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

HIV Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02146027
• Other study ID #: YAKULT
• Status: Completed
• Phase: Phase 2
• First received: February 18, 2014
• Last updated: May 3, 2017
• Start date: January 2015
• Est. completion date: December 2016

Study information

• Verified date: May 2017
• Source: University of Sao Paulo General Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 48
• Est. completion date: December 2016
• Est. primary completion date: December 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 60 Years

Eligibility

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.

Related Conditions & MeSH terms

• HIV

Intervention

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.
• 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.

Locations

Country	Name	City	State
Brazil	University of Sao Paulo - General Hospital	São Paulo

Sponsors (2)

Lead Sponsor	Collaborator
University of Sao Paulo General Hospital	Yakult Honsha Co., LTD

Country where clinical trial is conducted

Brazil, 

References & Publications (14)

Boyle RJ, Robins-Browne RM, Tang ML. Probiotic use in clinical practice: what are the risks? Am J Clin Nutr. 2006 Jun;83(6):1256-64; quiz 1446-7. Review. — View Citation

Brenchley JM, Douek DC. HIV infection and the gastrointestinal immune system. Mucosal Immunol. 2008 Jan;1(1):23-30. doi: 10.1038/mi.2007.1. Review. — View Citation

Corazza GR, Ginaldi L, Furia N, Marani-Toro G, Di Giammartino D, Quaglino D. The impact of HIV infection on lactose absorptive capacity. J Infect. 1997 Jul;35(1):31-5. — View Citation

Fujimori S, Gudis K, Mitsui K, Seo T, Yonezawa M, Tanaka S, Tatsuguchi A, Sakamoto C. A randomized controlled trial on the efficacy of synbiotic versus probiotic or prebiotic treatment to improve the quality of life in patients with ulcerative colitis. Nu — View Citation

Hummelen R, Vos AP, van't Land B, van Norren K, Reid G. Altered host-microbe interaction in HIV: a target for intervention with pro- and prebiotics. Int Rev Immunol. 2010 Oct;29(5):485-513. doi: 10.3109/08830185.2010.505310. Review. — View Citation

Irvine SL, Hummelen R, Hekmat S, Looman CW, Habbema JD, Reid G. Probiotic yogurt consumption is associated with an increase of CD4 count among people living with HIV/AIDS. J Clin Gastroenterol. 2010 Oct;44(9):e201-5. doi: 10.1097/MCG.0b013e3181d8fba8. — View Citation

Marchetti G, Bellistrì GM, Borghi E, Tincati C, Ferramosca S, La Francesca M, Morace G, Gori A, Monforte AD. Microbial translocation is associated with sustained failure in CD4+ T-cell reconstitution in HIV-infected patients on long-term highly active ant — View Citation

Marchetti G, Cozzi-Lepri A, Merlini E, Bellistrì GM, Castagna A, Galli M, Verucchi G, Antinori A, Costantini A, Giacometti A, di Caro A, D'arminio Monforte A; ICONA Foundation Study Group.. Microbial translocation predicts disease progression of HIV-infec — View Citation

Massanella M, Negredo E, Pérez-Alvarez N, Puig J, Ruiz-Hernández R, Bofill M, Clotet B, Blanco J. CD4 T-cell hyperactivation and susceptibility to cell death determine poor CD4 T-cell recovery during suppressive HAART. AIDS. 2010 Apr 24;24(7):959-68. doi: — View Citation

Piketty C, Castiel P, Belec L, Batisse D, Si Mohamed A, Gilquin J, Gonzalez-Canali G, Jayle D, Karmochkine M, Weiss L, Aboulker JP, Kazatchkine MD. Discrepant responses to triple combination antiretroviral therapy in advanced HIV disease. AIDS. 1998 May 7 — View Citation

Rajasuriar R, Booth D, Solomon A, Chua K, Spelman T, Gouillou M, Schlub TE, Davenport M, Crowe S, Elliott J, Hoy J, Fairley C, Stewart G, Cameron P, Lewin SR. Biological determinants of immune reconstitution in HIV-infected patients receiving antiretrovir — View Citation

Tinmouth J, Kandel G, Tomlinson G, Walmsley S, Steinhart AH, Glazier R. The effect of dairy product ingestion on human immunodeficiency virus-related diarrhea in a sample of predominantly gay men: a randomized, controlled, double-blind, crossover trial. A — View Citation

Trois L, Cardoso EM, Miura E. Use of probiotics in HIV-infected children: a randomized double-blind controlled study. J Trop Pediatr. 2008 Feb;54(1):19-24. Epub 2007 Sep 17. — View Citation

Woelk CH, Beliakova-Bethell N, Goicoechea M, Zhao Y, Du P, Rought SE, Lozach J, Pérez-Santiago J, Richman DD, Smith DM, Little SJ. Gene expression before HAART initiation predicts HIV-infected individuals at risk of poor CD4+ T-cell recovery. AIDS. 2010 J — View Citation

* Note: There are 14 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Increase between baseline and after 6 weeks and 12 weeks in the absolute CD4+ T-cell count in active and placebo group.	Only differences greater than 50 T CD4+ cells/mm³ would be included in the analysis.	12 weeks
Secondary	Change from baseline in level of cell activation at week 12 count	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+	baseline, week 12
Secondary	Change from baseline in level of cell activation at 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+	baseline, week 6
Secondary	Change from baseline in NK cytototoxic activity against K562 cells at 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	baseline, week 6
Secondary	Change from baseline in NK cytototoxic activity against K562 cells at 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	baseline, week 12
Secondary	Change from baseline in Intestinal symptoms score of the Inflammatory Bowel Disease Questionnaire (IBQD) at week 12		baseline, week 12
Secondary	Change from baseline in the intestinal microbiome in the participants taking Lactobacillus casei Shirota at week 12		baseline, week 12
Secondary	Number of participants with adverse events reasonable causal relationship with the study product in active and placebo groups		12 weeks
Secondary	Change from baseline in plasma sCD4 levels at week 6	CD14 levels will be measured using commercially available kits	baseline, week 6
Secondary	Change from baseline in plasma sCD4 levels at week 12		baseline, week 12