The Effect of Probiotics in HIV-1 Infection (ProGut)

The recruitment status of this study is unknown because the information has not been verified recently.
Verified December 2011 by Oslo University Hospital.
Recruitment status was  Recruiting
Sponsor:
Collaborators:
Karolinska University Hospital
TINE SA
Information provided by (Responsible Party):
MariusTrøseid, Oslo University Hospital
ClinicalTrials.gov Identifier:
NCT01439841
First received: September 16, 2011
Last updated: December 7, 2011
Last verified: December 2011

September 16, 2011
December 7, 2011
October 2011
June 2012   (final data collection date for primary outcome measure)
  • Safety [ Time Frame: 2 months ] [ Designated as safety issue: Yes ]
    Adverse events monitoring during the study period of 2 months
  • Changes in measures of microbial translocation [ Time Frame: 2 months ] [ Designated as safety issue: No ]
    Changes in plasma leves of lipopolysaccharide (LPS) and soluble CD14 from baseline to 2 months (end of study)
  • Changes in markers of immune activation [ Time Frame: 2 months ] [ Designated as safety issue: No ]
    Changes in CD38, HLA-DR and PD-1 on CD8+ and CD4+ T cells from baseline to 2 months (end of study)
Same as current
Complete list of historical versions of study NCT01439841 on ClinicalTrials.gov Archive Site
  • Disease progression in untreated patients [ Time Frame: 2 months ] [ Designated as safety issue: Yes ]
    Changes in CD4 count, viral load, clinical events and indication for ART from baseline to 2 months (end of study)
  • Immune reconstitution in ART treated patients [ Time Frame: 2 months ] [ Designated as safety issue: Yes ]
    Changes in CD4 count from baseline to 2 months (end of study)
  • Gut microbiota composition [ Time Frame: 2 months ] [ Designated as safety issue: No ]
    Changes in gut microbiota (454 pyrosequencing of fecal samples) from baseline to 2 months (end of study)
Same as current
Not Provided
Not Provided
 
The Effect of Probiotics in HIV-1 Infection
The Effect of Probiotics on Microbial Translocation and Immune Activation in HIV-1 Infection. A Randomised Placebo-controlled Trial

HIV progression is closely associated with chronic immune activation driven by leakage of bacterial products from a damaged gut, the investigators largest immunological organ. Notably, the degree of immune activation has been suggested to be a better predictor of disease progression than plasma viral load, and markers of immune activation and gut damage have been identified as therapeutic targets per se. The major damage by HIV to the immune system is an initial massacre of gut mucosal CD4+ Th17 cells. Interestingly, a normal gut flora has been shown to induce the maturation of Th17 cells in the small intestine mucosa. Preliminary reports have shown that the gut flora is altered in HIV-1 infection compared to controls. In this project, the investigators will characterize microbial composition of gut flora in chronic HIV infection with ultradeep sequencing. Gut flora composition will be related to clinical data as well as quantitative data of circulating microbial products and activation markers. Second, in a randomized clinical trial (RCT) the effect of probiotic lactobacilli on HIV pathogenesis and progression will be tested. This Gram-positive strain is clinically tested and is able to colonize the gut.

Objectives:

To explore (i) the safety and tolerability, and (ii) the efficacy of probiotics on HIV-associated microbial translocation, systemic immune activation, disease progression and composition of gut microbiota in chronic HIV-1 infection.

Methodology/Study design:

Approximately 50 patients without current indication for antiretroviral treatment (ART) and 50 patients receiving ART without normalised CD4 counts will be included. A controlled clinical trial will be carried out within each stratum randomised in a 2:1:1 fashion to double blinded intervention and placebo arms as well as an open, untreated control arm, respectively.

Interventional
Phase 2
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
HIV-1 Infection
  • Dietary Supplement: Multi-strain probiotic
    The product consists of Lactobacillus rhamnosus GG, Lactobacillus acidophilus La-5 and Bifidobacterium animalis subsp. lactis Bb-12 added to fermented skimmed milk
    Other Name: Brand name Biola®
  • Dietary Supplement: Placebo
    Fermented and subsequently heat-treated, sterile skimmed milk
  • Other: Control
    No intervention
  • Experimental: Probiotics
    A multi-strain Probiotic consisting of Lactobacillus rhamnosus GG, Lactobacillus acidophilus La-5 and Bifidobacterium animalis subsp. lactis Bb-12 added to fermented skimmed milk (Biola®, TINE SA, Oslo), 250 mL/day for 8 weeks.
    Intervention: Dietary Supplement: Multi-strain probiotic
  • Placebo Comparator: Placebo
    Fermented and subsequently heat-treated, sterile skimmed milk (TINE SA) as active placebo.
    Intervention: Dietary Supplement: Placebo
  • No Intervention: Control
    Control group not receiving intervention.
    Intervention: Other: Control
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
100
December 2012
June 2012   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • For patients without ART: Confirmed diagnosis of HIV infection > 6 months and CD4+ T cell count < 900
  • For patients on stable, effective ART: HIV RNA < 50 copies/ml > 6 months and CD4+ T cell count > 500
  • Signed informed consent.

Exclusion Criteria:

  • Severe illness requiring hospitalization
  • Systemic antibiotics or probiotics the last two months
  • Current immune modulating therapy
  • Infectious diarrhea
  • Inflammatory bowel disease
  • Acute primary HIV infection
  • Patients immigrating from Africa, Asia or Latin-America within the last 6 months.
Both
18 Years and older
No
Contact: Marius Trøseid, MD, PhD +4792440240 marius.troseid@medisin.uio.no
Contact: Dag Kvale, MD, PhD +4795200709 dag.kvale@medisin.uio.no
Norway,   Sweden
 
NCT01439841
ProGut1.0
No
MariusTrøseid, Oslo University Hospital
Oslo University Hospital
  • Karolinska University Hospital
  • TINE SA
Study Director: Geir Gokstad, MD, PhD Oslo University Hospital
Principal Investigator: Marius Trøseid, MD, PhD Oslo University Hospital
Oslo University Hospital
December 2011

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP