Clinical trial NCT01838915: Randomized Placebo-controlled Pilot Trial of Prebiotics+Glutamine in HIV Infection
Official title: Gut Microbiota, Bacterial Translocation, Immune Activation and Endothelial Dysfunction in HIV Infection
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: HIV
Keywords: HIV
immunoactivation
bacterial translocation
prebiotics
glutamine
microbiota
Lead sponsor: Fundacion para la Investigacion Biomedica del Hospital Universitario Ramon y Cajal
Sponsor class: OTHER
First posted: 2013-04-24
Enrollment: 45
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Safety
timeFrame: 6 weeks
measure: Changes in markers of bacterial translocation
timeFrame: 6 weeks
measure: Changes in markers of immunoactivation
timeFrame: 6 weeks
measure: Changes in inflammatory markers
timeFrame: 6 weeks
measure: Changes in markers of endothelial dysfunction
timeFrame: 6 weeks
measure: Changes in gut microbiota composition
timeFrame: 6 weeks
Secondary outcomes:
measure: Changes in gut microbiota
timeFrame: 6 weeks
measure: Disease progression in HIV-infected patients.
timeFrame: 6 weeks
measure: Thymic function
timeFrame: 6 weeks
measure: Gene expression in peripheral blood monocytic cells.
timeFrame: 6 weeks
Other outcomes:
Locations:
city: Madrid
country: Spain
facility: Hospital Ramón y Cajal and Hospital Clínico San Carlos
Study officials:
References: