The Effect of Probiotics in HIV-1 Infection (ProGut)
- Full Text View
- Tabular View
- No Study Results Posted
- Disclaimer
- How to Read a Study Record
Purpose
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.
| Condition | Intervention | Phase |
|---|---|---|
|
HIV-1 Infection |
Dietary Supplement: Multi-strain probiotic Dietary Supplement: Placebo Other: Control |
Phase 2 |
| Study Type: | Interventional |
| Study Design: | Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Caregiver, Investigator) Primary Purpose: Treatment |
| Official Title: | The Effect of Probiotics on Microbial Translocation and Immune Activation in HIV-1 Infection. A Randomised Placebo-controlled Trial |
- 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)
- 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)
| Estimated Enrollment: | 100 |
| Study Start Date: | October 2011 |
| Estimated Study Completion Date: | December 2012 |
| Estimated Primary Completion Date: | June 2012 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
|
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.
|
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®
|
|
Placebo Comparator: Placebo
Fermented and subsequently heat-treated, sterile skimmed milk (TINE SA) as active placebo.
|
Dietary Supplement: Placebo
Fermented and subsequently heat-treated, sterile skimmed milk
|
|
No Intervention: Control
Control group not receiving intervention.
|
Other: Control
No intervention
|
Detailed 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.
Eligibility| Ages Eligible for Study: | 18 Years and older |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
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.
Contacts and Locations| Contact: Marius Trøseid, MD, PhD | +4792440240 | marius.troseid@medisin.uio.no |
| Contact: Dag Kvale, MD, PhD | +4795200709 | dag.kvale@medisin.uio.no |
| Norway | |
| Oslo University Hospital | Recruiting |
| Oslo, Norway, 0407 | |
| Contact: Marius Troseid, MD, PhD +4792440240 marius.troseid@medisin.uio.no | |
| Contact: Dag Kvale, MD, PhD +4795200709 dag.kvale@medisin.uio.no | |
| Sub-Investigator: Dag Kvale, MD, PhD | |
| Principal Investigator: Marius Trøseid, MD, PhD | |
| Sweden | |
| Karolinska University Hospital Huddinge | Not yet recruiting |
| Stockholm, Sweden, 14186 | |
| Contact: Anders Sonnerborg, MD, PhD +46736996240 anders.sonnerborg@ki.se | |
| Principal Investigator: Anders Sonnerborg, MD, PhD | |
| Study Director: | Geir Gokstad, MD, PhD | Oslo University Hospital |
| Principal Investigator: | Marius Trøseid, MD, PhD | Oslo University Hospital |
More Information
No publications provided
| Responsible Party: | MariusTrøseid, Marius Trøseid, MD, PhD, Oslo University Hospital |
| ClinicalTrials.gov Identifier: | NCT01439841 History of Changes |
| Other Study ID Numbers: | ProGut1.0 |
| Study First Received: | September 16, 2011 |
| Last Updated: | December 7, 2011 |
| Health Authority: | Norway: Directorate of Health Norway: Regional Ethics Commitee |
Keywords provided by Oslo University Hospital:
|
HIV microbial translocation immune activation probiotics |
Additional relevant MeSH terms:
|
HIV Infections Lentivirus Infections Retroviridae Infections RNA Virus Infections Virus Diseases |
Sexually Transmitted Diseases, Viral Sexually Transmitted Diseases Immunologic Deficiency Syndromes Immune System Diseases |
ClinicalTrials.gov processed this record on May 22, 2013