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Probiotic Visbiome for Inflammation and Translocation in HIV Ι (PROOV IT I)

This study is currently recruiting participants.
Verified March 2016 by University Health Network, Toronto
Sponsor:
ClinicalTrials.gov Identifier:
NCT02441244
First Posted: May 12, 2015
Last Update Posted: March 11, 2016
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
Collaborator:
CIHR Canadian HIV Trials Network
Information provided by (Responsible Party):
University Health Network, Toronto
  Purpose

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 common among people living with HIV, 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 antiretroviral therapy (ART) will improve gut CD4 T cell restoration and function and therefore reduce microbial translocation and immune activation.

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 a phenotype that is associated with reduce inflammation, and Visbiome was also protective in a non-human primate model of SIV infection. Therefore, we believe that the "beneficial" bacteria from Visbiome will accelerate the normalization of gut immune cells and function in HIV-infected individuals as they start ART. Early resolution of gut immune cells may normalize microbial translocation and immune activation and will reduce the rates of HIV-associated comorbidities.


Condition Intervention Phase
HIV-1 Infection Drug: Visbiome Other: Placebo Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Probiotic Visbiome for Inflammation and Translocation in HIV I (PROOV IT I)

Resource links provided by NLM:


Further study details as provided by University Health Network, Toronto:

Primary Outcome Measures:
  • Blood immune activation [ Time Frame: 24 weeks ]
    Percent of blood immune activation (coexpression of CD38 and HLA-DR) on CD8 T cells at week 24 in participants randomized to probiotic Visbiome versus the placebo arm


Secondary Outcome Measures:
  • Level of microbial translocation (including LPS and sCD14) [ Time Frame: 24 weeks ]
  • Plasma level of inflammation and coagulation (including IL-6, D-dimer and CRP) [ Time Frame: 24 weeks ]
  • Number and function of gut immune cells (including CD4 T cell subsets) [ Time Frame: 24 weeks ]
  • Intestinal permeability (Lac/Mac ratio) [ Time Frame: 24 weeks ]
  • Microbiome analysis by 16s rRNA bacterial DNA isolated from gut tissue and anal swabs [ Time Frame: 24 weeks ]
  • Gut HIV DNA levels [ Time Frame: 24 weeks ]
  • Canadian Diet History Questionnaire [ Time Frame: 24 weeks ]
  • Safety assessed by AE monitoring and participant questionnaire [ Time Frame: 24 weeks ]
  • Tolerability of Visbiome assessed by AE monitoring and participant questionnaire [ Time Frame: 24 weeks ]
  • Adherence to probiotic Visbiome assessed by participant questionnaire and sachet count [ Time Frame: 24 weeks ]

Other Outcome Measures:
  • Metabolomic measurements: vitamin D levels, glucose measurements, insulin levels and lipid profiling [ Time Frame: 24 weeks ]
  • Bacterial community diversity, determined by 16s rRNA gene sequencing of penile swabs [ Time Frame: 24 weeks ]
  • Bacterial community composition, determined by 16s rRNA gene sequencing of penile swabs [ Time Frame: 24 weeks ]
  • Blood immune activation (open-label) [ Time Frame: 48 weeks ]
    Percent of blood immune activation (coexpression of CD38 and HLA-DR) on CD8 T cells at week 24 in participants randomized to probiotic Visbiome versus the placebo arm

  • Level of microbial translocation (including LPS and sCD14) (open-label) [ Time Frame: 48 weeks ]
  • Plasma levels of inflammation and coagulation (including IL-6, D-dimer and CRP) (open-label) [ Time Frame: 48 weeks ]
  • Number and function of gut immune cells (including CD4 T cell subsets) (open-label) [ Time Frame: 48 weeks ]
  • Intestinal permeability (Lac/Man) (open-label) [ Time Frame: 48 weeks ]
  • Microbiome analysis by 16s rRNA bacterial DNA isolated from penile swabs (open-label) [ Time Frame: 48 weeks ]
  • Gut HIV DNA levels (open-label) [ Time Frame: 48 weeks ]
  • Canadian Diet History Questionnaire (open-label) [ Time Frame: 48 weeks ]
  • Safety (open-label) assessed by AE monitoring and participant questionnaire [ Time Frame: 48 weeks ]
  • Tolerability of Visbiome (open-label) assessed by AE monitoring and participant questionnaire [ Time Frame: 48 weeks ]
  • Adherence to probiotic Visbiome (open-label) assessed by participant questionnaire and sachet count [ Time Frame: 48 weeks ]

Estimated Enrollment: 40
Study Start Date: November 2015
Estimated Study Completion Date: October 2017
Estimated Primary Completion Date: October 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Probiotic Group
Visbiome experimental group (900 billion bacteria daily; 2 sachets daily)
Drug: Visbiome
Visbiome probiotic
Placebo Comparator: Placebo Group
Placebo comparator group
Other: Placebo
Placebo

  Eligibility

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   19 Years and older   (Adult, Senior)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Documented HIV-1 infection
  • Male adult (age >18 years)
  • Antiretroviral therapy-naïve
  • Ability to provide informed consent
  • HIV-1 viral load ≥1,000 copies/ml

Exclusion Criteria:

  • Current alcohol or substance use judged by the Investigator to potentially interfere with participant 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
    • AST or ALT >5X the upper limit of normal
  • Malignancy
  • 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
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02441244


Contacts
Contact: Rupert Kaul, MD 416-978-8607 rupert.kaul@utoronto.ca
Contact: Connie Kim, PhD 416-946-7054 kim.connie@gmail.com

Locations
Canada, Ontario
Maple Leaf Medical Clinic Recruiting
Toronto, Ontario, Canada, M5G 1K2
Contact: Colin Kovacs, MD    416-465-3252    ckovacs@mlmedical.com   
Principal Investigator: Colin Kovacs, MD         
Toronto General Hospital, UHN Recruiting
Toronto, Ontario, Canada, M5G 2N2
Contact: Sharon Walmsley, MD    416-340-3871    sharon.walmsley@uhn.ca   
Principal Investigator: Sharon Walmsley, MD         
Sponsors and Collaborators
University Health Network, Toronto
CIHR Canadian HIV Trials Network
Investigators
Principal Investigator: Rupert Kaul, MD University Health Network, Toronto
  More Information

Responsible Party: University Health Network, Toronto
ClinicalTrials.gov Identifier: NCT02441244     History of Changes
Other Study ID Numbers: CTNPT 022A
First Submitted: April 23, 2015
First Posted: May 12, 2015
Last Update Posted: March 11, 2016
Last Verified: March 2016

Additional relevant MeSH terms:
Inflammation
Pathologic Processes