HIV-1 InfectionProGutNCT01439841
The Effect of Probiotics in HIV-1 Infection
A study testing Multi-strain probiotic in people with HIV-1 Infection, run by Oslo University Hospital at 2 sites in 2 countries.
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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- HIV-1 Infection
- What is being tested?
- Multi-strain probiotic
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 32 participants
- Where
- 2 sitesin 2 countries
- Study dates
- Oct 2011to Jun 2013
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
Trial locations and contacts
2 sites in 2 countries.
2 sites in 2 countries
About this study
Official title: 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.
Read the 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.
- Conditions
- HIV-1 Infection
- Being tested
- Multi-strain probiotic, Placebo
- Keywords
- HIV, microbial translocation, immune activation, probiotics
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Multi-strain probioticDietary supplement
Also called Brand name Biola®
The product consists of Lactobacillus rhamnosus GG, Lactobacillus acidophilus La-5 and Bifidobacterium animalis subsp. lactis Bb-12 added to fermented skimmed milk
PlaceboDietary supplement
Fermented and subsequently heat-treated, sterile skimmed milk
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Dietary Supplement: Multi-strain probiotic |
| Placebo | Placebo comparator | Fermented and subsequently heat-treated, sterile skimmed milk (TINE SA) as active placebo. Receives: Dietary Supplement: Placebo |
| Control | No intervention | No intervention |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety
Adverse events monitoring during the study period of 2 months
Measured: 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)
Measured: 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)
Measured: 2 months
Secondary outcomes (3)
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)
Measured: 2 months
Immune reconstitution in ART treated patients
Changes in CD4 count from baseline to 2 months (end of study)
Measured: 2 months
Gut microbiota composition
Changes in gut microbiota (454 pyrosequencing of fecal samples) from baseline to 2 months (end of study)
Measured: 2 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Sep 2011 (estimated)
- Study startOct 2011
- Primary completionApr 2013
- Study completionJun 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for HIV-1 InfectionStudies of the same condition, open and under way.
- More trials run by Oslo University HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 32 participants (actual)
Sponsor and investigators
- Lead sponsor
- Oslo University Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Karolinska University Hospital, Tine
- Responsible party
- Principal investigator, MariusTrøseid, Oslo University Hospital
- Investigators
- Geir Gokstad, MD, PhD, Study director, Oslo University HospitalMarius Trøseid, MD, PhD, Principal investigator, Oslo University Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01439841
- Sponsor's protocol ID
- ProGut1.0
- Acronym
- ProGut
- Status last verified
- Sep 2017
- First submitted
- 16 Sep 2011
- Last updated
- 28 Sep 2017
- Results posted
- No
- Data monitoring committee
- No
Publications
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.
PubMed 26258571
Study at a glance
From the registry record, last updated by the sponsor on 28 Sep 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Effect of Probiotics on Microbial Translocation and Immune Activation in HIV-1 Infection. A Randomised Placebo-controlled Trial
- ClinicalTrials.gov ID
- NCT01439841
- Acronym / sponsor ID
- ProGut / ProGut1.0
- Conditions
- HIV-1 Infection
- Keywords
- HIV, microbial translocation, immune activation, probiotics
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 32 participants (actual)
- Lead sponsor
- Oslo University HospitalUniversity, hospital or other
- Collaborators
- Karolinska University Hospital, Tine
- Study start
- Oct 2011
- Primary completion
- Apr 2013 (actual)
- Study completion
- Jun 2013 (actual)
- First posted
- 23 Sep 2011 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Probiotics | Experimental | Dietary Supplement: Multi-strain probioticA 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. |
| Placebo | Placebo comparator | Dietary Supplement: PlaceboFermented and subsequently heat-treated, sterile skimmed milk (TINE SA) as active placebo. |
| Control | No intervention | –No intervention |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- 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.
Key exclusion criteria (7 listed)
- Severe illness requiring hospitalization
- Systemic antibiotics or probiotics the last two months
- Current immune modulating therapy
- Infectious diarrhea
- Inflammatory bowel disease
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Multi-strain probioticAlso: Brand name Biola®The product consists of Lactobacillus rhamnosus GG, Lactobacillus acidophilus La-5 and Bifidobacterium animalis subsp. lactis Bb-12 added to fermented skimmed milk | Dietary supplement | Probiotics |
| PlaceboFermented and subsequently heat-treated, sterile skimmed milk | Dietary supplement | Placebo |
Primary outcome
Safety
Time frame: 2 months
Adverse events monitoring during the study period of 2 months
Changes in measures of microbial translocation
Time frame: 2 months
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
Changes in CD38, HLA-DR and PD-1 on CD8+ and CD4+ T cells from baseline to 2 months (end of study)
3 secondary outcomes
Disease progression in untreated patients
Time frame: 2 months
Immune reconstitution in ART treated patients
Time frame: 2 months
Gut microbiota composition
Time frame: 2 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Sep 2017.
- Derived from this study: PubMed 26258571Stiksrud 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Geir Gokstad, MD, PhD study director
Oslo University Hospital
Marius Trøseid, MD, PhD principal investigator
Oslo University Hospital
2 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Multi-strain probiotic in people with HIV-1 Infection, run by Oslo University Hospital at 2 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 28 Sep 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Norway, Sweden. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Safety (time frame: 2 months). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01439841, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Sep 2017.