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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Sergio Serrano-Villar, Fundacion para la Investigacion Biomedica del Hospital Universitario Ramon y Cajal
ClinicalTrials.gov Identifier:
NCT01838915
First received: April 22, 2013
Last updated: August 2, 2013
Last verified: August 2013
  Purpose

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.


Condition Intervention Phase
HIV
Dietary Supplement: Prebiotics+Glutamine
Dietary Supplement: Placebo
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
Official Title: Gut Microbiota, Bacterial Translocation, Immune Activation and Endothelial Dysfunction in HIV Infection

Resource links provided by NLM:


Further study details as provided by Fundacion para la Investigacion Biomedica del Hospital Universitario Ramon y Cajal:

Primary Outcome Measures:
  • Safety [ Time Frame: 6 weeks ] [ Designated as safety issue: Yes ]
    Adverse events monitoring during the intervention

  • Changes in markers of bacterial translocation [ Time Frame: 6 weeks ] [ Designated as safety issue: No ]
    Soluble CD14 and increasing permeability binding protein.

  • Changes in markers of immunoactivation [ Time Frame: 6 weeks ] [ Designated as safety issue: No ]
    Changes in percentages of CD4+ and CD8+ T-cells expressing CD25, HLADR, CD38.

  • Changes in inflammatory markers [ Time Frame: 6 weeks ] [ Designated as safety issue: No ]
    Changes in interleukine-6 and high-sensitivity C Reactive Protein

  • Changes in markers of endothelial dysfunction [ Time Frame: 6 weeks ] [ Designated as safety issue: No ]
    Changes in asymmetric dimethylarginine and flow-mediated dilation

  • Changes in gut microbiota composition [ Time Frame: 6 weeks ] [ Designated as safety issue: Yes ]
    Changes in gut microbiota as determined by 454 pyrosequencing.


Secondary Outcome Measures:
  • Changes in gut microbiota [ Time Frame: 6 weeks ] [ Designated as safety issue: No ]
    Changes in gut microbiota by 454 pyrosequencing of fecal samples.

  • Disease progression in HIV-infected patients. [ Time Frame: 6 weeks ] [ Designated as safety issue: Yes ]
    Levels of CD4+ T-cell and HIV-1 RNA copies/mL

  • Thymic function [ Time Frame: 6 weeks ] [ Designated as safety issue: No ]
  • Gene expression in peripheral blood monocytic cells. [ Time Frame: 6 weeks ] [ Designated as safety issue: No ]

Enrollment: 45
Study Start Date: June 2011
Study Completion Date: August 2013
Primary Completion Date: August 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Dietary Supplement: Prebiotics+Glutamine 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 Comparator: Placebo Dietary Supplement: Placebo
Maltodextrin, 20 g.

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

Ages Eligible for Study:   18 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01838915

Locations
Spain
Hospital Ramón y Cajal and Hospital Clínico San Carlos
Madrid, Spain, 28034
Sponsors and Collaborators
Fundacion para la Investigacion Biomedica del Hospital Universitario Ramon y Cajal
  More Information

No publications provided

Responsible Party: Sergio Serrano-Villar, Post-Doctoral Researcher, Fundacion para la Investigacion Biomedica del Hospital Universitario Ramon y Cajal
ClinicalTrials.gov Identifier: NCT01838915     History of Changes
Other Study ID Numbers: 11/284
Study First Received: April 22, 2013
Last Updated: August 2, 2013
Health Authority: Spain: Ethics Committee

Keywords provided by Fundacion para la Investigacion Biomedica del Hospital Universitario Ramon y Cajal:
HIV
immunoactivation
bacterial translocation
prebiotics
glutamine
microbiota

Additional relevant MeSH terms:
HIV Infections
Acquired Immunodeficiency Syndrome
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Slow Virus Diseases

ClinicalTrials.gov processed this record on October 16, 2014