Title
Changes of Short Form (SF)-8 health survey score
Description
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.
Time Frame
Before, 2 and 4 weeks after administration;and 4 and 8 weeks after the end of administration
Title
Small intestinal volume measured by abdominal CT scan
Description
Changes of 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
Title
Changes from baseline of serum albumin level
Description
Serum albumin level is calculated for nutritional assessment
Time Frame
Before, 2 and 4 weeks after administration;and 4 and 8 weeks after the end of administration
Title
Changes from baseline of prealbumin (transthyretin)
Description
Prealbumin (transthyretin) is calculated for nutritional assessment
Time Frame
Before, 2 and 4 weeks after administration;and 4 and 8 weeks after the end of administration
Title
Changes from baseline of cholinesterase
Description
Cholinesterase is calculated for nutritional assessment
Time Frame
Before, 2 and 4 weeks after administration;and 4 and 8 weeks after the end of administration
Title
Changes from baseline of folic acid
Description
Folic acid is calculated for nutritional assessment
Time Frame
Before, 2 and 4 weeks after administration;and 4 and 8 weeks after the end of administration
Title
Changes from baseline of vitamin B12 (cobalamin)
Description
Vitamin B12 (cobalamin) is calculated for nutritional assessment
Time Frame
Before, 2 and 4 weeks after administration;and 4 and 8 weeks after the end of administration
Title
Changes from baseline of serum iron
Description
Serum iron is calculated for nutritional assessment
Time Frame
Before, 2 and 4 weeks after administration;and 4 and 8 weeks after the end of administration
Other Pre-specified Outcome Measures:
Title
Small intestinal bacterial overgrowth (SIBO) in a glucose-hydrogen breath test
Description
Elimination rate of SIBO in a glucose-hydrogen breath test
Time Frame
Before, 4 weeks after administration;and 8 weeks after the end of administration
Title
Changes of Serum endotoxin activity
Description
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.
Time Frame
Before, 2 and 4 weeks after administration;and 4 and 8 weeks after the end of administration
Title
Fecal test (intestinal flora)
Description
Changes of intestinal flora detected by 16SrDNA amplicon analysis using next generation sequencing.
Time Frame
Before and 4 weeks after administration
Title
Adverse events
Description
Incidence of adverse events
Time Frame
From the start of administration to 8 weeks after the end of administration
Title
Changes from baseline of hematological parameters
Description
Hematological parameters (red blood cell count, hematocrit, white blood cell count, platelet count) are calculated for safety assessment
Time Frame
Before, 2 and 4 weeks after administration; and 4 and 8 weeks after the end of administration
Title
Changes from the baseline of total protein
Description
Total protein is calculated for safety assessment
Time Frame
Before, 2 and 4 weeks after administration; and 4 and 8 weeks after the end of administration
Title
Changes from the baseline of liver function
Description
Liver function parameters (aspartate aminotransferase, alanine aminotransferase, gamma-glutamyl transpeptidase, alkaline phosphatase, total bilirubin) are calculated for safety assessment.
Time Frame
Before, 2 and 4 weeks after administration; and 4 and 8 weeks after the end of administration
Title
Changes from the baseline of renal function
Description
Creatinine and blood urea nitrogen are calculated for safety assessment.
Time Frame
Before, 2 and 4 weeks after administration; and 4 and 8 weeks after the end of administration
Title
Changes from the baseline of electrolytes
Description
Electrolytes (sodium, potassium, chlorine, calcium) are calculated for safety assessment.
Time Frame
Before, 2 and 4 weeks after administration; and 4 and 8 weeks after the end of administration
Title
Changes from the baseline of blood lipid level
Description
Blood lipid level (total cholesterol, triglyceride, and high-density lipoprotein cholesterol) is calculated for safety assessment.
Time Frame
Before, 2 and 4 weeks after administration; and 4 and 8 weeks after the end of administration
Title
Changes from the baseline of C reactive protein
Description
C reactive protein is calculated for safety assessment.
Time Frame
Before, 2 and 4 weeks after administration; and 4 and 8 weeks after the end of administration
Title
Changes from the baseline of serum glucose level
Description
Serum glucose level is calculated for safety assessment.
Time Frame
Before, 2 and 4 weeks after administration; and 4 and 8 weeks after the end of administration
10. Eligibility
Sex
All
Minimum Age & Unit of Time
20 Years
Maximum Age & Unit of Time
74 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Facility Information:
Facility Name
Yokohama city university
City
Yokohama
State/Province
Kanagawa
ZIP/Postal Code
236-0004
Country
Japan
12. IPD Sharing Statement
Plan to Share IPD
No
Citations:
PubMed Identifier
22710349
Citation
Ohkubo H, Iida H, Takahashi H, Yamada E, Sakai E, Higurashi T, Sekino Y, Endo H, Sakamoto Y, Inamori M, Sato H, Fujimoto K, Nakajima A. An epidemiologic survey of chronic intestinal pseudo-obstruction and evaluation of the newly proposed diagnostic criteria. Digestion. 2012;86(1):12-9. doi: 10.1159/000337528. Epub 2012 Jun 15.
Results Reference
background
PubMed Identifier
18422815
Citation
Parodi A, Sessarego M, Greco A, Bazzica M, Filaci G, Setti M, Savarino E, Indiveri F, Savarino V, Ghio M. Small intestinal bacterial overgrowth in patients suffering from scleroderma: clinical effectiveness of its eradication. Am J Gastroenterol. 2008 May;103(5):1257-62. doi: 10.1111/j.1572-0241.2007.01758.x. Epub 2008 Apr 16.
Results Reference
background
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Efficacy and Safety of Rifaximin for Patients With Chronic Intestinal Pseudo-obstruction: a Phase 2 Trial
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