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

Study Overview
=================
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.

Official Title
-----------------
Gut Microbiota, Bacterial Translocation, Immune Activation and Endothelial Dysfunction in HIV Infection

Conditions
-----------------
HIV

Intervention / Treatment
-----------------
* Dietary Supplement: Prebiotics+Glutamine
* Dietary Supplement: Placebo


Participation Criteria
=================
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.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Dietary Supplement: Prebiotics+Glutamine<br> | Dietary Supplement: Prebiotics+Glutamine<br>* Prebiotics are nondigestible food ingredients, generally oligosaccharides, that modify intestinal microbiota balance by stimulating the growth of beneficial bacteria. Glutamine is a non-essential amino acid that can be metabolized by epithelial cells, enhancing barrier function.<br>|
| Placebo Comparator: Placebo<br> | Dietary Supplement: Placebo<br>* Maltodextrin, 20 g.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety | Adverse events monitoring during the intervention | 6 weeks | 
| Changes in markers of bacterial translocation | Soluble CD14 and increasing permeability binding protein. | 6 weeks | 
| Changes in markers of immunoactivation | Changes in percentages of CD4+ and CD8+ T-cells expressing CD25, HLADR, CD38. | 6 weeks | 
| Changes in inflammatory markers | Changes in interleukine-6 and high-sensitivity C Reactive Protein | 6 weeks | 
| Changes in markers of endothelial dysfunction | Changes in asymmetric dimethylarginine and flow-mediated dilation | 6 weeks | 
| Changes in gut microbiota composition | Changes in gut microbiota as determined by 454 pyrosequencing. | 6 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in gut microbiota | Changes in gut microbiota by 454 pyrosequencing of fecal samples. | 6 weeks | 
| Disease progression in HIV-infected patients. | Levels of CD4+ T-cell and HIV-1 RNA copies/mL | 6 weeks | 
| Thymic function |  | 6 weeks | 
| Gene expression in peripheral blood monocytic cells. |  | 6 weeks | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
HIV, immunoactivation, bacterial translocation, prebiotics, glutamine, microbiota