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

This study has been completed.
Sponsor:
Collaborator:
Yakult Honsha Co., LTD
Information provided by (Responsible Party):
Esper Georges Kallás, University of Sao Paulo General Hospital
ClinicalTrials.gov Identifier:
NCT02146027
First received: February 18, 2014
Last updated: May 3, 2017
Last verified: May 2017
  Purpose

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.


Condition Intervention Phase
HIV Dietary Supplement: Fermented Milk Drink Yakult 40 Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Supportive Care
Official Title: Immunological Effects of Continuous, Once a Day Use of Lactobacillus Casei Shirota on HIV-infected Patients on Suppressive Antiretroviral Treatment With Poor CD4+ T-cell Recovery

Resource links provided by NLM:


Further study details as provided by Esper Georges Kallás, University of Sao Paulo General Hospital:

Primary Outcome Measures:
  • Increase between baseline and after 6 weeks and 12 weeks in the absolute CD4+ T-cell count in active and placebo group. [ Time Frame: 12 weeks ]
    Only differences greater than 50 T CD4+ cells/mm³ would be included in the analysis.


Secondary Outcome Measures:
  • Change from baseline in level of cell activation at week 12 count [ Time Frame: baseline, 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 level of cell activation at week 6 [ Time Frame: baseline, 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 NK cytototoxic activity against K562 cells at week 6 [ Time Frame: baseline, 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 12 [ Time Frame: baseline, 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

  • Change from baseline in Intestinal symptoms score of the Inflammatory Bowel Disease Questionnaire (IBQD) at week 12 [ Time Frame: baseline, week 12 ]
  • Change from baseline in the intestinal microbiome in the participants taking Lactobacillus casei Shirota at week 12 [ Time Frame: baseline, week 12 ]
  • Number of participants with adverse events reasonable causal relationship with the study product in active and placebo groups [ Time Frame: 12 weeks ]
  • Change from baseline in plasma sCD4 levels at week 6 [ Time Frame: baseline, week 6 ]
    CD14 levels will be measured using commercially available kits

  • Change from baseline in plasma sCD4 levels at week 12 [ Time Frame: baseline, week 12 ]

Estimated Enrollment: 48
Study Start Date: January 2015
Study Completion Date: December 2016
Primary Completion Date: December 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Fermented Milk Drink Yakult 40

Lactobacillus 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.

Dietary Supplement: Fermented Milk Drink Yakult 40
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.
Other Names:
  • Yakult
  • Live Lactic Bacteria (Lactobacillus casei Shirota)
Dietary Supplement: Fermented Milk Drink Yakult 40
Ingredients: Skimmed milk and/or Reconstituted Skimmed Milk, Sugar, Glucose, Live Lactic Bacteria (Lactobacillus casei Shirota) 40 billions per 80 g - concentration of 5 x 108 CFU/g), Flavour. Gluten Free.
Other Names:
  • Live Lactic Bacteria (Lactobacillus casei Shirota)
  • Yakult
Placebo Comparator: Placebo

The 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

Dietary Supplement: Fermented Milk Drink Yakult 40
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.
Other Names:
  • Yakult
  • Live Lactic Bacteria (Lactobacillus casei Shirota)
Dietary Supplement: Fermented Milk Drink Yakult 40
Ingredients: Skimmed milk and/or Reconstituted Skimmed Milk, Sugar, Glucose, Live Lactic Bacteria (Lactobacillus casei Shirota) 40 billions per 80 g - concentration of 5 x 108 CFU/g), Flavour. Gluten Free.
Other Names:
  • Live Lactic Bacteria (Lactobacillus casei Shirota)
  • Yakult

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.

  Eligibility

Ages Eligible for Study:   18 Years to 60 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.
  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: NCT02146027

Locations
Brazil
University of Sao Paulo - General Hospital
São Paulo, Brazil, 01246-903
Sponsors and Collaborators
University of Sao Paulo General Hospital
Yakult Honsha Co., LTD
Investigators
Principal Investigator: Esper G Kallás, MD PhD University of Sao Paulo General Hospital
  More Information

Publications:

Responsible Party: Esper Georges Kallás, MD PhD, University of Sao Paulo General Hospital
ClinicalTrials.gov Identifier: NCT02146027     History of Changes
Other Study ID Numbers: YAKULT
Study First Received: February 18, 2014
Last Updated: May 3, 2017

Keywords provided by Esper Georges Kallás, University of Sao Paulo General Hospital:
HIV
Lactobacillus casei Shirota
NK cell
CD4
Lymphocyte
Cell activation
Antiretroviral therapy
Immune discordants

ClinicalTrials.gov processed this record on August 18, 2017