Pilot Trial of a Synbiotic in HIV+ Patients
|Study Design:||Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Supportive Care
|Official Title:||Pilot Trial of a Synbiotic in HIV+ Patients|
- Plasma Lipopolysaccharide [ Time Frame: 4 weeks ] [ Designated as safety issue: No ]
- Immune Activation [ Time Frame: 4 weeks ] [ Designated as safety issue: No ]
|Study Start Date:||May 2008|
|Study Completion Date:||November 2009|
|Primary Completion Date:||November 2009 (Final data collection date for primary outcome measure)|
Ingestion of synbiotic dietary supplement
Dietary Supplement: Synbiotic 2000
A preparation consisting of 4 species of probiotic bacteria (10^10 each) combined with 4 types of dietary fiber (2.5g each).
Other Name: Synbiotic 2000, Medipharm, Kagerod, Sweden
Placebo Comparator: Placebo
Ingestion of the Placebo
Dietary Supplement: Placebo
RATIONALE. HIV infection results in alterations to the intestinal tract, even in clinically healthy patients. Changes may include pronounced CD4 T-cell loss, enteric nerve and smooth muscle degeneration, abnormal enterocyte morphology, altered gene expression patterns, increased intestinal permeability, and decreased absorptive capacity. Recently it was found that HIV infection may also result in abnormal low-level leakage of lipopolysaccharide (LPS, a gram-negative bacterial product) from the gut into the circulation which promotes systemic immune activation. As immune activation is a strong positive correlate of HIV disease progression, it may be very important to develop effective means to improve intestinal barrier function in HIV infection. Evidence also exists that uninfected individuals of African descent may have higher intestinal permeability than uninfected Caucasians, suggesting that intestinal dysfunction in the event of HIV infection could differ between the two races. With regard to gender, women have been shown to display more pronounced inflammatory responses to LPS compared to men. Intriguing research outside the HIV field using animal models of compromised gut barrier function and also using human subjects with trauma- or disease-associated intestinal leakage has shown that oral administration of certain probiotic bacteria can 1) Reduce bacterial translocation, 2) Reduce bacterial infections, 3) Decrease inflammatory cytokines, and 4) Improve survival. Thus, probiotics could offer important benefits to HIV infected patients by improving intestinal function and reducing subsequent microbial translocation and immune activation. These benefits may vary by race.
OBJECTIVE. To determine the effect of an oral synbiotic supplement (Synbiotic 2000) on plasma LPS levels, systemic immune activation, and blood CD4 count in HIV infected women.
HYPOTHESIS. Oral treatment of HIV+ patients with this synbiotic supplement will improve intestinal barrier function, decrease the translocation of LPS into the circulation, and result in reduced systemic immune activation and improved CD4 count.
EXPERIMENTAL DESIGN. 30 HIV+ female subjects will be randomized to test supplement or placebo and undergo a baseline blood draw to establish initial values for plasma LPS, immune activation markers, and blood CD4 count. Following daily ingestion of the test supplement or placebo for 4 weeks, subjects will undergo a second blood draw for measurement of the same factors. Subjects will also provide a stool specimen at the beginning and end of the 4 week period.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00688311
|United States, California|
|Sacramento, California, United States, 95811|
|Principal Investigator:||Bill Critchfield, Ph.D.||University of California, Davis|