Probiotic Visbiome for Inflammation and Translocation in HIV Ι

HIV-1 Infection Clinical Trial

— PROOV IT I  

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02441244
• Other study ID #: CTNPT 022A
• Status: Terminated
• Phase: Phase 2
• First received: April 23, 2015
• Last updated: February 27, 2018
• Start date: November 15, 2015
• Est. completion date: December 19, 2016

Study information

• Verified date: February 2018
• Source: University Health Network, Toronto
• Contact: n/a
• 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 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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 1
• Est. completion date: December 19, 2016
• Est. primary completion date: December 19, 2016
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 19 Years and older

Eligibility

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

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		24 weeks
Other	Bacterial community diversity, determined by 16s rRNA gene sequencing of penile swabs		24 weeks
Other	Bacterial community composition, determined by 16s rRNA gene sequencing of penile swabs		24 weeks
Other	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
Other	Level of microbial translocation (including LPS and sCD14) (open-label)		48 weeks
Other	Plasma levels of inflammation and coagulation (including IL-6, D-dimer and CRP) (open-label)		48 weeks
Other	Number and function of gut immune cells (including CD4 T cell subsets) (open-label)		48 weeks
Other	Intestinal permeability (Lac/Man) (open-label)		48 weeks
Other	Microbiome analysis by 16s rRNA bacterial DNA isolated from penile swabs (open-label)		48 weeks
Other	Gut HIV DNA levels (open-label)		48 weeks
Other	Canadian Diet History Questionnaire (open-label)		48 weeks
Other	Safety (open-label) assessed by AE monitoring and participant questionnaire		48 weeks
Other	Tolerability of Visbiome (open-label) assessed by AE monitoring and participant questionnaire		48 weeks
Other	Adherence to probiotic Visbiome (open-label) assessed by participant questionnaire and sachet count		48 weeks
Primary	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	Level of microbial translocation (including LPS and sCD14)		24 weeks
Secondary	Plasma level of inflammation and coagulation (including IL-6, D-dimer and CRP)		24 weeks
Secondary	Number and function of gut immune cells (including CD4 T cell subsets)		24 weeks
Secondary	Intestinal permeability (Lac/Mac ratio)		24 weeks
Secondary	Microbiome analysis by 16s rRNA bacterial DNA isolated from gut tissue and anal swabs		24 weeks
Secondary	Gut HIV DNA levels		24 weeks
Secondary	Canadian Diet History Questionnaire		24 weeks
Secondary	Safety assessed by AE monitoring and participant questionnaire		24 weeks
Secondary	Tolerability of Visbiome assessed by AE monitoring and participant questionnaire		24 weeks
Secondary	Adherence to probiotic Visbiome assessed by participant questionnaire and sachet count		24 weeks