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

HIV Clinical Trial

— MicroVIH  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01838915
• Other study ID #: 11/284
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: January 10, 2017
• Est. completion date: June 2018

Study information

• Verified date: February 2019
• Source: Fundacion para la Investigacion Biomedica del Hospital Universitario Ramon y Cajal
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 45
• Est. completion date: June 2018
• Est. primary completion date: June 2018
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

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.

Related Conditions & MeSH terms

• Acquired Immunodeficiency Syndrome
• HIV
• HIV Infections

Intervention

Dietary Supplement:
• Prebiotics+Glutamine
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.
• Placebo
Maltodextrin, 20 g.

Locations

Country	Name	City	State
Spain	Hospital Ramón y Cajal and Hospital Clínico San Carlos	Madrid

Sponsors (1)

Lead Sponsor	Collaborator
Fundacion para la Investigacion Biomedica del Hospital Universitario Ramon y Cajal

Country where clinical trial is conducted

Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Safety	Adverse events monitoring during the intervention	6 weeks
Primary	Changes in markers of bacterial translocation	Soluble CD14 and increasing permeability binding protein.	6 weeks
Primary	Changes in markers of immunoactivation	Changes in percentages of CD4+ and CD8+ T-cells expressing CD25, HLADR, CD38.	6 weeks
Primary	Changes in inflammatory markers	Changes in interleukine-6 and high-sensitivity C Reactive Protein	6 weeks
Primary	Changes in markers of endothelial dysfunction	Changes in asymmetric dimethylarginine and flow-mediated dilation	6 weeks
Primary	Changes in gut microbiota composition	Changes in gut microbiota as determined by 454 pyrosequencing.	6 weeks
Secondary	Changes in gut microbiota	Changes in gut microbiota by 454 pyrosequencing of fecal samples.	6 weeks
Secondary	Disease progression in HIV-infected patients.	Levels of CD4+ T-cell and HIV-1 RNA copies/mL	6 weeks
Secondary	Thymic function		6 weeks
Secondary	Gene expression in peripheral blood monocytic cells.		6 weeks