Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Pilot Study of Oral Probiotic Bacteria Supplementation to Reduce Chronic Immune Activation in HIV-infected Malian Women

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02448238
Recruitment Status : Completed
First Posted : May 19, 2015
Last Update Posted : June 14, 2017
Sponsor:
Collaborator:
Bill and Melinda Gates Foundation
Information provided by (Responsible Party):
Virginia Commonwealth University

Brief Summary:

The composition of the intestinal bacterial flora effects gut immunologic function and intestinal barrier integrity. HIV infection impairs gut immune and epithelial function resulting in an altered gut bacterial flora and "leakage" of gut bacterial products into the bloodstream. These bacterial products can overstimulate the immune system leading to increased inflammation and HIV disease progression. The investigators will investigate whether oral supplementation of certain beneficial "probiotic" bacteria may attenuate these processes in HIV infected women in Mali, Africa.

This is a single arm study to evaluate the effect of 12 weeks of combination oral probiotic supplementation (VSL#3, Sigma-Tau Pharmaceuticals - containing 9 × 1011 bacteria of 8 species: S. thermophilus, Bifidobacterium breve, Bifidobacterium longum, Bifidobacterium infantis, Lactobacillus plantarum, Lactobacillus acidophilus, Lactobacillus paracasei, and Lactobacillus bulgaricus) on plasma biomarkers of immune cell activation, and inflammation. The study population will be 50 chronically HIV-infected but generally healthy, non-pregnant, Malian women subjects with CD4+ T-cell count ≥ 350 cells/mm3 who are not receiving antiretroviral therapy. Blood plasma/serum and fecal sampling will occur at baseline, 4, and 12 week as well as at 24 weeks. At these time points, probiotic will be dispensed, a medical history will be obtained, and adherence will be assessed. Prior to study entry, subjects will have eligibility and safety labs will be obtained and detailed baseline medical and symptom histories, demographics, weight, and stool frequency information will be recorded. A stress assessment questionnaire will be completed at baseline and week 12 to determine the effect of this intervention on stress levels.

The primary study outcome is to assess change (baseline to 12 week) in plasma soluble CD14 (a marker of monocyte response to bacterial endotoxin which has been associated with mortality) with study probiotic. Other outcomes will include assessing change (baseline to 12 week) in plasma interleukin-6, soluble CD163 (another monocyte activation marker), d-dimer (a marker of coagulopathy), intestinal fatty acid binding protein (a marker of gut epithelial cell injury) and fecal calprotectin (a marker of gut inflammation), as well as CD4+ T-cell counts, self reported stool quality (using the Bristol Stool Scale), safety and tolerability of the VSL#3 probiotic, and level of stress.


Condition or disease Intervention/treatment Phase
HIV Other: VSL#3® probiotic Not Applicable

  Show Detailed Description

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 23 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Supportive Care
Official Title: A Pilot Study of Oral Probiotic Bacteria Supplementation to Reduce Microbial Translocation and Chronic Immune Activation in HIV-infected Malian Women
Study Start Date : May 2015
Actual Primary Completion Date : March 2016
Actual Study Completion Date : March 2016

Resource links provided by the National Library of Medicine

MedlinePlus related topics: HIV/AIDS

Arm Intervention/treatment
Experimental: probiotic
This is a single arm study all subjects will receive the study VSL#3 probiotic. Subjects will take 1 sachet of powder orally daily for 12 weeks
Other: VSL#3® probiotic
Other: VSL#3® probiotic VSL#3® DS (Sigma-Tau Pharmaceuticals) is a well characterized water soluble, live (9 × 1011 bacteria/sachet), lyophilized preparation of 8 probiotic bacterium that have been detailed previously. Subjects will take 1 sachet of powder orally daily for 12 weeks. As many Malian homes lack refrigeration, subjects will be issued a special "canari", a commonly used earthenware water container also containing sand that works on the principal of "trans-evaporation" to keep contents at room temperature (~24°C) even in warmer climates. We have verified this in country. Probiotics will be placed in a sealed plastic bag within a sealed jar in the sand of the canari. At the research site, probiotics will be kept refrigerated (4-8°C) in a study provided refrigerator




Primary Outcome Measures :
  1. change in plasma soluble CD14 (sCD14) [ Time Frame: baseline to week 12 ]
    sCD14 is marker of monocyte response to endotoxin associated with mortality


Secondary Outcome Measures :
  1. change in plasma soluble CD163 (sCD163) [ Time Frame: baseline to week 12 ]
    sCD163 is a marker of monocyte activation associated with cardiovascular disease (CVD)

  2. change in plasma interleukin-6 (IL-6) [ Time Frame: baseline to week 12 ]
    IL-6 is associated with mortality and CVD

  3. change in plasma d-dimer [ Time Frame: baseline to week 12 ]
    d-dimer is associated with mortality and CVD

  4. change in plasma intestinal fatty acid biding protein [ Time Frame: baseline to week 12 ]
    intestinal fatty acid biding protein is associated with gut epithelial cell injury

  5. change in CD4+ T cell counts [ Time Frame: baseline to week 12 ]
    CD4 is associated with HIV disease progression

  6. change in fecal calprotectin [ Time Frame: baseline to week 12 ]
    fecal calprotectin is associated with gut inflammation

  7. change in stress levels [ Time Frame: baseline to week 12 ]
    uses standardized questionnaire

  8. number of participants with NIH/Department of AIDS Grade ≥ 2 signs and symptoms, Grade ≥ 2 laboratory abnormalities and other serious adverse events [ Time Frame: baseline to week 12 ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • HIV-1 infection, documented by any licensed rapid HIV test or HIV enzyme or chemiluminescence immunoassay (E/CIA) test kit at any time prior to study entry and confirmed by a licensed Western blot or a second antibody test by a method other than the initial rapid HIV and/or E/CIA, or by HIV-1 antigen, or plasma HIV-1 RNA viral load.
  • No plans to initiate ART during the course of the proposed study. NOTE: Subjects who meet WHO treatment guidelines for initiating ART once enrolled should begin therapy as clinically indicated. These subjects must stop study treatment, and will be followed on study/off study treatment.
  • Screening CD4+ T-cell count ≥ 350 cells/mm3 performed in a laboratory that has a Malian National Institute for Public Health and Research (INRSP) certification, or its equivalent, within 45 days prior to study entry.
  • Laboratory values obtained within 45 days prior to entry as follows:

    • Absolute neutrophil count (ANC) ≥ 1000/mm3
    • Hemoglobin ≥ 10.0 g/dL
    • Platelet count ≥ 50,000/mm3
  • Female subjects of reproductive potential [defined as girls who have reached menarche or women who have not been post-menopausal for at least 12 consecutive months, i.e., who have had menses within the preceding 12 months, or have not undergone surgical sterilization (e.g., hysterectomy, bilateral oophorectomy, or bilateral tubal ligation)] must have a negative serum or urine pregnancy test performed within 45 days prior to entry.
  • Female subjects participating in sexual activity that could lead to pregnancy must agree to use at least one of the following forms of birth control for at least 45 days prior to study entry until the final study visit:

    • Condoms (male or female) with or without a spermicidal agent
    • Diaphragm or cervical cap with spermicide
    • Intrauterine device (IUD)
    • Hormone-based contraceptive (pill, injection, implants)
  • Female subjects who are not of reproductive potential are eligible without requiring the use of a contraceptive. Acceptable documentation of sterilization, other contraception methods, menopause and reproductive potential is patient-reported history at any time prior to or during screening.
  • Malian women age => 18 years.
  • Ability and willingness of subject to provide informed consent.

Exclusion Criteria:

  • Pregnant.
  • Use of any antiretroviral agent during or within 24 weeks prior to study entry.
  • Use of any of the following medications for more than 3 consecutive days during or within 45 days prior to study entry:

    • Immunosuppressives
    • Immune modulators
    • Antineoplastic/Anticancer agents
    • Probiotics
    • Anticoagulants ( Aspirin is permitted )
  • Known allergy/sensitivity/intolerance to any probiotic formulation. Lactose intolerance is not exclusionary unless there was a hypersensitivity reaction
  • Active illicit drug or alcohol use or dependence, or conditions that, in the opinion of the site investigator, would interfere with adherence to study requirements.
  • Serious illness or trauma requiring systemic treatment and/or hospitalization within 45 days prior to study entry. Chronic stable conditions such as hypertension or diabetes are not exclusionary.
  • Anticipated antibiotic use during the study or use within 45 days prior to study entry. Topical antibiotics are permitted.
  • Known cirrhosis or severe liver disease (e.g., ascites, encephalopathy, history of variceal bleeding).
  • Recent (within 12 weeks) history of, or active, bowel obstruction, inflammatory bowel disease, colitis, intestinal bleeding, GI malignancy, or severe GI motility disorders including severe constipation or severe diarrhea (>5 stools day/average) or severe swallowing disorders.
  • Active gastrointestinal parasitic infection.
  • Major GI tract surgery within 45 days prior to study entry.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02448238


Locations
Layout table for location information
Mali
Nianankoro Fomba Hospital
Ségou, Ségou Region, Mali, BP169
Sponsors and Collaborators
Virginia Commonwealth University
Bill and Melinda Gates Foundation
Investigators
Layout table for investigator information
Principal Investigator: Daniel E Nixon, DO, PhD Virginia Commonwealth University, USA
Study Director: Saba Masho, MD, MPH Virginia Commonwealth University, USA
Study Director: Susan Kornstein, MD Virginia Commonwealth University, USA

Layout table for additonal information
Responsible Party: Virginia Commonwealth University
ClinicalTrials.gov Identifier: NCT02448238     History of Changes
Other Study ID Numbers: HM15330
VCUHIV001 ( Other Identifier: VCU )
First Posted: May 19, 2015    Key Record Dates
Last Update Posted: June 14, 2017
Last Verified: June 2017
Keywords provided by Virginia Commonwealth University:
Human Immunodeficiency Virus
probiotic
microbial translocation
immune activation
inflammation
VSL#3
Mali
Africa