Probiotic Visbiome for Inflammation and Translocation in HIV II

HIV-1 Infection Clinical Trial

— PROOV IT II  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02441231
• Other study ID #: CTNPT 022B
• Status: Recruiting
• Phase: Phase 2
• First received: April 23, 2015
• Last updated: April 17, 2018
• Start date: November 2015
• Est. completion date: May 2019

Study information

• Verified date: April 2018
• Source: University Health Network, Toronto
• Contact: Rupert Kaul, MD
• Phone: 416-978-8607
• Email: rupert.kaul[@]utoronto.ca
• Is FDA regulated: No
• Study type: Interventional

Clinical 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. 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 36
• Est. completion date: May 2019
• Est. primary completion date: May 2019
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 19 Years and older

Eligibility

Inclusion Criteria:

• 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

Exclusion Criteria:

• 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

• 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

Related Conditions & MeSH terms

• HIV-1 Infection
• Inflammation

Intervention

Drug:
• Visbiome
Visbiome probiotic

Other:
• Placebo
Placebo

Locations

Country	Name	City	State
Canada	Maple Leaf Medical Clinic	Toronto	Ontario
Canada	Toronto General Hospital, UHN	Toronto	Ontario

Sponsors (2)

Lead Sponsor	Collaborator
University Health Network, Toronto	CIHR Canadian HIV Trials Network

Country where clinical trial is conducted

Canada, 

Outcome

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