Treatment With Probiotics (Saccharomyces Boulardii) and Its Role in Bacterial Translocation and Immune Reconstitution in VIH Infection.

Objectives: MAIN: To evaluate the parameters of microbial translocation after treatment with probiotics (Saccharomyces boulardii) in HIV+ patients and its role on immune reconstitution and the changes in gut microbiota composition.

SECONDARY OBJECTIVES: 1) To analyze the progress of immune activity markers after the administration of probiotics. 2) To determine the improvement of CD4+ lymphocytes and HIV viral load in patients after taking probiotics.

Methods: Design: A prospective randomized open controlled double-blinded trial, to be performed at a tertiary care hospital in Barcelona. Subjects: Chronic HIV infected patients. Sample size: 44 cases. They´ll be divided in 2 groups: (1) Patients with CD4 +> 400 cells / ml and undetectable viral load for more than two years (22 cases) and (2) Patients with immunodiscordancy, defined as patients with CD4 + T cells lower than 350 cells / ml despite 4-7 years of effective antiretroviral therapy. (22 cases). Intervention: Patients were randomized in 2 subgroups: (A) they´ll receive daily oral supplementation with S. boulardii for 3 months and (B) they ´ll receive placebo. Variables: bacterial lipopolisaccharide levels measured by the Lipid-Binding protein (LBP), parameters of immune activation in plasma (soluble CD14, IFN-Υ, TNF-Alpha, IL (interleukine)-2, IL-5, IL-6, IL-12)and gut microbiota composition prior to the use of probiotics (baseline), at 3 and 6 months. Immunological and clinical data. Outcome measures: quantification of bacterial translocation levels, markers of activity and immune recovery. Analysis: Comparison of variables before and after the intervention. The analysis will be performed by biological and immunological effectiveness.

Study Overview

• Status: Unknown
• Conditions: HIV -1 Infection
• Intervention / Treatment: Dietary supplement: Placebo; Dietary supplement: Probiotic.

• Study Type: Interventional
• Enrollment (Actual): 44
• Phase: Phase 2

Contacts and Locations

Study Locations

• Spain
  • Barcelona, Spain, 08003
    • Hospital del Mar

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients with chronic HIV infection and viral load undetectable > two years with stable ART CD4> 400 cells / ml.
• Patients with chronic HIV infection and viral load undetectable> two years with stable ART CD4 <350 cells / ml.
• Inform consent signed.
• Aged between 18- No limit.

Exclusion Criteria:

• Patients who receive or have received in the past 6 months food supplements containing probiotics.
• Patients who have received antibiotic treatment in the last two months
• Patients who are poor presupposes adherence to dietary supplements.
• Patients who have changed the TAR in the last three months.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Probiotic; A probiotic (Saccharomyces boulardii) 2 caps/ 8h for 12 weeks.	Dietary supplement: Probiotic.
Placebo Comparator: Placebo; No active substance is given.	Dietary supplement: Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To evaluate microbial translocation-Binding lipopolysaccharide Protein (LBP).		From randomisation to 6 months.
To evaluate Gut microbiota composition.	Change in gut microbiota (454 pyrosequencing of fecal samples).	From randomisation to 6 months.

Secondary Outcome Measures

Outcome Measure	Time Frame
To evaluate Markers of immune activity: soluble CD14 (sCD14), interferon gamma (IFN-Υ), tumor necrosis factor (TNF), IL-6, Reactive C protein, D -dimer, fibrinogen.	From randomisation to 6 months.
Analyse parameters that determine the immune status: CD4 + lymphocyte count, CD 8 + and HIV viral load.	From randomisation to 6 months.

Collaborators and Investigators

• Sponsor: Parc de Salut Mar

Publications and helpful links

General Publications

• Villar-Garcia J, Hernandez JJ, Guerri-Fernandez R, Gonzalez A, Lerma E, Guelar A, Saenz D, Sorli L, Montero M, Horcajada JP, Knobel Freud H. Effect of probiotics (Saccharomyces boulardii) on microbial translocation and inflammation in HIV-treated patients: a double-blind, randomized, placebo-controlled trial. J Acquir Immune Defic Syndr. 2015 Mar 1;68(3):256-63. doi: 10.1097/QAI.0000000000000468.

Study record dates

Study Major Dates

• Study Start: August 1, 2012
• Primary Completion (Actual): July 1, 2013
• Study Completion (Anticipated): March 1, 2017

Study Registration Dates

• First Submitted: July 22, 2013
• First Submitted That Met QC Criteria: July 24, 2013
• First Posted (Estimate): July 25, 2013

Study Record Updates

• Last Update Posted (Estimate): November 15, 2016
• Last Update Submitted That Met QC Criteria: November 11, 2016
• Last Verified: November 1, 2016

More Information

Terms related to this study

• Keywords: HIV; inflammation; Probiotic; Microbial translocation; microbiota composition
• Additional Relevant MeSH Terms: Pathologic Processes; Disease Attributes; Infections; Communicable Diseases
• Other Study ID Numbers: PROB-VIH