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Randomized Placebo-controlled Pilot Trial of Prebiotics+Glutamine in HIV Infection

Phase 1
Completed
Conditions
HIV
Interventions
Dietary Supplement: Prebiotics+Glutamine
Dietary Supplement: Placebo
Registration Number
NCT01838915
Lead Sponsor
Fundacion para la Investigacion Biomedica del Hospital Universitario Ramon y Cajal
Brief Summary

A rapid and almost complete loss of CD4+ T cells from the gut associated lymphoid tissue (GALT) occurs early in HIV infection, with a permanent damage in the intestinal barrier, changes in gut microbiota, increased bacterial translocation and persistent immune activation, changes that are not restored after the initiation of antiretroviral therapy. The investigators hypothesize than an intervention targetting the enterocyte barrier and the gut microbiota might modify the gastrointestinal tract towards a bifidogenic microbiota and improve markers of bacterial translocation, inflammation, immune activation and endothelial dysfunction.

Detailed Description

This is a randomized placebo-controlled clinical trial to evaluate the safety and effectiveness to modify gut microbiota, bacterial translocation, immune activation and markers of endothelial dysfunction of a dietary supplement (prebiotics + glutamine) during a period of six weeks. The study will enroll four cohorts: 1) HIV-infected, treatment naive individuals; 2) HIV-infected subjects, currently on ART, with \>350 CD4+ T-cells/uL; 3) HIV-infected subjects, currently on ART, with \<350 CD4+ T-cells/uL; 4) HIV negative healthy controls.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
45
Inclusion Criteria
  • After receiving information on the design and objectives of the study, the possible risks involved, and the fact that they can refuse to collaborate at any time, patients will give their informed consent to participate in the study and agree to provide material for the cellular and molecular studies.
  • Aged over 18 years.
  • Group 1: HIV+, Not receiving ART and no previous exposure to ART, at least 2 years since HIV diagnosis.
  • Group 2: HIV+, currently receiving ART for more than 2 years, HIV-1 RNA levels less than 40 copies/ml and more than 350 CD4+ T-cells/uL.
  • Group 3: HIV+, currently receiving ART for more than 2 years, HIV-1 RNA levels less than 40 copies/ml and less than 350 CD4+ T-cells/uL.
  • Group 4: HIV-, healthy controls.
Exclusion Criteria
  • Major cardiovascular risk factors.
  • Concomitant acute diseases.
  • Gastrointestinal disorders.
  • Pregnancy.
  • Antibiotic exposure in the previous month.
  • Regular use of foods or supplements containing prebiotics or probiotics within the 2 weeks prior to initiation of the study.

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Dietary Supplement: Prebiotics+GlutaminePrebiotics+Glutamine-
PlaceboPlacebo-
Primary Outcome Measures
NameTimeMethod
Safety6 weeks

Adverse events monitoring during the intervention

Changes in inflammatory markers6 weeks

Changes in interleukine-6 and high-sensitivity C Reactive Protein

Changes in markers of immunoactivation6 weeks

Changes in percentages of CD4+ and CD8+ T-cells expressing CD25, HLADR, CD38.

Changes in markers of endothelial dysfunction6 weeks

Changes in asymmetric dimethylarginine and flow-mediated dilation

Changes in gut microbiota composition6 weeks

Changes in gut microbiota as determined by 454 pyrosequencing.

Changes in markers of bacterial translocation6 weeks

Soluble CD14 and increasing permeability binding protein.

Secondary Outcome Measures
NameTimeMethod
Disease progression in HIV-infected patients.6 weeks

Levels of CD4+ T-cell and HIV-1 RNA copies/mL

Changes in gut microbiota6 weeks

Changes in gut microbiota by 454 pyrosequencing of fecal samples.

Thymic function6 weeks
Gene expression in peripheral blood monocytic cells.6 weeks

Trial Locations

Locations (1)

Hospital Ramón y Cajal and Hospital Clínico San Carlos

🇪🇸

Madrid, Spain

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