Clinical trial NCT04118699: 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
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Chronic Intestinal Pseudo-obstruction
Keywords: Rifaximin
L-105
phase 2 trial
CIPO
small intestinal bacterial overgrowth
systemic scleroderma
Lead sponsor: Yokohama City University
Sponsor class: OTHER
Collaborators: name: ASKA Pharmaceutical Co., Ltd.
First posted: 2019-10-08
Enrollment: 12
Sex: ALL
Minimum age (years): 20
Maximum age (years): 74
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Improvement ratio (%) in abdominal bloating score in Global Symptomatic Score (GSS)
timeFrame: at the end of administration (4 weeks)
measure: Improvement ratio (%) in Gastrointestinal (GI) symptoms score
timeFrame: at the end of administration (4 weeks)
Secondary outcomes:
measure: Changes of the improvement ratio (%) in abdominal bloating score
timeFrame: Before, 2 and 4 weeks after administration;and 4 and 8 weeks after the end of administration
measure: Changes of abdominal bloating score
timeFrame: Before, 2 and 4 weeks after administration;and 4 and 8 weeks after the end of administration
measure: Changes of the improvement ratio (%) in gastrointestinal symptoms score
timeFrame: Before, 2 and 4 weeks after administration;and 4 and 8 weeks after the end of administration
measure: Changes of the "good" ratio (%) in gastrointestinal symptoms score
timeFrame: Before, 2 and 4 weeks after administration;and 4 and 8 weeks after the end of administration
measure: Changes of each score in Global Symptomatic Score other than abdominal bloating score
timeFrame: Before, 2 and 4 weeks after administration;and 4 and 8 weeks after the end of administration
measure: Changes of total scores in Global Symptomatic Score
timeFrame: Before, 2 and 4 weeks after administration;and 4 and 8 weeks after the end of administration
measure: Changes of the improvement ratio (%) in General health condition (symptoms) score
timeFrame: Before, 2 and 4 weeks after administration;and 4 and 8 weeks after the end of administration
measure: Changes of the "good" ratio (%) in General health condition (symptoms) score
timeFrame: Before, 2 and 4 weeks after administration;and 4 and 8 weeks after the end of administration
measure: Patient satisfaction score
timeFrame: At the end of the administration (4 weeks)
measure: Changes of Short Form (SF)-8 health survey score
timeFrame: Before, 2 and 4 weeks after administration;and 4 and 8 weeks after the end of administration
measure: Small intestinal volume measured by abdominal CT scan
timeFrame: Before, 2 and 4 weeks after administration;and 4 and 8 weeks after the end of administration
measure: Changes from baseline of serum albumin level
timeFrame: Before, 2 and 4 weeks after administration;and 4 and 8 weeks after the end of administration
measure: Changes from baseline of prealbumin (transthyretin)
timeFrame: Before, 2 and 4 weeks after administration;and 4 and 8 weeks after the end of administration
measure: Changes from baseline of cholinesterase
timeFrame: Before, 2 and 4 weeks after administration;and 4 and 8 weeks after the end of administration
measure: Changes from baseline of folic acid
timeFrame: Before, 2 and 4 weeks after administration;and 4 and 8 weeks after the end of administration
measure: Changes from baseline of vitamin B12 (cobalamin)
timeFrame: Before, 2 and 4 weeks after administration;and 4 and 8 weeks after the end of administration
measure: Changes from baseline of serum iron
timeFrame: Before, 2 and 4 weeks after administration;and 4 and 8 weeks after the end of administration
Other outcomes:
measure: Small intestinal bacterial overgrowth (SIBO) in a glucose-hydrogen breath test
timeFrame: Before, 4 weeks after administration;and 8 weeks after the end of administration
measure: Changes of Serum endotoxin activity
timeFrame: Before, 2 and 4 weeks after administration;and 4 and 8 weeks after the end of administration
measure: Fecal test (intestinal flora)
timeFrame: Before and 4 weeks after administration
measure: Adverse events
timeFrame: From the start of administration to 8 weeks after the end of administration
measure: Changes from baseline of hematological parameters
timeFrame: Before, 2 and 4 weeks after administration; and 4 and 8 weeks after the end of administration
measure: Changes from the baseline of total protein
timeFrame: Before, 2 and 4 weeks after administration; and 4 and 8 weeks after the end of administration
measure: Changes from the baseline of liver function
timeFrame: Before, 2 and 4 weeks after administration; and 4 and 8 weeks after the end of administration
measure: Changes from the baseline of renal function
timeFrame: Before, 2 and 4 weeks after administration; and 4 and 8 weeks after the end of administration
measure: Changes from the baseline of electrolytes
timeFrame: Before, 2 and 4 weeks after administration; and 4 and 8 weeks after the end of administration
measure: Changes from the baseline of blood lipid level
timeFrame: Before, 2 and 4 weeks after administration; and 4 and 8 weeks after the end of administration
measure: Changes from the baseline of C reactive protein
timeFrame: Before, 2 and 4 weeks after administration; and 4 and 8 weeks after the end of administration
measure: Changes from the baseline of serum glucose level
timeFrame: Before, 2 and 4 weeks after administration; and 4 and 8 weeks after the end of administration
Locations:
city: Yokohama
country: Japan
facility: Yokohama city university
state: Kanagawa
Study officials:
References:
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.
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.