Clinical trial NCT02441231: Probiotic Visbiome for Inflammation and Translocation in HIV II
Official title: Probiotic Visbiome for Inflammation and Translocation in HIV II (PROOV IT II)
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: HIV-1 Infection
Lead sponsor: University Health Network, Toronto
Sponsor class: OTHER
Collaborators: name: CIHR Canadian HIV Trials Network
First posted: 2015-05-12
Enrollment: 36
Sex: MALE
Minimum age (years): 19
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: Percent change in blood immune activation
timeFrame: 48 weeks
Secondary outcomes:
measure: Level of microbial translocation (including LSP and sCD14)
timeFrame: 48 weeks
measure: Plasma level of inflammation and coagulation (including IL-6, D-dimer and CRP)
timeFrame: 48 weeks
measure: Number and function of gut immune cells (including CD4 T cell subsets)
timeFrame: 48 weeks
measure: Intestinal permeability (Lac/Mac ratio)
timeFrame: 48 weeks
measure: Bacterial community diversity, determined by 16s rRNA gene sequencing of penile swabs
timeFrame: 48 weeks
measure: Bacterial community composition, determined by 16s rRNA gene sequencing of penile swabs
timeFrame: 48 weeks
measure: Gut HIV DNA levels
timeFrame: 48 weeks
measure: Canadian Diet History Questionnaire
timeFrame: 48 weeks
measure: Safety assessed by AE monitoring and participant questionnaire
timeFrame: 48 weeks
measure: Tolerability of Visbiome assessed by AE monitoring and participant questionnaire
timeFrame: 48 weeks
measure: Adherence to Visbiome assessed by participant questionnaire and sachet count
timeFrame: 48 weeks
Other outcomes:
measure: Metabolomic measurements: vitamin D levels, glucose measurements, insulin levels and lipid profiling
timeFrame: 48 weeks
measure: Microbiome analysis by 16s rRNA bacterial DNA isolated from penile swabs
timeFrame: 48 weeks
Locations:
city: Toronto
country: Canada
facility: Maple Leaf Medical Clinic
state: Ontario
city: Toronto
country: Canada
facility: Toronto General Hospital, UHN
state: Ontario
Study officials:
affiliation: University Health Network, Toronto
name: Rupert Kaul, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.