Probiotic Visbiome for Inflammation and Translocation in HIV Ι

NCT02441244 | Terminated Phase 2 DMC

• 1 other identifier: CTNPT 022A
• Study Type: interventional
• Target: 1
• Locations: 1 country
• Sites: 2

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.

Conditions

HIV-1 Infection

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (10)

• 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

Other Outcomes (14)

• 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

Study Arms (2)

Probiotic Group

EXPERIMENTAL

Visbiome experimental group (900 billion bacteria daily; 2 sachets daily)

Drug: Visbiome

Placebo Group

PLACEBO COMPARATOR

Placebo comparator group

Other: Placebo

Interventions

Visbiome DRUG

Visbiome probiotic

Probiotic Group

Placebo OTHER

Placebo

Placebo Group

Eligibility Criteria

• Age: 19 Years+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University Health Network, Toronto: lead
• CIHR Canadian HIV Trials Network: collaborator

Study Sites (2)

Maple Leaf Medical Clinic

Toronto, Ontario, M5G 1K2, Canada

Location

Toronto General Hospital, UHN

Toronto, Ontario, M5G 2N2, Canada

Location

Study Officials

• Rupert Kaul, MD

  University Health Network, Toronto

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 23, 2015
• First Posted: May 12, 2015
• Study Start: November 15, 2015
• Primary Completion: December 19, 2016
• Study Completion: December 19, 2016
• Last Updated: March 1, 2018

Record last verified: 2018-02

Locations

CA (2)