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

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

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.

Study Overview

• Status: Terminated
• Conditions: HIV-1 Infection
• Intervention / Treatment: Other: Placebo; Drug: Visbiome

• Study Type: Interventional
• Enrollment (Actual): 1
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada, M5G 1K2
      • Maple Leaf Medical Clinic
    • Toronto, Ontario, Canada, M5G 2N2
      • Toronto General Hospital, UHN

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 19 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: TRIPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Blood immune activation	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	24 weeks

Secondary Outcome Measures

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Metabolomic measurements: vitamin D levels, glucose measurements, insulin levels and lipid profiling		24 weeks
Bacterial community diversity, determined by 16s rRNA gene sequencing of penile swabs		24 weeks
Bacterial community composition, determined by 16s rRNA gene sequencing of penile swabs		24 weeks
Blood immune activation (open-label)	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	48 weeks
Level of microbial translocation (including LPS and sCD14) (open-label)		48 weeks
Plasma levels of inflammation and coagulation (including IL-6, D-dimer and CRP) (open-label)		48 weeks
Number and function of gut immune cells (including CD4 T cell subsets) (open-label)		48 weeks
Intestinal permeability (Lac/Man) (open-label)		48 weeks
Microbiome analysis by 16s rRNA bacterial DNA isolated from penile swabs (open-label)		48 weeks
Gut HIV DNA levels (open-label)		48 weeks
Canadian Diet History Questionnaire (open-label)		48 weeks
Safety (open-label) assessed by AE monitoring and participant questionnaire		48 weeks
Tolerability of Visbiome (open-label) assessed by AE monitoring and participant questionnaire		48 weeks
Adherence to probiotic Visbiome (open-label) assessed by participant questionnaire and sachet count		48 weeks

Collaborators and Investigators

• Sponsor: University Health Network, Toronto
• Collaborators: CIHR Canadian HIV Trials Network

Study record dates

Study Major Dates

• Study Start (ACTUAL): November 15, 2015
• Primary Completion (ACTUAL): December 19, 2016
• Study Completion (ACTUAL): December 19, 2016

Study Registration Dates

• First Submitted: April 23, 2015
• First Submitted That Met QC Criteria: May 11, 2015
• First Posted (ESTIMATE): May 12, 2015

Study Record Updates

• Last Update Posted (ACTUAL): March 1, 2018
• Last Update Submitted That Met QC Criteria: February 27, 2018
• Last Verified: February 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Inflammation
• Other Study ID Numbers: CTNPT 022A