Probiotic Visbiome for Inflammation and Translocation in HIV II

NCT ID: NCT02441231

Last Updated: 2018-04-18

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE2
• Total Enrollment: 36 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-11-30
• Study Completion Date: 2019-05-31

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

Probiotic Group

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

Group Type: EXPERIMENTAL

Visbiome

Intervention Type: DRUG

Visbiome probiotic

Placebo Group

Placebo comparator group

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: OTHER

Placebo

Interventions

Visbiome

Visbiome probiotic

Intervention Type: DRUG

Placebo

Placebo

Intervention Type: OTHER

Eligibility Criteria

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

• Minimum Eligible Age: 19 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: No

Sponsors

CIHR Canadian HIV Trials Network

NETWORK

Sponsor Role: collaborator

University Health Network, Toronto

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Rupert Kaul, MD

Role: PRINCIPAL_INVESTIGATOR

University Health Network, Toronto

Locations

Maple Leaf Medical Clinic

Toronto, Ontario, Canada

Site Status: RECRUITING

Toronto General Hospital, UHN

Toronto, Ontario, Canada

Site Status: RECRUITING

Countries

Canada

Central Contacts

Rupert Kaul, MD

Role: CONTACT

rupert.kaul@utoronto.ca

416-978-8607

Rodney Rousseau

Role: CONTACT

r.rousseau@mail.utoronto.ca

416-946-7054

Facility Contacts

Colin Kovacs, MD

Role: primary

ckovacs@mlmedical.com

416-465-3252

Sharon Walmsley, MD

Role: primary

sharon.walmsley@uhn.ca

416-340-3871

References

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.

Reference Type: DERIVED

PMID: 34693932 (View on PubMed)

Other Identifiers

CTNPT 022B

Identifier Type: -

Identifier Source: org_study_id