Back to results

Trial of Probiotics to Lower Microbial Translocation and Immune Activation in HIV-Infected Adolescents

Primary Purpose

HIV Infection

Status

Withdrawn

Phase

Not Applicable

Locations

Study Type

Interventional

Intervention

Probiotics

Placebo

About this trial

This is an interventional supportive care trial for HIV Infection focused on measuring HIV infection, Probiotics

Eligibility Criteria

13 Years - 24 Years (Child, Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

To be considered eligible for enrollment, an individual must meet the criteria listed below.

Age 13 years and 0 days to 24 years and 364 days at the time of consent
Confirmed or suspected to have acquired HIV infection at age 10 years or older
HIV-1 infection as documented by any FDA-approved ELISA test kit and confirmed by Western blot, HIV-1 culture, HIV-1 antigen, HIV-1 DNA, plasma HIV-1 RNA, or a second antibody test by a method other than ELISA at any time prior to pre-entry
Absolute CD4 T-cell count greater than 350 cells/ul at pre-entry
Cohort 1 - Not receiving ART and no exposure to ART in the 24 weeks prior to pre-entry: Quantitative HIV-1 plasma RNA (viral load) less than 50,000 copies/ml on two consecutive determinations at least 8 weeks apart in the 24 weeks prior to and including pre-entry
Cohort 2 - Currently receiving ART and received ART for at least the 24 weeks prior to pre-entry: Quantitative HIV-1 plasma RNA (viral load) less than 400 copies/ml on two consecutive determinations at least 8 weeks apart in the 24 weeks prior to and including pre-entry
Willingness to refrain from regular use of foods/supplements containing probiotics other than that supplied by the study during the course of study participation

Exclusion Criteria:

To be considered eligible for enrollment, an individual must not meet any of the criteria listed below.

Known hypersensitivity to probiotics
Active AIDS-defining condition or acute serious illness
Cohort 1 - Not receiving ART and no exposure to ART in the 24 weeks prior to pre-entry: Any quantitative HIV-1 plasma RNA (viral load) equal to or greater than 50,000 copies/ml during the 24 weeks prior or at pre-entry.
Cohort 2 - Currently receiving ART and received ART for at least the 24 weeks prior to pre-entry: Any quantitative HIV-1 plasma RNA (viral load) equal to or greater than 400 copies/ml during the 24 weeks prior or at pre-entry
Known history of inflammatory bowel disease or similar disorder of the GI tract
Current treatment with immune-modulating or immune-suppressive therapy
Active malignancy at pre-entry
Pregnancy
Grade 3 or higher clinical or laboratory toxicities at the time of randomization
Regular use of foods or supplements containing probiotics within the 2 weeks prior to randomization (see Appendix V)
Concurrent participation in the ATN 061, 071, 081, and/or 101 protocols

Sites / Locations

Arms of the Study

Arm 1

Arm 2

Arm Type

Placebo Comparator

Experimental

Arm Label

Placebo

Probiotics

Arm Description

Subjects randomized to the placebo arm.

The probiotics use in the study contains two strains of Lactobacillus plantarum. Each dose of the active study agent contains contains 1 g maltodextrin plus the probiotic bacteria Lp299v (5 x 109 cfu) and Lp299 (5 x 109 cfu).

Outcomes

Primary Outcome Measures

Plasma LPS levels

To determine if once daily probiotic therapy decreases microbial translocation in HIV-infected youth as measured by changes in plasma LPS.

Secondary Outcome Measures

Stool colonization with Lactobacillus plantarum

To quantify the extent that Lactobacillus plantarum populates fecal samples obtained over time in HIV-infected youth receiving probiotics.

Plasma pro-inflammatory cytokines and macrophage activation

To determine if probiotic colonization of the gastrointestinal (GI) tract with Lactobacillus plantarum decreases levels of plasma pro-inflammatory cytokines and macrophage activation by measuring tumor necrosis factor alpha (TNFα), interferon alpha (IFNα), interleukin-1 beta (IL-1β), interleukin-6 (IL-6), interleukin-12p70 (IL-12p70), interleukin-10 (IL-10), and soluble CD14 (sCD14) as well as other markers of microbial translocation.

Lymphocyte activation markers

To determine if probiotic colonization of the GI tract with Lactobacillus plantarum results in decreased levels of T-cell activation markers as measured by shedding of soluble CD27 (sCD27), proportion of CD4 Th17 subsets, and expression of CD38 and HLA DR on CD8 T cells within ART treated and untreated HIV-infected youth.

Quantitative HIV-1 plasma RNA (viral load) and CD4 T-cell count

To examine if probiotics have any impact on quantitative HIV-1 plasma RNA (viral load) and CD4 T-cell count among the study cohort.

Stool microbial composition and genetic diversity

To molecularly characterize changes in overall bacteria diversity within the stool specimens of youth treated with probiotics.

Safety labs and adverse events as a measure of acceptability and tolerability of probiotics

To examine the acceptability and tolerability of probiotics when administered to HIV-infected youth.

Food frequency and probiotics and lifestyle questionnaires

To explore the effect of diet, smoking, and dietary supplements on plasma pro-inflammatory cytokine levels.

Full Information

NCT ID

NCT01492803

First Posted

November 4, 2011

Last Updated

February 27, 2017

Sponsor

University of North Carolina, Chapel Hill

Collaborators

National Institute on Drug Abuse (NIDA), National Institute of Mental Health (NIMH)

1. Study Identification

Unique Protocol Identification Number

NCT01492803

Brief Title

Trial of Probiotics to Lower Microbial Translocation and Immune Activation in HIV-Infected Adolescents

Official Title

A Randomized Placebo-Controlled Trial of Probiotics to Lower Microbial Translocation and Immune Activation in HIV-Infected Adolescents

Study Type

Interventional

2. Study Status

Record Verification Date

February 2016

Overall Recruitment Status

Withdrawn

Study Start Date

December 2011 (undefined)

Primary Completion Date

December 2012 (Anticipated)

Study Completion Date

December 2012 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

University of North Carolina, Chapel Hill

Collaborators

National Institute on Drug Abuse (NIDA), National Institute of Mental Health (NIMH)

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

This is a randomized placebo-controlled trial to examine if once daily probiotic therapy will lower serum LPS levels and immune activation among HIV-infected youth.

Detailed Description

This is a double masked randomized placebo-controlled trial to examine if once daily probiotic therapy will lower serum lipopolysaccharide (LPS) levels and immune activation among HIV-infected youth. The study will enroll two cohorts: (1) a cohort of subjects who are not receiving antiretroviral therapy (ART) and have absolute CD4 T-cell count greater than 350 cells/ul and quantitative HIV-1 plasma RNA (viral load) less than 50,000 copies/ml; and (2) a cohort of subjects who are receiving ART and have absolute CD4 T-cell count greater than 350 cells/ul and and quantitative HIV-1 plasma RNA (viral load) less than 400 copies/ml.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

HIV Infection

Keywords

HIV infection, Probiotics

7. Study Design

Primary Purpose

Supportive Care

Study Phase

Not Applicable

Interventional Study Model

Parallel Assignment

Masking

ParticipantCare ProviderInvestigator

Allocation

Randomized

Enrollment

0 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Placebo

Arm Type

Placebo Comparator

Arm Description

Subjects randomized to the placebo arm.

Arm Title

Probiotics

Arm Type

Experimental

Arm Description

Intervention Type

Dietary Supplement

Intervention Name(s)

Probiotics

Other Intervention Name(s)

No other names.

Intervention Description

Probiotic is a live microorganism that when administered in adequate amounts confer a health benefit on the host. It is classified by the FDA as "generally recognized as safe" (GRAS)

Intervention Type

Dietary Supplement

Intervention Name(s)

Placebo

Intervention Description

The placebo sticks will contain approximately 1 g maltodextrin

Primary Outcome Measure Information:

Title

Plasma LPS levels

Description

To determine if once daily probiotic therapy decreases microbial translocation in HIV-infected youth as measured by changes in plasma LPS.

Time Frame

32 Weeks

Secondary Outcome Measure Information:

Title

Stool colonization with Lactobacillus plantarum

Description

To quantify the extent that Lactobacillus plantarum populates fecal samples obtained over time in HIV-infected youth receiving probiotics.

Time Frame

32 Weeks

Title

Plasma pro-inflammatory cytokines and macrophage activation

Description

Time Frame

32 Weeks

Title

Lymphocyte activation markers

Description

Time Frame

32 Weeks

Title

Quantitative HIV-1 plasma RNA (viral load) and CD4 T-cell count

Description

To examine if probiotics have any impact on quantitative HIV-1 plasma RNA (viral load) and CD4 T-cell count among the study cohort.

Time Frame

32 Weeks

Title

Stool microbial composition and genetic diversity

Description

To molecularly characterize changes in overall bacteria diversity within the stool specimens of youth treated with probiotics.

Time Frame

32 Weeks

Title

Safety labs and adverse events as a measure of acceptability and tolerability of probiotics

Description

To examine the acceptability and tolerability of probiotics when administered to HIV-infected youth.

Time Frame

32 Weeks

Title

Food frequency and probiotics and lifestyle questionnaires

Description

To explore the effect of diet, smoking, and dietary supplements on plasma pro-inflammatory cytokine levels.

Time Frame

32 Weeks

10. Eligibility

Sex

All

Minimum Age & Unit of Time

13 Years

Maximum Age & Unit of Time

24 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: To be considered eligible for enrollment, an individual must meet the criteria listed below. Age 13 years and 0 days to 24 years and 364 days at the time of consent Confirmed or suspected to have acquired HIV infection at age 10 years or older HIV-1 infection as documented by any FDA-approved ELISA test kit and confirmed by Western blot, HIV-1 culture, HIV-1 antigen, HIV-1 DNA, plasma HIV-1 RNA, or a second antibody test by a method other than ELISA at any time prior to pre-entry Absolute CD4 T-cell count greater than 350 cells/ul at pre-entry Cohort 1 - Not receiving ART and no exposure to ART in the 24 weeks prior to pre-entry: Quantitative HIV-1 plasma RNA (viral load) less than 50,000 copies/ml on two consecutive determinations at least 8 weeks apart in the 24 weeks prior to and including pre-entry Cohort 2 - Currently receiving ART and received ART for at least the 24 weeks prior to pre-entry: Quantitative HIV-1 plasma RNA (viral load) less than 400 copies/ml on two consecutive determinations at least 8 weeks apart in the 24 weeks prior to and including pre-entry Willingness to refrain from regular use of foods/supplements containing probiotics other than that supplied by the study during the course of study participation Exclusion Criteria: To be considered eligible for enrollment, an individual must not meet any of the criteria listed below. Known hypersensitivity to probiotics Active AIDS-defining condition or acute serious illness Cohort 1 - Not receiving ART and no exposure to ART in the 24 weeks prior to pre-entry: Any quantitative HIV-1 plasma RNA (viral load) equal to or greater than 50,000 copies/ml during the 24 weeks prior or at pre-entry. Cohort 2 - Currently receiving ART and received ART for at least the 24 weeks prior to pre-entry: Any quantitative HIV-1 plasma RNA (viral load) equal to or greater than 400 copies/ml during the 24 weeks prior or at pre-entry Known history of inflammatory bowel disease or similar disorder of the GI tract Current treatment with immune-modulating or immune-suppressive therapy Active malignancy at pre-entry Pregnancy Grade 3 or higher clinical or laboratory toxicities at the time of randomization Regular use of foods or supplements containing probiotics within the 2 weeks prior to randomization (see Appendix V) Concurrent participation in the ATN 061, 071, 081, and/or 101 protocols

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

John Sleasman, MD

Organizational Affiliation

University of South Florida

Official's Role

Study Chair

12. IPD Sharing Statement

Learn more about this trial

Trial of Probiotics to Lower Microbial Translocation and Immune Activation in HIV-Infected Adolescents

We'll reach out to this number within 24 hrs