Probiotic Visbiome for Inflammation and Translocation in HIV Ι

Phase 2

Terminated

• Conditions: HIV-1 Infection
• Interventions: Drug: Visbiome; Other: Placebo

• Registration Number: NCT02441244
• Lead Sponsor: University Health Network, Toronto

Brief 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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2015-04-23
• Study First Submitted QC: 2015-05-11
• Study First Posted: 2015-05-12
• Study Start: 2015-11-15
• Primary Completion: 2016-12-19
• Study Completion: 2016-12-19
• Status Verified: 2018-02
• Last Update Submitted: 2018-02-27
• Last Update Posted: 2018-03-01

Recruitment & Eligibility

• Status: TERMINATED
• Sex: Male
• Target Recruitment: 1

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Probiotic Group	Visbiome	Visbiome experimental group (900 billion bacteria daily; 2 sachets daily)
Placebo Group	Placebo	Placebo comparator group

Primary Outcome Measures

Name	Time	Method
Blood immune activation	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

Name	Time	Method
Gut HIV DNA levels	24 weeks
Number and function of gut immune cells (including CD4 T cell subsets)	24 weeks
Tolerability of Visbiome assessed by AE monitoring and participant questionnaire	24 weeks
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
Intestinal permeability (Lac/Mac ratio)	24 weeks
Microbiome analysis by 16s rRNA bacterial DNA isolated from gut tissue and anal swabs	24 weeks
Canadian Diet History Questionnaire	24 weeks
Safety assessed by AE monitoring and participant questionnaire	24 weeks
Adherence to probiotic Visbiome assessed by participant questionnaire and sachet count	24 weeks

Trial Locations

Locations (2)

Toronto General Hospital, UHN; 🇨🇦 Toronto, Ontario, Canada

Maple Leaf Medical Clinic; 🇨🇦 Toronto, Ontario, Canada