Rifaximin as a Modulator of Microbial Translocation and Immune Activation

NCT01466595 | Completed Phase 2 Results DMC

• 2 other identifiers: ACTG A52861U01AI068636
• Study Type: interventional
• Target: 73
• Locations: 2 countries
• Sites: 32

Brief Summary

This study is being done to see whether rifaximin, an antibiotic that works in the intestines, can lower the amount of germs in the intestines of HIV infected persons. It is possible that when the amount of these germs is lowered, an HIV-infected person's immune system will become less active and will have a better chance of recovering. Also, the study will evaluate the safety of using rifaximin in HIV-infected subjects.

Conditions

HIV-1 Infection

Outcome Measures

Primary Outcomes (1)

• Change in CD8+ T-cell Activation From Baseline to Week 4

  Change in CD8+ T-cell activation percent co-expressing HLA-DR and CD38 from baseline to week 4, where the baseline value is the average of pre-entry and entry values.

  At baseline and 4 weeks

Secondary Outcomes (42)

• Change in D-dimer From Baseline to Week 4

  At baseline and 4 weeks

• Change in IL-6 From Baseline to Week 4

  At baseline and 4 weeks

• Change in LPS From Baseline to Week 4

  At baseline and 4 weeks

• Change in hsCRP From Baseline to Week 4

  At baseline and 4 weeks

• Change in sCD14 From Baseline to Week 4

  At baseline and 4 weeks

Study Arms (2)

Arm A: Treatment with rifaximin

EXPERIMENTAL

Participants were administered one 550 mg tablet of rifaximin to be taken orally two times a day for 4 weeks.

Drug: Rifaximin

Arm B: No study treatment

NO INTERVENTION

No study treatment for 4 weeks

Interventions

Rifaximin DRUG

Participant were administered one 550 mg tablet of rifaximin to be taken orally two times a day for 4 weeks.

Arm A: Treatment with rifaximin

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• HIV-1 infection
• On ART for at least 96 weeks prior to study entry with a regimen that includes three or more antiretroviral medications. (Ritonavir ≤ 400 mg/day will not be considered a separate antiretroviral agent.)
• No plans to change the antiretroviral regimen at least in the next 3 months after study entry.
• CD4+ cell count \< 350 cells/mm3 obtained within 120 days prior to study entry at any laboratory that has a Clinical Laboratory Improvement Amendments (CLIA) certification or its equivalent.
• All previous CD4+ cell counts should be \< 350 cells/mm3 for at least 96 weeks prior to study entry while subjects were on ART. (A single CD4+ cell count ≥ 350 cells/mm3 is permitted within 96 weeks prior to study entry while subjects were on ART.)
• Documentation of HIV-1 RNA below the limit of detection (e.g., \< 50 copies/mL on Roche Amplicor HIV-1 Monitor assay, \< 75 copies/mL on the Versant HIV-1 RNA assay by branched DNA, \< 400 copies/mL on a standard Roche Amplicor assay, \< 40 copies/mL on the Abbott m2000sp/m2000rt real-time PCR test, \< 48 copies/mL on the COBAS AmpliPrep/TAQMAN HIV-1 assay) verified by at least two measurements prior to study entry, one of which must be at least 48 weeks prior to study entry and one measurement that was obtained between 121 days and 48 weeks prior to study entry.
• Screening HIV-1 RNA below the limit of detection obtained within 120 days prior to study entry using a FDA -approved assay (e.g., \< 50 copies/mL on Roche Amplicor HIV-1 Monitor assay, \< 75 copies/mL on the Versant HIV-1 RNA assay by branched DNA, \< 40 copies/mL on the Abbott m2000sp/m2000rt real-time PCR test, \< 48 copies/mL on the COBAS AmpliPrep/TAQMAN HIV-1 assay). (The virologic assay must have a lower limit of detection of ≤ 75 copies/mL.)
• All other plasma HIV-1 RNA measurements in the 48 weeks prior to study entry must be below the limit of detection. (A single detectable measurement of ≤ 200 copies/mL is permitted if RNA levels immediately before and after are below the limits of detection for the assay.)
• Certain fasting laboratory values obtained within 45 days prior to entry as indicated in Section 4.1.9 of the protocol.
• Pre-entry peripheral blood mononuclear cell (PBMC) specimen for assay of the primary immune activation endpoint (change in CD8+ T-cells activation (%HLA-DR+CD38+CD8+ T-cells) has been obtained. Sites must receive confirmation from the processing lab via phone, e-mail, or fax, that this specimen has been entered into the ACTG's Laboratory Data Management System (LDMS).
• Female subjects of reproductive potential must have a negative serum or urine β-HCG pregnancy test with a sensitivity of at least 50 mIU/mL performed within 24 hours prior to study entry.
• If participating in sexual activity that could lead to pregnancy, the female subject must agree to use one form of contraceptive as listed in section 4.1.11 of the protocol while receiving protocol-specified treatment and for 4 weeks after stopping the treatment.
• If the female subject is not of reproductive potential, she is eligible without requiring the use of a contraceptive. Self report is acceptable documentation of sterilization, other contraceptive methods, and menopause.
• Ability and willingness of subject or legally authorized representative to provide informed consent.

You may not qualify if:

• Active diarrhea (3 or more unformed stools per day) within 28 days prior to study entry (except if site investigator or primary care provider attributes diarrhea to antiretroviral or azithromycin use).
• History of or active inflammatory bowel disease.
• History of or active Clostridium difficile colitis.
• History of significant liver disease, defined as having chronic liver disease (including chronic alcoholic liver disease, hepatitis B or C), plus either: a) ascites, b) encephalopathy, or c) a Child-Pugh Score of \> 7.
• Receipt of antimicrobial therapy within 30 days prior to study entry. (NOTE: Antimicrobial use for prophylaxis of opportunistic infections, e.g., azithromycin or trimethoprim-sulfamethoxazole, is allowed.)
• Active infection requiring the use of antibiotics within 30 days prior to study entry.
• Known allergy/sensitivity or any hypersensitivity to components of study drug or their formulation (e.g., allergy to rifampin).
• Serious illness requiring systemic treatment and/or hospitalization within 14 days prior to entry.
• Use of any of the following medications for more than 3 consecutive days within the 60 days prior to study entry:
• Immunosuppressives
• Immune modulators
• Antineoplastic agents
• Probiotics
• Anticoagulants
• Vaccinations within 1 week prior to the pre-entry or study entry visits. (NOTE: Subjects are encouraged to get the flu vaccine prior to study pre-entry visit.)

Sponsors & Collaborators

• Advancing Clinical Therapeutics Globally for HIV/AIDS and Other Infections: lead
• National Institute of Allergy and Infectious Diseases (NIAID): collaborator

Study Sites (32)

Alabama Therapeutics CRS (5801)

Birmingham, Alabama, 35294, United States

Location

UCLA CARE Center CRS (601)

Los Angeles, California, 90095, United States

Location

Stanford CRS (501)

Palo Alto, California, 94304, United States

Location

Ucsf Aids Crs (801)

San Francisco, California, 94110, United States

Location

University of Colorado Hospital CRS (6101)

Aurora, Colorado, 80045, United States

Location

Georgetown University CRS (GU CRS) (1008)

Washington D.C., District of Columbia, 20007, United States

Location

Univ. of Miami AIDS CRS (901)

Miami, Florida, 33136, United States

Location

The Ponce de Leon Center CRS (5802)

Atlanta, Georgia, 30308, United States

Location

Northwestern University CRS (2701)

Chicago, Illinois, 60611, United States

Location

Rush Univ. Med. Ctr. ACTG CRS (2702)

Chicago, Illinois, 60612, United States

Location

IHV Baltimore Treatment CRS (4651)

Baltimore, Maryland, 21201, United States

Location

Massachusetts General Hospital ACTG CRS (101)

Boston, Massachusetts, 02114, United States

Location

Brigham and Women's Hosp. ACTG CRS (107)

Boston, Massachusetts, 02115, United States

Location

Beth Israel Deaconess Med. Ctr., ACTG CRS (103)

Boston, Massachusetts, 02215, United States

Location

Washington U CRS (2101)

St Louis, Missouri, 63110, United States

Location

New Jersey Medical School-Adult Clinical Research Ctr. CRS (31477)

Newark, New Jersey, 07103, United States

Location

Cornell CRS (7804)

New York, New York, 10011, United States

Location

NY Univ. HIV/AIDS CRS (401)

New York, New York, 10016, United States

Location

HIV Prevention & Treatment CRS (30329)

New York, New York, 10032, United States

Location

AIDS Care CRS (1108)

Rochester, New York, 14642, United States

Location

Univ. of Rochester ACTG CRS (1101)

Rochester, New York, 14642, United States

Location

Unc Aids Crs (3201)

Chapel Hill, North Carolina, 27516, United States

Location

Duke Univ. Med. Ctr. Adult CRS (1601)

Durham, North Carolina, 27710, United States

Location

Univ. of Cincinnati CRS (2401)

Cincinnati, Ohio, 45267, United States

Location

Case CRS (2501)

Cleveland, Ohio, 44106, United States

Location

Metro Health CRS (2503)

Cleveland, Ohio, 44109, United States

Location

The Ohio State Univ. AIDS CRS (2301)

Columbus, Ohio, 43210, United States

Location

Hosp. of the Univ. of Pennsylvania CRS (6201)

Philadelphia, Pennsylvania, 19104, United States

Location

Pittsburgh CRS (1001)

Pittsburgh, Pennsylvania, 15213, United States

Location

The Miriam Hosp. ACTG CRS (2951)

Providence, Rhode Island, 02906, United States

Location

University of Washington AIDS CRS (1401)

Seattle, Washington, 98104, United States

Location

Puerto Rico-AIDS CRS (5401)

San Juan, 00935, Puerto Rico

Location

Related Publications (1)

• Tenorio AR, Chan ES, Bosch RJ, Macatangay BJ, Read SW, Yesmin S, Taiwo B, Margolis DM, Jacobson JM, Landay AL, Wilson CC; A5286 Team. Rifaximin has a marginal impact on microbial translocation, T-cell activation and inflammation in HIV-positive immune non-responders to antiretroviral therapy - ACTG A5286. J Infect Dis. 2015 Mar 1;211(5):780-90. doi: 10.1093/infdis/jiu515. Epub 2014 Sep 11.

  PMID: 25214516 DERIVED

MeSH Terms

Interventions

Rifaximin

Intervention Hierarchy (Ancestors)

Rifamycins; Heterocyclic Compounds, 4 or More Rings; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Lactams, Macrocyclic; Macrocyclic Compounds; Polycyclic Compounds

Results Point of Contact

• Title: ACTG Clinicaltrials.gov Coordinator
• Organization: ACTG Network Coordinating Center, Social and Scientific Systems, Inc.

ACTGCT.Gov@s-3.com

(301) 628-3313

Study Officials

• Allan R. Tenorio, M.D.

  Rush University Medical Center

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 6, 2011
• First Posted: November 8, 2011
• Study Start: September 1, 2011
• Primary Completion: September 1, 2012
• Study Completion: November 1, 2012
• Last Updated: September 10, 2018
• Results First Posted: November 7, 2013

Record last verified: 2018-08

Locations

PR (1); US (31)