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Once a Day Use of Lactobacillus Casei Shirota on HIV-infected Patients Infected Patients

Phase 2
Completed
Conditions
HIV
Interventions
Dietary Supplement: Fermented Milk Drink Yakult 40
Registration Number
NCT02146027
Lead Sponsor
University of Sao Paulo General Hospital
Brief Summary

In this study, HIV-infected patients with poor recovery of CD4+ T cells and successful viral control after treatment with antiretroviral therapy will be enrolled to receive once a day Lactobcillus casei Shirota or placebo in a double-blind, randomized fashion. Immune parameters will be monitored for 12 weeks in both arms.

The main outcome is CD4+ T cell recovery. Secondary outcomes will include NK cells and T cells immune parameters.

Detailed Description

In this study, HIV-infected patients with poor recovery of CD4+ T cells and successful viral control after treatment with antiretroviral therapy will be enrolled to receive once a day Lactobcillus casei Shirota or placebo in a double-blind, randomized fashion.

The main objective is to investigate whether the continuous, once a day, 12-weeks use of Yakult product containing Lactobacillus casei Shirota could affect immunological parameters in HIV-infected patients on suppressive antiretroviral treatment with poor CD4+ T cell recovery. A total of 48 volunteers will be followed for 12 week after initiation of daily use of Lactobcillus casei Shirota or placebo, randomized in a 1:1 ratio.

We hypothesize that use of the Yakult product containing Lactobacillus casei Shirota after 12 weeks of continuous use will increase the level of CD4+ T-cells, at least, 50 cells/mm³.

We also propose to investigate several markers of immune response, including T cellular activation and NK cells function, and changes in the intestinal microbiota.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
48
Inclusion Criteria
  • Male or female HIV-1 infected patients aged between 18 and 60 years.
  • Patient on suppressive antiretroviral treatment with poor CD4+ T-cell recovery.
  • No change in antiretroviral therapy in the last six months or intended change in the next 12 weeks.
  • Availability for the study procedures during the study period.
  • Giving informed consent to participate in the study
Exclusion Criteria
  • Diagnosis of any concomitant infections or diseases that might affect immunity or natural history of HIV-1 infection including active Hepatitis B infection, Hepatitis C infection, diabetes mellitus, neoplasias and autoimmune diseases.
  • Use of treatments that might affect immunity in the last four weeks including immunomodulators, corticosteroids (only systemic use for two weeks or more), or antineoplasic agents.
  • History of intolerance or allergy to cow milk or any other component of the study product including lactose intolerance, casein allergy, etc.
  • Pregnancy, nursing mother or intention of became pregnant during the study period (only female participants).
  • Unable to safely store the study product at home in the conditions recommended by the manufacturer.
  • Any other condition that might interfere with the study procedure according to the investigators.

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Fermented Milk Drink Yakult 40Fermented Milk Drink Yakult 40Lactobacillus casei Shirota, contained in the Fermented Milk Drink Yakult 40 Once daily Lactobacillus casei Shirota, with 40 billion bacteria per 80 g (concentration of 5 x 10\^8 CFU/g). Intervention will be used for 12 weeks.
PlaceboFermented Milk Drink Yakult 40The placebo would be an analogous product without Live Lactic Bacteria (Lactobacillus casei Shirota) presented in the same bottle and similar flavor. Both, Yakult 40 and placebo should be stored refrigerated between 1° and 10°C and
Primary Outcome Measures
NameTimeMethod
Increase between baseline and after 6 weeks and 12 weeks in the absolute CD4+ T-cell count in active and placebo group.12 weeks

Only differences greater than 50 T CD4+ cells/mm³ would be included in the analysis.

Secondary Outcome Measures
NameTimeMethod
Change from baseline in level of cell activation at week 6baseline, week 6

Cell activation will be accessed by flow cytometry assays in a FACSCanto flow cytometer, using the following monoclonal antibodies: CD3, CD4, CD8, CD38, CCR5, CD69, anti-HLA-DR+

Change from baseline in Intestinal symptoms score of the Inflammatory Bowel Disease Questionnaire (IBQD) at week 12baseline, week 12
Change from baseline in the intestinal microbiome in the participants taking Lactobacillus casei Shirota at week 12baseline, week 12
Change from baseline in level of cell activation at week 12 countbaseline, week 12

Cell activation will be accessed by flow cytometry assays in a FACSCanto flow cytometer, using the following monoclonal antibodies: CD3, CD4, CD8, CD38, CCR5, CD69, anti-HLA-DR+

Change from baseline in NK cytototoxic activity against K562 cells at week 6baseline, week 6

NK cell phenotyping and function will be assessed according to Long et al., were subpopulations of NK cells will be assessed by the expression of CD56, CD16 molecules in the CD3-CD14-CD20- population of mononuclear cells. Production of IFNgama and CD103a proteins will be evaluated by flow cytometry in K562 stimulated mononuclear cells

Change from baseline in NK cytototoxic activity against K562 cells at week 12baseline, week 12

NK cell phenotyping and function will be assessed according to Long et al., were subpopulations of NK cells will be assessed by the expression of CD56, CD16 molecules in the CD3-CD14-CD20- population of mononuclear cells. Production of IFNgama and CD103a proteins will be evaluated by flow cytometry in K562 stimulated mononuclear cells

Number of participants with adverse events reasonable causal relationship with the study product in active and placebo groups12 weeks
Change from baseline in plasma sCD4 levels at week 6baseline, week 6

CD14 levels will be measured using commercially available kits

Change from baseline in plasma sCD4 levels at week 12baseline, week 12

Trial Locations

Locations (1)

University of Sao Paulo - General Hospital

🇧🇷

São Paulo, Brazil

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