The Effect of Probiotics in HIV-1 Infection

HIV-1 Infection Clinical Trial

— ProGut  

Official title:

The Effect of Probiotics on Microbial Translocation and Immune Activation in HIV-1 Infection. A Randomised Placebo-controlled Trial

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01439841
• Other study ID #: ProGut1.0
• Status: Completed
• Phase: N/A
• First received: September 16, 2011
• Last updated: September 26, 2017
• Start date: October 2011
• Est. completion date: June 2013

Study information

• Verified date: September 2017
• Source: Oslo University Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Description:

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 32
• Est. completion date: June 2013
• Est. primary completion date: April 2013
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Communicable Diseases
• HIV Infections
• HIV-1 Infection
• Infection

Intervention

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
• Placebo
Fermented and subsequently heat-treated, sterile skimmed milk

Locations

Country	Name	City	State
Norway	Oslo University Hospital	Oslo
Sweden	Karolinska University Hospital Huddinge	Stockholm

Sponsors (3)

Lead Sponsor	Collaborator
Oslo University Hospital	Karolinska University Hospital, Tine

Countries where clinical trial is conducted

Norway,  Sweden, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Safety	Adverse events monitoring during the study period of 2 months	2 months
Primary	Changes in measures of microbial translocation	Changes in plasma leves of lipopolysaccharide (LPS) and soluble CD14 from baseline to 2 months (end of study)	2 months
Primary	Changes in markers of immune activation	Changes in CD38, HLA-DR and PD-1 on CD8+ and CD4+ T cells from baseline to 2 months (end of study)	2 months
Secondary	Disease progression in untreated patients	Changes in CD4 count, viral load, clinical events and indication for ART from baseline to 2 months (end of study)	2 months
Secondary	Immune reconstitution in ART treated patients	Changes in CD4 count from baseline to 2 months (end of study)	2 months
Secondary	Gut microbiota composition	Changes in gut microbiota (454 pyrosequencing of fecal samples) from baseline to 2 months (end of study)	2 months