Pilot Trial of a Synbiotic in HIV+ Patients

HIV Infection Clinical Trial

Official title:

Pilot Trial of a Synbiotic in HIV+ Patients

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00688311
• Other study ID #: 200715524-1
• Status: Completed
• Phase: N/A
• First received: May 16, 2008
• Last updated: November 19, 2009
• Start date: May 2008
• Est. completion date: November 2009

Study information

• Verified date: November 2009
• Source: University of California, Davis
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial Summary

The goal of this study is to test the hypothesis that daily ingestion of a 'synbiotic' for 4 weeks will improve intestinal function, ease immune system overactivation, and increase blood CD4 count in HIV-infected individuals. A 'Synbiotic' is a mixture of probiotic bacteria and dietary fiber.

Description:

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 34
• Est. completion date: November 2009
• Est. primary completion date: November 2009
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• HIV seropositive

• Adult Female

• Currently taking antiretroviral medication

Exclusion Criteria:

• AIDS-defining conditions

• Current use of oral antibiotics

• Inflammatory bowel disease or other known GI pathology

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator), Primary Purpose: Supportive Care

Related Conditions & MeSH terms

• HIV Infection

Intervention

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).
• Placebo
Placebo

Locations

Country	Name	City	State
United States	CARES Clinic	Sacramento	California

Sponsors (1)

Lead Sponsor	Collaborator
University of California, Davis

Country where clinical trial is conducted

United States, 

References & Publications (4)

Brenchley JM, Price DA, Schacker TW, Asher TE, Silvestri G, Rao S, Kazzaz Z, Bornstein E, Lambotte O, Altmann D, Blazar BR, Rodriguez B, Teixeira-Johnson L, Landay A, Martin JN, Hecht FM, Picker LJ, Lederman MM, Deeks SG, Douek DC. Microbial translocation is a cause of systemic immune activation in chronic HIV infection. Nat Med. 2006 Dec;12(12):1365-71. Epub 2006 Nov 19. — View Citation

Kotzampassi K, Giamarellos-Bourboulis EJ, Voudouris A, Kazamias P, Eleftheriadis E. Benefits of a synbiotic formula (Synbiotic 2000Forte) in critically Ill trauma patients: early results of a randomized controlled trial. World J Surg. 2006 Oct;30(10):1848-55. — View Citation

Rayes N, Seehofer D, Theruvath T, Mogl M, Langrehr JM, Nüssler NC, Bengmark S, Neuhaus P. Effect of enteral nutrition and synbiotics on bacterial infection rates after pylorus-preserving pancreatoduodenectomy: a randomized, double-blind trial. Ann Surg. 2007 Jul;246(1):36-41. — View Citation

Rayes N, Seehofer D, Theruvath T, Schiller RA, Langrehr JM, Jonas S, Bengmark S, Neuhaus P. Supply of pre- and probiotics reduces bacterial infection rates after liver transplantation--a randomized, double-blind trial. Am J Transplant. 2005 Jan;5(1):125-30. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Plasma Lipopolysaccharide		4 weeks	No
Secondary	Immune Activation		4 weeks	No