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

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ClinicalTrials.gov Identifier: NCT04118699
Recruitment Status : Recruiting
First Posted : October 8, 2019
Last Update Posted : September 25, 2020
Sponsor:
Collaborator:
ASKA Pharmaceutical Co., Ltd.
Information provided by (Responsible Party):
Yokohama City University

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

Condition or disease Intervention/treatment Phase
Chronic Intestinal Pseudo-obstruction Drug: Rifaximin oral tablet Drug: Placebo oral tablet Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 12 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
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
Actual Study Start Date : December 25, 2019
Estimated Primary Completion Date : November 2021
Estimated Study Completion Date : January 2022


Arm Intervention/treatment
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 Name: 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




Primary Outcome Measures :
  1. 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.

  2. 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.


Secondary Outcome Measures :
  1. 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.

  2. 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.

  3. 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.

  4. 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''.

  5. 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).

  6. 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).

  7. 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.

  8. 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''.

  9. Patient satisfaction score [ Time Frame: At the end of the administration (4 weeks) ]
    % of the "satisfaction" ratio in patient satisfaction score

  10. 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.

  11. 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

  12. 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

  13. 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

  14. 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

  15. 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

  16. 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

  17. 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


Other Outcome Measures:
  1. 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

  2. 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.

  3. 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.

  4. Adverse events [ Time Frame: From the start of administration to 8 weeks after the end of administration ]
    Incidence of adverse events

  5. 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

  6. 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

  7. 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.

  8. 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.

  9. 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.

  10. 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.

  11. 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.

  12. 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.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   20 Years to 74 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04118699


Contacts
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Contact: Hidenori Ohkubo, MD.,PhD. +81-45-787-2800 ext 2640 ohkuboh@yokohama-cu.ac.jp
Contact: Atsushi Nakajima, MD.,PhD. +81-45-787-2800 ext 2640 nakajima-tky@umin.ac.jp

Locations
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Japan
Yokohama city university Recruiting
Yokohama, Kanagawa, Japan, 236-0004
Contact: Hidenori Ohkubo, MD., PhD.    +81-45-787-2800 ext 2640    ohkukbo@yokohama-cu.ac.jp   
Sponsors and Collaborators
Yokohama City University
ASKA Pharmaceutical Co., Ltd.
Publications:
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Responsible Party: Yokohama City University
ClinicalTrials.gov Identifier: NCT04118699    
Other Study ID Numbers: YCU19001
First Posted: October 8, 2019    Key Record Dates
Last Update Posted: September 25, 2020
Last Verified: September 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Yokohama City University:
Rifaximin
L-105
phase 2 trial
CIPO
small intestinal bacterial overgrowth
systemic scleroderma
Additional relevant MeSH terms:
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Intestinal Pseudo-Obstruction
Ileus
Intestinal Obstruction
Intestinal Diseases
Gastrointestinal Diseases
Digestive System Diseases
Rifaximin
Anti-Bacterial Agents
Anti-Infective Agents
Gastrointestinal Agents