NCT02146027

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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
48

participants targeted

Target at P25-P50 for phase_2 hiv

Timeline
Completed

Started Jan 2015

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

February 18, 2014

Completed
3 months until next milestone

First Posted

Study publicly available on registry

May 23, 2014

Completed
7 months until next milestone

Study Start

First participant enrolled

January 1, 2015

Completed
1.9 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

December 1, 2016

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

December 1, 2016

Completed
Last Updated

May 4, 2017

Status Verified

May 1, 2017

Enrollment Period

1.9 years

First QC Date

February 18, 2014

Last Update Submit

May 3, 2017

Conditions

HIV

Keywords

HIVLactobacillus casei ShirotaNK cellCD4LymphocyteCell activationAntiretroviral therapyImmune discordants

Outcome Measures

Primary Outcomes (1)

  • 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 Outcomes (9)

  • Change from baseline in level of cell activation at week 12 count

    baseline, week 12

  • Change from baseline in level of cell activation at week 6

    baseline, week 6

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

    baseline, week 6

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

    baseline, week 12

  • Change from baseline in Intestinal symptoms score of the Inflammatory Bowel Disease Questionnaire (IBQD) at week 12

    baseline, week 12

  • +4 more secondary outcomes

Study Arms (2)

Fermented Milk Drink Yakult 40

EXPERIMENTAL

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

Placebo

PLACEBO COMPARATOR

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

Interventions

Fermented Milk Drink Yakult 40DIETARY_SUPPLEMENT

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.

Also known as: Yakult, Live Lactic Bacteria (Lactobacillus casei Shirota)
Fermented Milk Drink Yakult 40Placebo

Eligibility Criteria

Age18 Years - 60 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64)

You may qualify if:

  • 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

You may not qualify if:

  • 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.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

University of Sao Paulo - General Hospital

São Paulo, 01246-903, Brazil

Location

Related 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. doi: 10.1093/ajcn/83.6.1256.

    PMID: 16762934RESULT

  • 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.

    PMID: 19079157RESULT

  • 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. doi: 10.1016/s0163-4453(97)90905-1.

    PMID: 9279721RESULT

  • 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. Nutrition. 2009 May;25(5):520-5. doi: 10.1016/j.nut.2008.11.017. Epub 2009 Feb 8.

    PMID: 19201576RESULT

  • 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.

    PMID: 20839912RESULT

  • 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.

    PMID: 20463586RESULT

  • Marchetti G, Bellistri 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 antiretroviral therapy. AIDS. 2008 Oct 1;22(15):2035-8. doi: 10.1097/QAD.0b013e3283112d29.

    PMID: 18784466RESULT

  • Marchetti G, Cozzi-Lepri A, Merlini E, Bellistri 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-infected antiretroviral-naive patients with high CD4+ cell count. AIDS. 2011 Jul 17;25(11):1385-94. doi: 10.1097/QAD.0b013e3283471d10.

    PMID: 21505312RESULT

  • Massanella M, Negredo E, Perez-Alvarez N, Puig J, Ruiz-Hernandez 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: 10.1097/QAD.0b013e328337b957.

    PMID: 20177358RESULT

  • 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;12(7):745-50. doi: 10.1097/00002030-199807000-00011.

    PMID: 9619806RESULT

  • 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 antiretroviral therapy: the role of interleukin 7 and interleukin 7 receptor alpha and microbial translocation. J Infect Dis. 2010 Oct 15;202(8):1254-64. doi: 10.1086/656369.

    PMID: 20812848RESULT

  • 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. doi: 10.1093/tropej/fmm066. Epub 2007 Sep 17.

    PMID: 17878180RESULT

  • 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. Arch Intern Med. 2006 Jun 12;166(11):1178-83. doi: 10.1001/archinte.166.11.1178.

    PMID: 16772244RESULT

  • Woelk CH, Beliakova-Bethell N, Goicoechea M, Zhao Y, Du P, Rought SE, Lozach J, Perez-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 Jan 16;24(2):217-22. doi: 10.1097/QAD.0b013e328334f1f0.

    PMID: 19952713RESULT

Study Officials

  • Esper G Kallás, MD PhD

    University of Sao Paulo General Hospital

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 2
Allocation
RANDOMIZED
Masking
TRIPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR
Purpose
SUPPORTIVE CARE
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
MD PhD

Study Record Dates

First Submitted

February 18, 2014

First Posted

May 23, 2014

Study Start

January 1, 2015

Primary Completion

December 1, 2016

Study Completion

December 1, 2016

Last Updated

May 4, 2017

Record last verified: 2017-05

Locations

BR(1)