The Effect of Probiotics in HIV-1 Infection

NCT01439841 | Completed

• 1 other identifier: ProGut1.0
• Study Type: interventional
• Target: 32
• Locations: 2 countries
• Sites: 2

Brief 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.

Conditions

HIV-1 Infection

Keywords

HIV; microbial translocation; immune activation; probiotics

Outcome Measures

Primary Outcomes (3)

• Safety

  Adverse events monitoring during the study period of 2 months

  2 months

• 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

• 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 Outcomes (3)

• Disease progression in untreated patients

  2 months

• Immune reconstitution in ART treated patients

  2 months

• Gut microbiota composition

  2 months

Study Arms (3)

Probiotics

EXPERIMENTAL

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.

Dietary Supplement: Multi-strain probiotic

Placebo

PLACEBO COMPARATOR

Fermented and subsequently heat-treated, sterile skimmed milk (TINE SA) as active placebo.

Dietary Supplement: Placebo

Control

NO INTERVENTION

No intervention

Interventions

Multi-strain probiotic DIETARY_SUPPLEMENT

The product consists of Lactobacillus rhamnosus GG, Lactobacillus acidophilus La-5 and Bifidobacterium animalis subsp. lactis Bb-12 added to fermented skimmed milk

Also known as: Brand name Biola®

Probiotics

Placebo DIETARY_SUPPLEMENT

Fermented and subsequently heat-treated, sterile skimmed milk

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Oslo University Hospital: lead
• Karolinska University Hospital: collaborator
• Tine: collaborator

Study Sites (2)

Oslo University Hospital

Oslo, 0407, Norway

Location

Karolinska University Hospital Huddinge

Stockholm, 14186, Sweden

Location

Related Publications (1)

• Stiksrud B, Nowak P, Nwosu FC, Kvale D, Thalme A, Sonnerborg A, Ueland PM, Holm K, Birkeland SE, Dahm AE, Sandset PM, Rudi K, Hov JR, Dyrhol-Riise AM, Troseid M. Reduced Levels of D-dimer and Changes in Gut Microbiota Composition After Probiotic Intervention in HIV-Infected Individuals on Stable ART. J Acquir Immune Defic Syndr. 2015 Dec 1;70(4):329-37. doi: 10.1097/QAI.0000000000000784.

  PMID: 26258571 DERIVED

Study Officials

• Geir Gokstad, MD, PhD

  Oslo University Hospital

  STUDY DIRECTOR

• Marius Trøseid, MD, PhD

  Oslo University Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Marius Trøseid, MD, PhD

Study Record Dates

• First Submitted: September 16, 2011
• First Posted: September 23, 2011
• Study Start: October 1, 2011
• Primary Completion: April 1, 2013
• Study Completion: June 1, 2013
• Last Updated: September 28, 2017

Record last verified: 2017-09

Locations

SE (1); NO (1)