Probiotic Visbiome for Inflammation and Translocation in HIV II

NCT02441231 | Unknown Phase 2 DMC

• 1 other identifier: CTNPT 022B
• Study Type: interventional
• Target: 36
• 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 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.

Conditions

HIV-1 Infection

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (11)

• Level of microbial translocation (including LSP and sCD14)

  48 weeks

• Plasma level of inflammation and coagulation (including IL-6, D-dimer and CRP)

  48 weeks

• Number and function of gut immune cells (including CD4 T cell subsets)

  48 weeks

• Intestinal permeability (Lac/Mac ratio)

  48 weeks

• Bacterial community diversity, determined by 16s rRNA gene sequencing of penile swabs

  48 weeks

Other Outcomes (2)

• Metabolomic measurements: vitamin D levels, glucose measurements, insulin levels and lipid profiling

  48 weeks

• Microbiome analysis by 16s rRNA bacterial DNA isolated from penile swabs

  48 weeks

Study Arms (2)

Probiotic Group

EXPERIMENTAL

Visbiome probiotic 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)
• 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

You may not qualify if:

• 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

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

RECRUITING

Toronto General Hospital, UHN

Toronto, Ontario, M5G 2N2, Canada

RECRUITING

Related Publications (1)

• Rousseau RK, Walmsley SL, Lee T, Rosenes R, Reinhard RJ, Malazogu F, Benko E, Huibner S, Kovacs CM, Singer J, Kim CJ, Kaul R. Randomized, Blinded, Placebo-Controlled Trial of De Simone Formulation Probiotic During HIV-Associated Suboptimal CD4+ T Cell Recovery. J Acquir Immune Defic Syndr. 2022 Feb 1;89(2):199-207. doi: 10.1097/QAI.0000000000002840.

  PMID: 34693932 DERIVED

Study Officials

• Rupert Kaul, MD

  University Health Network, Toronto

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Rupert Kaul, MD

CONTACT

416-978-8607; rupert.kaul@utoronto.ca

Rodney Rousseau

CONTACT

416-946-7054; r.rousseau@mail.utoronto.ca

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 1, 2015
• Primary Completion: May 1, 2019
• Study Completion: May 1, 2019
• Last Updated: April 18, 2018

Record last verified: 2018-04

Locations

CA (2)