HIV-1 InfectionPhase 2PROOV IT IINCT02441231
Probiotic Visbiome for Inflammation and Translocation in HIV II
A Phase 2 study testing Visbiome in people with HIV-1 Infection, run by University Health Network, Toronto at 2 sites in Canada.
Trial summary
Modern antiretroviral therapy (ART) has transformed the clinical care and lived experience of HIV infection. However, increased rates of adverse health conditions that are related to immune activation, such as cardiovascular disease (CVD) and neurodegenerative disease in ART-treated individuals persist. Read more about this study
- Who is it for?
- Ages 19 years and older, men only
- Conditions the study is for
- HIV-1 Infection
- What is being tested?
- Visbiome
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 36 participants
- Where
- 2 sitesCanada
- Study dates
- Nov 2015to May 2019
- Phase
- Phase 2
- 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 19 years and older
- Men only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Documented HIV-1 infection
- Male adult (age >18 years)
- Currently on ART (>2 years but <10 years)
- Undetectable HIV-1 viral load <50 copies/ml for the past 2 years (1 viral blip below 500 copies/ml permitted in the past year)
- Last CD4 count <350 cells/μl, and >70% over the past 2 years <350 cells/μl
- Ability to provide informed consent
Who cannot join
- Current alcohol or substance use judged by the Investigator to potentially interfere with subject study compliance
- Taking pharmaceutical-grade probiotics
- Any of the following abnormal laboratory results in screening:
- Hemoglobin <85 g/L
- Neutrophil count <750 cells/μl
- Platelet count <50,000 cells/μL
Show all 10Show fewer
- AST or ALT >5X the upper limit of normal
- Colitis
- Liver fibrosis (decompensated cirrhosis), portal hypertension or clinical hepatitis
- Other significant underlying disease (non-HIV-1) that might impinge upon disease progression or death
Trial locations and contacts
2 sites in 1 country.
Canada2 sites, 2 recruiting
- Recruiting
Maple Leaf Medical Clinic
Toronto, Ontario, M5G 1K2
Colin Kovacs, MD, 416-465-3252, ckovacs@mlmedical.com
Colin Kovacs, MD
- Recruiting
Toronto General Hospital, UHN
Toronto, Ontario, M5G 2N2
Sharon Walmsley, MD, 416-340-3871, sharon.walmsley@uhn.ca
Sharon Walmsley, MD
About this study
Official title: Probiotic Visbiome for Inflammation and Translocation in HIV II (PROOV IT II)
Modern antiretroviral therapy (ART) has transformed the clinical care and lived experience of HIV infection. However, increased rates of adverse health conditions that are related to immune activation, such as cardiovascular disease (CVD) and neurodegenerative disease in ART-treated individuals persist. An important cause of this inflammation is the gut CD4 T cell loss and the "leaking" or translocation of luminal gut bacteria and other microbes across the bowel wall and into the bloodstream.
The use of complementary and alternative therapies is very common among people living with HIV, with estimates ranging from 16-60%. However, their efficacy has generally not been well demonstrated. Probiotics are live microbes that may provide a health benefit to the host and the investigators believe that the simultaneous use of probiotics along with ART will improve gut CD4 T cell restoration and function and therefore reduce microbial translocation and immune activation.
A major challenge to HIV treatment is the suboptimal CD4 T cell count despite successful HIV suppression on ART in immunologic non-responders (INRs). These individuals are at increased risk of AIDS-related deaths and non-AIDS related comorbidities that may be associated with increased immune activation and microbial translocation from the gut mucosa. With limited treatment options, alternative therapies to reduce inflammation and restore gut immunology will be important. Probiotic Visbiome consists of a high potency blend of eight different probiotics. The precise mechanism of action of Visbiome is unknown,but preclinical studies have shown that Visbiome may modulate the immune response towards an immunoregualtory phenotype with increased the levels of IL-10 and reduced levels of proinflammatory cytokines (TNFα, IL1β and IL-8). Therefore,the investigators believe that the "beneficial" bacteria from Visbiome will accelerate the normalization of gut immune cells and function in HIV-infected INRs. It is hypothesized consumption of Visbiome for 48 weeks will help restore the immune system in INRs who have suboptimal immune reconstitution to currently available ART. Resolution of gut immune cells will mean that microbial translocation and immune activation will be normalized and will reduce the rates of HIV-associated comorbidities.
- Conditions
- HIV-1 Infection
- Being tested
- Visbiome, Placebo
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
VisbiomeDrug
Visbiome probiotic
PlaceboOther
Placebo
| Study group | Role | What they receive |
|---|---|---|
| Probiotic Group | Experimental | Visbiome probiotic group (900 billion bacteria daily; 2 sachets daily) Receives: Drug: Visbiome |
| Placebo Group | Placebo comparator | Placebo comparator group Receives: Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percent change in blood immune activation
Percent change in blood immune activation (co-expression of CD38 and HLA-DR) on CD8 T cells at week 48 in participants randomized to probiotic Visbiome versus the placebo arm
Measured: 48 weeks
Secondary outcomes (11)
Level of microbial translocation (including LSP and sCD14)
Measured: 48 weeks
Plasma level of inflammation and coagulation (including IL-6, D-dimer and CRP)
Measured: 48 weeks
Number and function of gut immune cells (including CD4 T cell subsets)
Measured: 48 weeks
Intestinal permeability (Lac/Mac ratio)
Measured: 48 weeks
Bacterial community diversity, determined by 16s rRNA gene sequencing of penile swabs
Measured: 48 weeks
Bacterial community composition, determined by 16s rRNA gene sequencing of penile swabs
Measured: 48 weeks
Gut HIV DNA levels
Measured: 48 weeks
Canadian Diet History Questionnaire
Measured: 48 weeks
Safety assessed by AE monitoring and participant questionnaire
Measured: 48 weeks
Tolerability of Visbiome assessed by AE monitoring and participant questionnaire
Measured: 48 weeks
Adherence to Visbiome assessed by participant questionnaire and sachet count
Measured: 48 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 May 2015 (estimated)
- Study startNov 2015
- Primary completionMay 2019 (estimated)
- Study completionMay 2019 (estimated)
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 University Health Network, TorontoThe 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 36 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University Health Network, Toronto
- Sponsor type
- University, hospital or other
- Collaborators
- CIHR Canadian HIV Trials Network
- Responsible party
- Sponsor
- Investigators
- Rupert Kaul, MD, Principal investigator, University Health Network, Toronto
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02441231
- Sponsor's protocol ID
- CTNPT 022B
- Acronym
- PROOV IT II
- Status last verified
- Apr 2018
- First submitted
- 23 Apr 2015
- Last updated
- 18 Apr 2018
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Rousseau RK, Walmsley SL, Lee T, Rosenes R, Reinhard RJ, Malazogu F, Benko E, Huibner S, Kovacs CM, Singer J, Kim CJ, Kaul R. Randomized, Blinded, Placebo-Controlled Trial of De Simone Formulation Probiotic During HIV-Associated Suboptimal CD4+ T Cell Recovery. J Acquir Immune Defic Syndr. 2022 Feb 1;89(2):199-207. doi: 10.1097/QAI.0000000000002840.
PubMed 34693932
Study at a glance
From the registry record, last updated by the sponsor on 18 Apr 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Probiotic Visbiome for Inflammation and Translocation in HIV II (PROOV IT II)
- ClinicalTrials.gov ID
- NCT02441231
- Acronym / sponsor ID
- PROOV IT II / CTNPT 022B
- Conditions
- HIV-1 Infection
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 36 participants (estimated)
- Lead sponsor
- University Health Network, TorontoUniversity, hospital or other
- Collaborators
- CIHR Canadian HIV Trials Network
- Study start
- Nov 2015 (actual)
- Primary completion
- May 2019 (estimated)
- Study completion
- May 2019 (estimated)
- First posted
- 12 May 2015 (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.
Modern antiretroviral therapy (ART) has transformed the clinical care and lived experience of HIV infection. However, increased rates of adverse health conditions that are related to immune activation, such as cardiovascular disease (CVD) and neurodegenerative disease in ART-treated individuals persist. An important cause of this inflammation is the gut CD4 T cell loss and the "leaking" or translocation of luminal gut bacteria and other microbes across the bowel wall and into the bloodstream.
The use of complementary and alternative therapies is very common among people living with HIV, with estimates ranging from 16-60%. However, their efficacy has generally not been well demonstrated. Probiotics are live microbes that may provide a health benefit to the host and the investigators believe that the simultaneous use of probiotics along with ART will improve gut CD4 T cell restoration and function and therefore reduce microbial translocation and immune activation.
A major challenge to HIV treatment is the suboptimal CD4 T cell count despite successful HIV suppression on ART in immunologic non-responders (INRs). These individuals are at increased risk of AIDS-related deaths and non-AIDS related comorbidities that may be associated with increased immune activation and microbial translocation from the gut mucosa. With limited treatment options, alternative therapies to reduce inflammation and restore gut immunology will be important. Probiotic Visbiome consists of a high potency blend of eight different probiotics. The precise mechanism of action of Visbiome is unknown,but preclinical studies have shown that Visbiome may modulate the immune response towards an immunoregualtory phenotype with increased the levels of IL-10 and reduced levels of proinflammatory cytokines (TNFα, IL1β and IL-8). Therefore,the investigators believe that the "beneficial" bacteria from Visbiome will accelerate the normalization of gut immune cells and function in HIV-infected INRs. It is hypothesized consumption of Visbiome for 48 weeks will help restore the immune system in INRs who have suboptimal immune reconstitution to currently available ART. Resolution of gut immune cells will mean that microbial translocation and immune activation will be normalized and will reduce the rates of HIV-associated comorbidities.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Probiotic Group | Experimental | Drug: VisbiomeVisbiome probiotic group (900 billion bacteria daily; 2 sachets daily) |
| Placebo Group | Placebo comparator | Other: PlaceboPlacebo comparator group |
Who may qualify
- Ages
- 19 years and older
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Documented HIV-1 infection
- Male adult (age >18 years)
- Currently on ART (>2 years but <10 years)
- Undetectable HIV-1 viral load <50 copies/ml for the past 2 years (1 viral blip below 500 copies/ml permitted in the past year)
- Last CD4 count <350 cells/μl, and >70% over the past 2 years <350 cells/μl
Key exclusion criteria (10 listed)
- Current alcohol or substance use judged by the Investigator to potentially interfere with subject study compliance
- Taking pharmaceutical-grade probiotics
- Any of the following abnormal laboratory results in screening:
- Colitis
- Liver fibrosis (decompensated cirrhosis), portal hypertension or clinical hepatitis
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 |
|---|---|---|
| VisbiomeVisbiome probiotic | Drug | Probiotic Group |
| PlaceboPlacebo | Other | Placebo Group |
Primary outcome
Percent change in blood immune activation
Time frame: 48 weeks
Percent change in blood immune activation (co-expression of CD38 and HLA-DR) on CD8 T cells at week 48 in participants randomized to probiotic Visbiome versus the placebo arm
11 secondary outcomes
Level of microbial translocation (including LSP and sCD14)
Time frame: 48 weeks
Plasma level of inflammation and coagulation (including IL-6, D-dimer and CRP)
Time frame: 48 weeks
Number and function of gut immune cells (including CD4 T cell subsets)
Time frame: 48 weeks
Intestinal permeability (Lac/Mac ratio)
Time frame: 48 weeks
Bacterial community diversity, determined by 16s rRNA gene sequencing of penile swabs
Time frame: 48 weeks
Bacterial community composition, determined by 16s rRNA gene sequencing of penile swabs
Time frame: 48 weeks
Gut HIV DNA levels
Time frame: 48 weeks
Canadian Diet History Questionnaire
Time frame: 48 weeks
Safety assessed by AE monitoring and participant questionnaire
Time frame: 48 weeks
Tolerability of Visbiome assessed by AE monitoring and participant questionnaire
Time frame: 48 weeks
Adherence to Visbiome assessed by participant questionnaire and sachet count
Time frame: 48 weeks
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Apr 2018.
- Derived from this study: PubMed 34693932Rousseau RK, Walmsley SL, Lee T, Rosenes R, Reinhard RJ, Malazogu F, Benko E, Huibner S, Kovacs CM, Singer J, Kim CJ, Kaul R. Randomized, Blinded, Placebo-Controlled Trial of De Simone Formulation Probiotic During HIV-Associated Suboptimal CD4+ T Cell Recovery. J Acquir Immune Defic Syndr. 2022 Feb 1;89(2):199-207. doi: 10.1097/QAI.0000000000002840.
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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.
Rupert Kaul, MD principal investigator
University Health Network, Toronto
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Visbiome in people with HIV-1 Infection, run by University Health Network, Toronto at 2 sites in Canada.
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 6 inclusion and 10 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: status not confirmed, as of the sponsor's last update on 18 Apr 2018. 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 Canada. 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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Rupert Kaul, MD (416-978-8607, rupert.kaul@utoronto.ca), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Percent change in blood immune activation (time frame: 48 weeks). 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 NCT02441231, 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 18 Apr 2018.