HIV-1 InfectionPhase 2NCT02706717
Effects of the Probiotic Visbiome Extra Strength on Gut Microbiome & Immune Activation Markers
A Phase 2 study testing Visbiome Extra Strength in people with HIV-1 Infection, run by Advancing Clinical Therapeutics Globally for HIV/AIDS and Other Infections at 25 sites in 2 countries.
Trial summary
The purpose of the study was to evaluate whether the probiotic Visbiome Extra Strength reduces inflammation in HIV-infected men and women when compared to a placebo (inactive medication like a dummy pill). 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?
- Visbiome Extra Strength
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 93 participants
- Where
- 25 sitesin 2 countries
- Study dates
- Apr 2016to 28 Aug 2017
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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
- HIV-1 infection, documented by any licensed rapid HIV test or HIV enzyme or chemiluminescence immunoassay (E/CIA) test kit at any time prior to study entry and confirmed by a licensed Western blot or a second antibody test by a method other than the initial rapid HIV and/or E/CIA, or by HIV-1 antigen, plasma HIV-1 RNA viral load.
- NOTE: The term "licensed" refers to a US FDA-approved kit.
- WHO (World Health Organization) and CDC (Centers for Disease Control and Prevention) guidelines mandate that confirmation of the initial test result must use a test that is different from the one used for the initial assessment. A reactive initial rapid test should be confirmed by either another type of rapid assay or an E/CIA that is based on a different antigen preparation and/or different test principle (eg, indirect versus competitive), or a Western blot or a plasma HIV-1 RNA viral load.
- Currently on continuous antiretroviral therapy (ART) for ≥48 weeks prior to study entry with no change in the ART regimen within the 24 weeks prior to study entry except as noted below.
- NOTE A: Continuous ART is defined as continuous ART for the 48-week period prior to study entry with no ART interruption longer than 7 consecutive days.
- NOTE B: Modifications of ART during the 24 weeks prior to study entry are permitted in certain circumstances. For example, the change in formulation (eg, from standard formulation to fixed-dose combination including ART modifications switching from ritonavir- to cobicistat-boosted protease inhibitors or from tenofovir disoproxil fumarate to tenofovir alafenamide) is allowed within 24 weeks prior to study entry. A within-class, single-drug substitution (eg, switch from nevirapine to efavirenz or from atazanavir to darunavir) is allowed within 24 weeks prior to study entry, with the exception of a switch between any other NRTI to/from abacavir. No other changes in ART within the 24 weeks prior to study entry are permitted.
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- No plan to change ART regimen for the study duration.
- Screening CD4+ cell count >200 cells/mm3 obtained within 45 days prior to study entry by any US laboratory that has a CLIA certification or its equivalent.
- Screening HIV-1 RNA levels <50 copies/mL using a FDA-approved assay performed by any laboratory that has a CLIA certification or its equivalent within 45 days prior to study entry.
- HIV-1 RNA levels below the limit of quantification using a FDA-approved assay with a quantification limit of 50 copies/mL or lower for at least 48 weeks prior to study entry performed by any laboratory that has a CLIA certification or its equivalent.
- NOTE: Single determinations that are between the assay quantification limit and 500 copies/mL (ie, "blips") are allowed as long as the preceding and subsequent determinations are below the level of quantification. The screening value may serve as the subsequent undetectable value following a blip.
- The following laboratory values obtained within 45 days prior to entry by any US laboratory that has a CLIA certification or its equivalent:
- Absolute neutrophil count (ANC) ≥1000/mm3
- Hemoglobin ≥10.0 g/dL for men and 9.0 g/dL for women
- Platelet count ≥50,000/mm3
- Aspartate aminotransferase (AST) (SGOT) ≤5 x upper limit normal (ULN)
- Alanine aminotransferase (ALT) (SGPT) ≤5 x ULN
- Alkaline phosphatase ≤5 x upper limit normal ULN
- Total bilirubin ≤2.5 x ULN (if on atazanavir ≤5 x ULN)
- Calculated creatinine clearance (CrCl) >60 mL/min, as estimated by the Cockcroft-Gault equation.
- For females of reproductive potential, negative serum or urine pregnancy test within 45 days prior to entry by any US clinic or laboratory that has a CLIA certification or its equivalent, or is using a point-of-care (POC)/ CLIA-waived test, or at any network-approved non-US laboratory or clinic that operates in accordance with Good Clinical Laboratory Practices (GCLP) and participates in appropriate external quality assurance programs.
- If participating in sexual activity that could lead to pregnancy, the female study participant must be willing to use a contraceptive while receiving protocol-specified medication. At least one of the following methods MUST be used:
- Condoms (male or female), with or without a spermicidal agent
- Diaphragm or cervical cap with spermicide
- Intrauterine device (IUD)
- Hormone-based contraceptive
- Ability and willingness of participant or legal guardian/representative to provide informed consent.
Who cannot join
- Initiation of ART during acute HIV infection.
- NOTE: Participants who initiate ART within 6 months of HIV seroconversion are considered to have been initiated during acute infection and are excluded.
- Receipt of antibiotic therapy within 60 days prior to study entry.
- NOTE: Antibiotics for opportunistic infection prophylaxis are exclusionary.
- Known allergy/sensitivity or any hypersensitivity to components of Visbiome Extra Strength or its formulation.
- Use of investigational therapies or investigational vaccines within 90 days prior to study entry.
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- Non-investigational vaccinations within 2 weeks prior to study entry.
- Active drug or alcohol use or dependence that in the opinion of the site investigator would interfere with adherence to study requirements.
- Serious illness requiring systemic treatment and/or hospitalization within 30 days prior to entry.
- History of positive HCV antibody with detectable HCV RNA in plasma within 48 weeks prior to study entry.
- NOTE: Persons with positive HCV Ab but negative plasma HCV RNA are allowed to participate. Sites must document negative HCV RNA within 24 weeks of study entry.
- History of positive HBsAg within 48 weeks prior to study entry.
- Liver cirrhosis, history of inflammatory bowel disease, total colectomy, colon or rectal anastomosis, bowel resection, or current colostomy.
- Current diagnosis of diabetes.
- Either breastfeeding or pregnant within 24 weeks prior to study entry.
- OIs within 45 days prior to study entry.
- Use of any of the following medications/products for more than 3 consecutive days within the 60 days prior to study entry:
- Immunosuppressives (eg, azathioprine, corticosteroids greater than 20 mg per day [physiologic replacement doses are allowed], cyclosporine, mycophenolate, intravenous immunoglobulin (IVIG), interferon, sirolimus, sulfasalazine, tacrolimus).
- Immune modulators (eg, cytokines [eg, IL-2], granulocyte colony stimulating factor, growth hormone, tumor necrosis factor antagonists, thalidomide).
- Antineoplastic agents (except for topical agents for skin cancer).
- Probiotics and prebiotics (supplements and products).
- NOTE: Yogurt with live cultures is allowed.
- History of lactose intolerance or milk allergy.
- Any episode of acute or persistent diarrhea within 60 days prior to study entry.
- NOTES:
- Diarrhea is defined as three or more stools per day that are liquid/loose/watery and will take the shape of a container. If the duration of loose stools meeting this criterion definition is greater than 30 days, this is chronic diarrhea and is not exclusionary.
- Acute diarrhea is defined as 3-14 day duration.
- Persistent diarrhea is defined as 15-30 day duration.
- Weight loss or gain of more than 25 pounds in the 24 weeks prior to study entry.
Trial locations and contacts
25 sites in 2 countries.
25 sites in 2 countries
United States24 sites
University of Colorado Hospital CRS (6101)
Aurora, Colorado, 80045
Johns Hopkins Adult AIDS CRS (201)
Baltimore, Maryland, 21287
31788 Alabama CRS
Birmingham, Alabama, 35294
Unc Aids Crs (3201)
Chapel Hill, North Carolina, 27514
Northwestern University CRS (2701)
Chicago, Illinois, 60611
Rush University Medical Center (2702)
Chicago, Illinois, 60612
University of Cincinnati CRS (2401)
Cincinnati, Ohio, 45267
Case CRS (2501)
Cleveland, Ohio, 44106
The Ohio State University AIDS CRS (2301)
Columbus, Ohio, 43210
Trinity Health and Wellness Center CRS (31443)
Dallas, Texas, 75208
Greensboro CRS (3203)
Greensboro, North Carolina, 27401
Houston AIDS Research Team CRS (31473)
Houston, Texas, 77030
UCLA CARE Center CRS (601)
Los Angeles, California, 90095
Vanderbilt Therapeutics CRS (3652)
Nashville, Tennessee, 37204
7804 Weill Cornell Chelsea CRS
New York, New York, 10010
Columbia Physicians and Surgeons CRS (30329)
New York, New York, 10032
7803 Weill Cornell Upton CRS
New York, New York, 10065
31786 New Jersey Medical School Clinical Research Center CRS
Newark, New Jersey, 07103
6201 Penn Therapeutics CRS
Philadelphia, Pennsylvania, 19104
Pittsburgh CRS (1001)
Pittsburgh, Pennsylvania, 15213
701 University of California, San Diego AntiViral Research Center CRS
San Diego, California, 92103
801 University of California, San Francisco HIV/AIDS CRS
San Francisco, California, 94110
University of Washington AIDS CRS (1401)
Seattle, Washington, 98104
Washington University CRS (2101)
St Louis, Missouri, 63110
About this study
Official title: Safety, Tolerability, and Effects of the Probiotic Visbiome Extra Strength on Gut Microbiome and Immune Activation Markers in HIV-Infected Participants on Suppressive Antiretroviral Therapy: A Phase II Study
The purpose of the study was to evaluate whether the probiotic Visbiome Extra Strength reduces inflammation in HIV-infected men and women when compared to a placebo (inactive medication like a dummy pill). The study evaluated whether taking Visbiome Extra Strength by mouth for 24 weeks was safe and well-tolerated for HIV-infected persons on antiretroviral therapy (ART). Probiotics are germs such as yeast or bacteria that are found in food and supplements that are used to improve the health of the digestive system. Many people refer to probiotics as "helpful bacteria." These bacteria live in the body and help the body work normally. In some medical conditions, including HIV infection, helpful bacteria are replaced with bacteria that can change the normal intestinal function and increase inflammation. The investigators tested whether giving a probiotic restored normal intestinal function and decreased inflammation.
Read the detailed description
This was a phase II, randomized, double-blind, two-arm study to evaluate whether there is a significant change in sCD14 after 24 weeks of probiotic Visbiome Extra Strength (ES) therapy, and to determine the safety and tolerability of this agent in HIV-infected participants on stable antiretroviral therapy (ART). Participants were randomized 1:1 to Visbiome ES and placebo arms. Both arms initiated study treatment at Week 2 and took 1 sachet per day for the first 2 weeks and then 1 sachet twice daily for the next 22 weeks. All participants were followed for an additional 12 weeks off study product.
The study clinic visits included Entry (Week 0), and Weeks 2, 6, 14, 25, 26, and 38. Plasma for the primary outcome was collected at Weeks 0, 2, 25, and 26. The evaluations of safety (clinical assessment for signs and symptoms, diagnoses, and laboratory tests) were done at Weeks 2, 6, 14, 26, and 38.
Currently, the results are entered for the primary outcome measure and select secondary outcomes only. The results on the remaining secondary outcomes will be posted when they become available.
- Conditions
- HIV-1 Infection
- Being tested
- Visbiome Extra Strength, Placebo
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Visbiome Extra StrengthDrug
From week 2 to 4, participant will receive one sachet orally daily. From week 4 to 26, participant will receive one sachet orally twice daily.
PlaceboDrug
Also called Control
From week 2 to 4, participant will receive one sachet orally daily. From week 4 to 26, participant will receive one sachet orally twice daily.
| Study group | Role | What they receive |
|---|---|---|
| Visbiome Extra Strength | Active comparator | Not described Receives: Drug: Visbiome Extra Strength |
| Placebo for Visbiome Extra Strength | Placebo comparator | Not described Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in sCD14 From Baseline to Week 25/26
Baseline is defined as the average of the Entry and Week 2 values. Week 25/26 is defined as the average of the Week 25 and Week 26 values.
Absolute change was calculated as the value at Week 25/26 minus the value at Baseline.
Measured: Weeks 0, 2, 25, and 26
Secondary outcomes (29)
Change in IL-6 From Week 2 to Week 26
IL-6 data are not available as of June, 2018. These data are based on assays which are to be tested in batch to minimize variability. Due to batch testing, shipment of samples for testing could not begin until after the study follow-up completion, which was 3 months after the primary completion date. Please note that these secondary outcomes were not included in the primary analysis report. There are many outcomes in this study and the labs had to give priority to the assays planned to be included in the primary manuscript.
Measured: Weeks 2 and 26
Change in IP-10 From Week 2 to Week 26
All values were log10 transformed prior to calculating change and conducting analyses.
Absolute change was calculated as the value at Week 26 minus the value at Week 2. Mean changes were exponentiated to be back on the untransformed scale and corresponds to a mean fold change.
Measured: Weeks 2 and 26
Change in sCD163 From Week 2 to Week 26
sCD163 data are not available as of June, 2018. These data are based on assays which are to be tested in batch to minimize variability. Due to batch testing, shipment of samples for testing could not begin until after the study follow-up completion, which was 3 months after the primary completion date. Please note that these secondary outcomes were not included in the primary analysis report. There are many outcomes in this study and the labs had to give priority to the assays planned to be included in the primary manuscript.
Measured: Weeks 2 and 26
Change in sTNF-RI From Week 2 to Week 26
sTNF-RI data are not available as of June, 2018. These data are based on assays which are to be tested in batch to minimize variability. Due to batch testing, shipment of samples for testing could not begin until after the study follow-up completion, which was 3 months after the primary completion date. Please note that these secondary outcomes were not included in the primary analysis report. There are many outcomes in this study and the labs had to give priority to the assays planned to be included in the primary manuscript.
Measured: Weeks 2 and 26
Change in Oxidized LDL From Week 2 to Week 26
Oxidized LDL data are not available as of June, 2018. These data are based on assays which are to be tested in batch to minimize variability. Due to batch testing, shipment of samples for testing could not begin until after the study follow-up completion, which was 3 months after the primary completion date. Please note that these secondary outcomes were not included in the primary analysis report. There are many outcomes in this study and the labs had to give priority to the assays planned to be included in the primary manuscript.
Measured: Weeks 2 and 26
Change in Kynurenine to Tryptophan Ratio From Week 2 to Week 26
Fold change was calculated as the value at Week 26 divided by the value at Week 2.
Measured: Weeks 2 and 26
Change in D-dimer From Week 2 to Week 26
All values were log10 transformed prior to calculating change and conducting analyses.
Absolute change was calculated as the value at Week 26 minus the value at Week 2. Mean changes were exponentiated to be back on the untransformed scale and corresponds to a mean fold change.
Measured: Weeks 2 and 26
Change in LPS From Week 2 to Week 26
LPS data are not available as of June, 2018. These data are based on assays which are to be tested in batch to minimize variability. Due to batch testing, shipment of samples for testing could not begin until after the study follow-up completion, which was 3 months after the primary completion date. Please note that these secondary outcomes were not included in the primary analysis report. There are many outcomes in this study and the labs had to give priority to the assays planned to be included in the primary manuscript.
Measured: Weeks 2 and 26
Change in LBP From Week 2 to Week 26
LBP data are not available as of June, 2018. These data are based on assays which are to be tested in batch to minimize variability. Due to batch testing, shipment of samples for testing could not begin until after the study follow-up completion, which was 3 months after the primary completion date. Please note that these secondary outcomes were not included in the primary analysis report. There are many outcomes in this study and the labs had to give priority to the assays planned to be included in the primary manuscript.
Measured: Weeks 2 and 26
Change in CD4+ Cell Count From Week 2 to Week 26.
Absolute change was calculated as the value at Week 26 minus the value at Week 2.
Measured: Weeks 2 and 26
Change in CD4+/CD8+ Ratio From Week 2 to Week 26.
Fold change was calculated as the value at Week 26 divided by the value at Week 2.
Measured: Weeks 2 and 26
Change in %CD14++CD16- From Week 2 to Week 26.
Absolute change was calculated as the value at Week 26 minus the value at Week 2.
Measured: Weeks 2 and 26
Change in %CD14++CD16+ From Week 2 to Week 26
Absolute change was calculated as the value at Week 26 minus the value at Week 2.
Measured: Weeks 2 and 26
Change in %CD14lowCD16hi From Week 2 to Week 26
%CD14lowCD16hi data are not available as of June, 2018. These data are based on assays which are to be tested in batch to minimize variability. Due to batch testing, shipment of samples for testing could not begin until after the study follow-up completion, which was 3 months after the primary completion date. Please note that these secondary outcomes were not included in the primary analysis report. There are many outcomes in this study and the labs had to give priority to the assays planned to be included in the primary manuscript.
Measured: Weeks 2 and 26
Change in %CD4+CD38+ From Week 2 to Week 26.
%CD4+CD38+ data are not available as of June, 2018. These data are based on assays which are to be tested in batch to minimize variability. Due to batch testing, shipment of samples for testing could not begin until after the study follow-up completion, which was 3 months after the primary completion date. Please note that these secondary outcomes were not included in the primary analysis report. There are many outcomes in this study and the labs had to give priority to the assays planned to be included in the primary manuscript.
Measured: Weeks 2 and 26
Change in %CD4+HLA-DR+ From Week 2 to Week 26.
%CD4+HLA-DR+ data are not available as of June, 2018. These data are based on assays which are to be tested in batch to minimize variability. Due to batch testing, shipment of samples for testing could not begin until after the study follow-up completion, which was 3 months after the primary completion date. Please note that these secondary outcomes were not included in the primary analysis report. There are many outcomes in this study and the labs had to give priority to the assays planned to be included in the primary manuscript.
Measured: Weeks 2 and 26
Change in %CD4+CD38+HLA-DR+ From Week 2 to Week 26.
Absolute change was calculated as the value at Week 26 minus the value at Week 2.
Measured: Weeks 2 and 26
Change in %CD8+CD38+ From Week 2 to Week 26.
%CD8+CD38+ data are not available as of June, 2018. These data are based on assays which are to be tested in batch to minimize variability. Due to batch testing, shipment of samples for testing could not begin until after the study follow-up completion, which was 3 months after the primary completion date. Please note that these secondary outcomes were not included in the primary analysis report. There are many outcomes in this study and the labs had to give priority to the assays planned to be included in the primary manuscript.
Measured: Weeks 2 and 26
Change in %CD8+HLA-DR+ From Week 2 to Week 26.
%CD8+HLA-DR+ data are not available as of June, 2018. These data are based on assays which are to be tested in batch to minimize variability. Due to batch testing, shipment of samples for testing could not begin until after the study follow-up completion, which was 3 months after the primary completion date. Please note that these secondary outcomes were not included in the primary analysis report. There are many outcomes in this study and the labs had to give priority to the assays planned to be included in the primary manuscript.
Measured: Weeks 2 and 26
Change in %CD8+CD38+HLA-DR+ From Week 2 to Week 26.
Absolute change was calculated as the value at Week 26 minus the value at Week 2.
Measured: Weeks 2 and 26
Change in %CD4+CD28-CD57+ From Week 2 to Week 26.
Absolute change was calculated as the value at Week 26 minus the value at Week 2.
Measured: Weeks 2 and 26
Change in %CD8+CD28-CD57+ From Week 2 to Week 26.
Absolute change was calculated as the value at Week 26 minus the value at Week 2.
Measured: Weeks 2 and 26
Change in Chao1 Richness Index From Week 2 to Week 26.
Absolute change was calculated as the value at Week 26 minus the value at Week 2.
Chao1 is a diversity index that reflects how many different quantifiable types (species, individuals, items, etc…) there are in a dataset (see Chao reference). Chao1 diversity is a richness measure which quantifies how many different types there are in a given dataset. The Chao 1 index can range from 1 to infinity as it is constrained only by the number of types defined as measurable. The greater a value is, the more diverse it is but only in direct comparison to groups considering the same parameters. That is, diversity indices are relative to the community (cohort or ecosystem) studied in part due to the definition of the "types" that are considered.
Measured: Weeks 2 and 26
Change in Shannon Diversity Index From Week 2 to Week 26.
Absolute change was calculated as the value at Week 26 minus the value at Week 2.
Shannon is a diversity index that reflects how many different quantifiable types (species, individuals, items, etc…) there are in a dataset (see Lemos and Magurran references). The Shannon index is an estimator of richness and evenness. It quantifies uncertainty (entropy) within a dataset. The Shannon Index ranges from 0-5. The greater a value is, the more diverse it is but only in direct comparison to groups considering the same parameters. That is, diversity indices are relative to the community (cohort or ecosystem) studied in part due to the definition of the "types" that are considered.
Measured: Weeks 2 and 26
Change in Chao1 Richness Index From Week 26 to Week 38.
Absolute change was calculated as the value at Week 38 minus the value at Week 26.
Chao1 is a diversity index that reflects how many different quantifiable types (species, individuals, items, etc…) there are in a dataset (see Chao reference). Chao1 diversity is a richness measure which quantifies how many different types there are in a given dataset. The Chao 1 index can range from 1 to infinity as it is constrained only by the number of types defined as measurable. The greater a value is, the more diverse it is but only in direct comparison to groups considering the same parameters. That is, diversity indices are relative to the community (cohort or ecosystem) studied in part due to the definition of the "types" that are considered.
Measured: Weeks 26 and 38
Change in Shannon Diversity Index From Week 26 to Week 38.
Absolute change was calculated as the value at Week 38 minus the value at Week 26.
Shannon is a diversity index that reflects how many different quantifiable types (species, individuals, items, etc…) there are in a dataset (see Lemos and Magurran references). The Shannon index is an estimator of richness and evenness. It quantifies uncertainty (entropy) within a dataset. The Shannon Index ranges from 0-5. The greater a value is, the more diverse it is but only in direct comparison to groups considering the same parameters. That is, diversity indices are relative to the community (cohort or ecosystem) studied in part due to the definition of the "types" that are considered.
Measured: Weeks 26 and 38
Change in I-FABP From Week 2 to Week 26.
Absolute change was calculated as the value at Week 26 minus the value at Week 2.
Measured: Weeks 2 and 26
Safety
Summary of the highest adverse event grade (0-5) for each participant.
Protocol definition of Adverse Events: 1) signs and symptoms Grade ≥3 and any that led to a change in treatment regardless of grade; 2) new diagnoses; 3) Grade ≥3 lab values and any that led to a change in treatment or were associated with a diagnosis were recorded, regardless of grade.
DAIDS AE Grading Table, Version 2.0 was used.
Measured: Treatment dispensation to Week 38
Tolerability
Tolerability was successfully completing the protocol-defined treatment period.
Measured: Treatment dispensation to Week 38
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Mar 2016 (estimated)
- Study startApr 2016
- Primary completion5 Jun 2017
- Study completion28 Aug 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for HIV-1 InfectionStudies of the same condition, open and under way.
- 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Care provider
- Enrolment
- 93 participants (actual)
Sponsor and investigators
- Lead sponsor
- Advancing Clinical Therapeutics Globally for HIV/AIDS and Other Infections
- Sponsor type
- Research network
- Collaborators
- National Institute of Allergy and Infectious Diseases (NIAID), Exegi Pharma, LLC
- Responsible party
- Sponsor
- Investigators
- Adriana Andrade, MD, MPH, Study chair, Johns Hopkins UniversityEdgar T Overton, MD, Study chair, University of Alabama at Birmingham
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02706717
- Sponsor's protocol ID
- ACTG A5350
- Other IDs
- 1U01AI068636
- Status last verified
- Dec 2019
- First submitted
- 8 Mar 2016
- Last updated
- 6 Jan 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Chao, Anne. Scandinavian Journal of Statistics, 1 January 1984, Vol.11(4), pp.265-270
Lemos LN, Fulthorpe RR, Triplett EW, Roesch LF. Rethinking microbial diversity analysis in the high throughput sequencing era. J Microbiol Methods. 2011 Jul;86(1):42-51. doi: 10.1016/j.mimet.2011.03.014. Epub 2011 Mar 30.
PubMed 21457733Magurran A. 2004. Measuring Biological Diversity. Blackwell Science Ltd, Oxford, United Kingdom
Study at a glance
From the registry record, last updated by the sponsor on 6 Jan 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Safety, Tolerability, and Effects of the Probiotic Visbiome Extra Strength on Gut Microbiome and Immune Activation Markers in HIV-Infected Participants on Suppressive Antiretroviral Therapy: A Phase II Study
- ClinicalTrials.gov ID
- NCT02706717
- Acronym / sponsor ID
- ACTG A5350
- Conditions
- HIV-1 Infection
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 93 participants (actual)
- Lead sponsor
- Advancing Clinical Therapeutics Globally for HIV/AIDS and Other InfectionsResearch network
- Collaborators
- National Institute of Allergy and Infectious Diseases (NIAID), Exegi Pharma, LLC
- Study start
- Apr 2016 (actual)
- Primary completion
- 5 Jun 2017 (actual)
- Study completion
- 28 Aug 2017 (actual)
- First posted
- 11 Mar 2016 (estimated)
- Results
- Posted 27 Jun 2018
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of the study was to evaluate whether the probiotic Visbiome Extra Strength reduces inflammation in HIV-infected men and women when compared to a placebo (inactive medication like a dummy pill). The study evaluated whether taking Visbiome Extra Strength by mouth for 24 weeks was safe and well-tolerated for HIV-infected persons on antiretroviral therapy (ART). Probiotics are germs such as yeast or bacteria that are found in food and supplements that are used to improve the health of the digestive system. Many people refer to probiotics as "helpful bacteria." These bacteria live in the body and help the body work normally. In some medical conditions, including HIV infection, helpful bacteria are replaced with bacteria that can change the normal intestinal function and increase inflammation. The investigators tested whether giving a probiotic restored normal intestinal function and decreased inflammation.
Detailed description
This was a phase II, randomized, double-blind, two-arm study to evaluate whether there is a significant change in sCD14 after 24 weeks of probiotic Visbiome Extra Strength (ES) therapy, and to determine the safety and tolerability of this agent in HIV-infected participants on stable antiretroviral therapy (ART). Participants were randomized 1:1 to Visbiome ES and placebo arms. Both arms initiated study treatment at Week 2 and took 1 sachet per day for the first 2 weeks and then 1 sachet twice daily for the next 22 weeks. All participants were followed for an additional 12 weeks off study product.
The study clinic visits included Entry (Week 0), and Weeks 2, 6, 14, 25, 26, and 38. Plasma for the primary outcome was collected at Weeks 0, 2, 25, and 26. The evaluations of safety (clinical assessment for signs and symptoms, diagnoses, and laboratory tests) were done at Weeks 2, 6, 14, 26, and 38.
Currently, the results are entered for the primary outcome measure and select secondary outcomes only. The results on the remaining secondary outcomes will be posted when they become available.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, care provider)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Visbiome Extra Strength | Active comparator | Drug: Visbiome Extra Strength |
| Placebo for Visbiome Extra Strength | Placebo comparator | Drug: Placebo |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (27 listed)
- HIV-1 infection, documented by any licensed rapid HIV test or HIV enzyme or chemiluminescence immunoassay (E/CIA) test kit at any time prior to study entry and confirmed by a licensed Western blot or a second antibody test by a method other than the initial rapid HIV and/or E/CIA, or by HIV-1 antigen, plasma HIV-1 RNA viral load.
- NOTE: The term "licensed" refers to a US FDA-approved kit.
- WHO (World Health Organization) and CDC (Centers for Disease Control and Prevention) guidelines mandate that confirmation of the initial test result must use a test that is different from the one used for the initial assessment. A reactive initial rapid test should be confirmed by either another type of rapid assay or an E/CIA that is based on a different antigen preparation and/or different test principle (eg, indirect versus competitive), or a Western blot or a plasma HIV-1 RNA viral load.
- Currently on continuous antiretroviral therapy (ART) for ≥48 weeks prior to study entry with no change in the ART regimen within the 24 weeks prior to study entry except as noted below.
- NOTE A: Continuous ART is defined as continuous ART for the 48-week period prior to study entry with no ART interruption longer than 7 consecutive days.
Key exclusion criteria (29 listed)
- Initiation of ART during acute HIV infection.
- NOTE: Participants who initiate ART within 6 months of HIV seroconversion are considered to have been initiated during acute infection and are excluded.
- Receipt of antibiotic therapy within 60 days prior to study entry.
- NOTE: Antibiotics for opportunistic infection prophylaxis are exclusionary.
- Known allergy/sensitivity or any hypersensitivity to components of Visbiome Extra Strength or its formulation.
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 |
|---|---|---|
| Visbiome Extra StrengthFrom week 2 to 4, participant will receive one sachet orally daily. From week 4 to 26, participant will receive one sachet orally twice daily. | Drug | Visbiome Extra Strength |
| PlaceboAlso: ControlFrom week 2 to 4, participant will receive one sachet orally daily. From week 4 to 26, participant will receive one sachet orally twice daily. | Drug | Placebo for Visbiome Extra Strength |
Primary outcome
Change in sCD14 From Baseline to Week 25/26
Time frame: Weeks 0, 2, 25, and 26
Baseline is defined as the average of the Entry and Week 2 values. Week 25/26 is defined as the average of the Week 25 and Week 26 values. Absolute change was calculated as the value at Week 25/26 minus the value at Baseline.
29 secondary outcomes
Change in IL-6 From Week 2 to Week 26
Time frame: Weeks 2 and 26
Change in IP-10 From Week 2 to Week 26
Time frame: Weeks 2 and 26
Change in sCD163 From Week 2 to Week 26
Time frame: Weeks 2 and 26
Change in sTNF-RI From Week 2 to Week 26
Time frame: Weeks 2 and 26
Change in Oxidized LDL From Week 2 to Week 26
Time frame: Weeks 2 and 26
Change in Kynurenine to Tryptophan Ratio From Week 2 to Week 26
Time frame: Weeks 2 and 26
Change in D-dimer From Week 2 to Week 26
Time frame: Weeks 2 and 26
Change in LPS From Week 2 to Week 26
Time frame: Weeks 2 and 26
Change in LBP From Week 2 to Week 26
Time frame: Weeks 2 and 26
Change in CD4+ Cell Count From Week 2 to Week 26.
Time frame: Weeks 2 and 26
Change in CD4+/CD8+ Ratio From Week 2 to Week 26.
Time frame: Weeks 2 and 26
Change in %CD14++CD16- From Week 2 to Week 26.
Time frame: Weeks 2 and 26
Change in %CD14++CD16+ From Week 2 to Week 26
Time frame: Weeks 2 and 26
Change in %CD14lowCD16hi From Week 2 to Week 26
Time frame: Weeks 2 and 26
Change in %CD4+CD38+ From Week 2 to Week 26.
Time frame: Weeks 2 and 26
Change in %CD4+HLA-DR+ From Week 2 to Week 26.
Time frame: Weeks 2 and 26
Change in %CD4+CD38+HLA-DR+ From Week 2 to Week 26.
Time frame: Weeks 2 and 26
Change in %CD8+CD38+ From Week 2 to Week 26.
Time frame: Weeks 2 and 26
Change in %CD8+HLA-DR+ From Week 2 to Week 26.
Time frame: Weeks 2 and 26
Change in %CD8+CD38+HLA-DR+ From Week 2 to Week 26.
Time frame: Weeks 2 and 26
Change in %CD4+CD28-CD57+ From Week 2 to Week 26.
Time frame: Weeks 2 and 26
Change in %CD8+CD28-CD57+ From Week 2 to Week 26.
Time frame: Weeks 2 and 26
Change in Chao1 Richness Index From Week 2 to Week 26.
Time frame: Weeks 2 and 26
Change in Shannon Diversity Index From Week 2 to Week 26.
Time frame: Weeks 2 and 26
Change in Chao1 Richness Index From Week 26 to Week 38.
Time frame: Weeks 26 and 38
Change in Shannon Diversity Index From Week 26 to Week 38.
Time frame: Weeks 26 and 38
Change in I-FABP From Week 2 to Week 26.
Time frame: Weeks 2 and 26
Safety
Time frame: Treatment dispensation to Week 38
Tolerability
Time frame: Treatment dispensation to Week 38
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Jan 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- BackgroundChao, Anne. Scandinavian Journal of Statistics, 1 January 1984, Vol.11(4), pp.265-270
- Background: PubMed 21457733Lemos LN, Fulthorpe RR, Triplett EW, Roesch LF. Rethinking microbial diversity analysis in the high throughput sequencing era. J Microbiol Methods. 2011 Jul;86(1):42-51. doi: 10.1016/j.mimet.2011.03.014. Epub 2011 Mar 30.
- BackgroundMagurran A. 2004. Measuring Biological Diversity. Blackwell Science Ltd, Oxford, United Kingdom
- The Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE Grading Table), Version 1.0, December 2004 (Clarification, August 2009).Link provided by the sponsor.
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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.
Adriana Andrade, MD, MPH study chair
Johns Hopkins University
Edgar T Overton, MD study chair
University of Alabama at Birmingham
25 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Visbiome Extra Strength in people with HIV-1 Infection, run by Advancing Clinical Therapeutics Globally for HIV/AIDS and Other Infections at 25 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 27 inclusion and 29 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 6 Jan 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 25 sites in United States, Puerto Rico. 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.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 27 Jun 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Change in sCD14 From Baseline to Week 25/26 (time frame: Weeks 0, 2, 25, and 26). 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 NCT02706717, which also lists 3 linked publications.
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 6 Jan 2020.