Effectiveness of Saccharomyces Boulardii for Gastrointestinal Bacterial-overgrowth in Systemic Sclerosis

NCT03692299 | Completed Phase 4 DMC

• 1 other identifier: R-2015-3501-72
• Study Type: interventional
• Target: 39
• Locations: 1 country
• Sites: 1

Brief Summary

Introduction. Autonomic dysfunction, smooth muscle fibrosis and vascular damage lead to small intestinal bacterial overgrowth (SIBO) in Systemic Sclerosis (SSc). SIBO is characterized by diarrhea, abdominal pain, bloating, malabsorption and malnutrition. Aim. To evaluate the efficacy and safety of Saccharomyces boulardii in combination with metronidazole for 2 months for reducing gastrointestinal symptoms (NIH-PROMIS) and preventing bacterial overgrowth (hydrogen breath test) versus the standard treatment in patients with systemic sclerosis. Method. Controlled clinical trial conduct in patients with SSc (ACR-EULAR 2015) who signed informed consent. NIH PROMIS®questionarie will be apply to evaluate gastrointestinal symptoms and classify in not symptomatic, least, mildy, moderately and most symptomatic. Glucose HBT will be apply after 14 hours fast, oral hygiene and 30 days free of antibiotics to evaluate SIBO. Patients with negative HBT and symptoms associated to glucose ingestion will repeat test with lactulose. Patients will be aleatorized into 1. Saccharomyces boulardii, 2. Metronidazole and 3. Metronidazole plus Saccharomyces boulardii. All data will be analyzed using SPSS software. It will be used parametric statistics for normally distributed variables and nonparametric statistics for free distribution.

Conditions

Systemic Sclerosis; Small Intestinal Bacterial Overgrowth

Keywords

Systemic Sclerosis; Small Intestinal Bacterial Overgrowth; Saccaromyces boulardii

Outcome Measures

Primary Outcomes (1)

• Small intestinal Bacterial Overgrowth (Presence or absence)

  Small intestinal Bacterial Overgrowth will be measured by a breath test using a hydrogen monitor. Hydrogen is part of the bacteria metabolism and can be detected in breath. it can be quantified in parts per million. We wil consider presence of Small intestinal Bacterial Overgrowth if a measure \> 10 part per million is obtained in our patients. We will compare the presence or abscense of Small intestinal bacterial overgrowth after the intervention.

  baseline, second month

Secondary Outcomes (1)

• Intensity of gastrointestinal symptoms

  baseline, second month

Study Arms (3)

Saccaromyces boulardii oral tablet

ACTIVE COMPARATOR

Saccharomyces boulardii Oral Tablet 200 mg b.i.d. during 2 weeks, followed by a 2-week rest period and then again 200 mg b.i.d. during 2 consecutive months.

Drug: Saccharomyces Boulardii Oral Tablet

Metronidazole plus S. boulardii

ACTIVE COMPARATOR

Metronidazole 500 mg b.i.d during 1 week, followed by a 3-week rest period and then again 500 mg b.i.d during 2 consecutive months.

Drug: Saccharomyces Boulardii Oral Tablet; Drug: Metronidazole

Metronidazole

ACTIVE COMPARATOR

Metronidazole 500 mg b.i.d during 1 week, plus Saccharomyces boulardii 200 mg b.i.d. during 1 week, follow for only Saccharomyces 200 mg b.i.d. for one another week, 2-week rest period and then this regimen is repeated for two consecutive months.

Drug: Metronidazole

Interventions

Saccharomyces Boulardii Oral Tablet DRUG

Saccharomyces boulardii 200 mg b.i.d. during 2 weeks, followed by a 2-week rest period and then again 200 mg b.i.d. during 2 consecutive months.

Also known as: Saccaromyces boulardii

Metronidazole plus S. boulardii; Saccaromyces boulardii oral tablet

Metronidazole DRUG

Metronidazole 500 mg b.i.d during 1 week, followed by a 3-week rest period and then again 500 mg b.i.d during 2 consecutive months

Also known as: Metronidazole alone

Metronidazole; Metronidazole plus S. boulardii

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Social security beneficiaries affiliated to the "LA RAZA" UMAE HECMN
• Adults over 18 years old
• Male or female subjects
• Diagnosed with scleroderma (2013 ACR-EULAR)
• Score above the 25th percentile in NIH-PROMIS questionnaire
• Positive result (\> 10 ppm) in the hydrogen breath test
• Normal leukocyte and lymphocyte profiles
• Patients who accept to participate in the study by signing the informed consent form

You may not qualify if:

• Gastrointestinal diseases already diagnosed and not associated to systemic sclerosis
• Comorbidities associated to visceral diseases (diabetes, amyloidosis or other infiltrative diseases)
• Currently under biological treatment (or history of biological treatment in the last year) with cyclophosphamide and \> 10 mg prednisone or equivalent
• Allergy or contra-indications to metronidazole or to Saccharomyces boulardii,
• Central venous catheter carriers

Sponsors & Collaborators

• Coordinación de Investigación en Salud, Mexico: lead

Study Sites (1)

Maria del Pilar Cruz Dominguez

Mexico City, Mexico City, 07800, Mexico

Location

Related Publications (1)

• Garcia-Collinot G, Madrigal-Santillan EO, Martinez-Bencomo MA, Carranza-Muleiro RA, Jara LJ, Vera-Lastra O, Montes-Cortes DH, Medina G, Cruz-Dominguez MP. Effectiveness of Saccharomyces boulardii and Metronidazole for Small Intestinal Bacterial Overgrowth in Systemic Sclerosis. Dig Dis Sci. 2020 Apr;65(4):1134-1143. doi: 10.1007/s10620-019-05830-0. Epub 2019 Sep 23.

  PMID: 31549334 DERIVED

MeSH Terms

Conditions

Scleroderma, Systemic

Interventions

Metronidazole

Condition Hierarchy (Ancestors)

Connective Tissue Diseases; Skin and Connective Tissue Diseases; Skin Diseases

Intervention Hierarchy (Ancestors)

Nitroimidazoles; Nitro Compounds; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Maria Pilar Cruz-Domínguez, PhD

  Instituto Mexicano del Seguro Social

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER GOV
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Chief of Researh Division

Model Details: Open Clinical Trial

Study Record Dates

• First Submitted: December 20, 2016
• First Posted: October 2, 2018
• Study Start: June 1, 2015
• Primary Completion: July 26, 2019
• Study Completion: July 26, 2019
• Last Updated: July 30, 2019

Record last verified: 2019-07

Data Sharing

• IPD Sharing: Will not share

Locations

ME (1)