Rifaximin for Chronic Immune Activation in People With HIV
Verified June 2014 by National Institutes of Health Clinical Center (CC)
University of Pittsburgh Division of Infectious Diseases
Walter Reed Navy MMC
Information provided by (Responsible Party):
National Institutes of Health Clinical Center (CC) ( National Cancer Institute (NCI) )
First received: May 29, 2013
Last updated: September 16, 2014
Last verified: June 2014
- Human immunodeficiency virus (HIV) treatment can control the amount of virus in the blood, but it does not provide a cure. The reasons why HIV treatment does not cure the infection are not well understood. HIV persists in blood cells for years, even if people receive treatment for it. In addition, HIV infection leads to an activated immune system, which can cause other problems.
- One theory for why HIV infection causes immune activation involves the intestinal tract. HIV infects immune cells the intestine soon after infection and damages their immune barrier. This damage lets bacteria cross into the bloodstream, leading to ongoing inflammation. Even when a person with HIV feels well, this chronic inflammation may affect the immune system. Researchers want to see if the antibiotic Rifaximin can reduce this inflammation. Rifaximin is designed to stay inside the digestive system, so it affects only bacteria in the intestines.
- To see if Rifaximin can reduce bacteria-related inflammation in people with HIV.
- Individuals at least 18 years of age who have HIV infection and are taking medications to treat it.
- Participants will be screened with a physical exam, blood test, and medical history.
- Participants will take either Rifaximin or a placebo for 4 weeks. They will have no medication for 4 to 6 weeks, and then take the other drug for 4 more weeks.
- During the study, participants will have frequent blood and urine tests. They will also provide stool samples. Liver and kidney function tests will be performed. HIV viral load (the amount of virus in the blood) will also be studied.
- Participants will have a final follow-up visit after an additional 4 weeks.
- Two additional tests are optional for study participants:
- Two blood draws: one on the third day after starting Rifaximin, and one on the third day after starting the placebo.
- Up to three colonoscopies of the lower intestine and biopsies of the intestine. These studies will collect samples of the intestinal tract to look at the effects of Rifaximin in the study.
Drug: Rifaximin/ Placebo
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
||A Double Blind Randomized Placebo Controlled Study Examining the Effects of a Non-Absorbable (Rifaximin) Antibiotic on the Chronic Immune Activation Observed In HIV-infected Subjects
Primary Outcome Measures:
- The primary objective is to compare the changes in sCD14 levels between the placebo and phases of the study [ Time Frame: End of Study Phase 2 ] [ Designated as safety issue: No ]
Secondary Outcome Measures:
- To compare the changes in HIV-1-RNA levels (using the single copy assay or the traditional HIV bDNA assay) between the placebo and the rifaximin phases of the study. [ Time Frame: End of Phase 2 ] [ Designated as safety issue: No ]
- To compare changes in soluble markers of inflammation between the placebo and rifaximin phases of the study. [ Time Frame: End of Phase 2 ] [ Designated as safety issue: No ]
- To compare the changes in cellular markers of IA (changes in the proportion ofCD4+ or CD8+ T cells that express HLA-DR and/or CD38) during the rifaximin phase of the study and compare it with the changes in cellular markers of activation during ... [ Time Frame: End of Phase 2 ] [ Designated as safety issue: No ]
| Estimated Enrollment:
| Study Start Date:
| Estimated Study Completion Date:
| Estimated Primary Completion Date:
||August 2017 (Final data collection date for primary outcome measure)
Experimental: HIV Infected Subjects
HIV infected subjects with viral suppression on ART.Double-blinded/placebo controlled trial with cross-overdesign.
Drug: Rifaximin/ Placebo
subject will receive either three capsules of rifaximin (183.3 mg each) by mouth twice daily (total 1100 mg Daily) or will receive three capsules of placebo by mouth twice daily.
|Ages Eligible for Study:
||18 Years and older
|Genders Eligible for Study:
|Accepts Healthy Volunteers:
- PARTICIPANT INCLUSION CRITERIA:
Patients who have agreed in the course of other research studies to have their records reviewed will have the following elements evaluated from their existing records: age, history of HIV infection, ART history and viral loads prior to informed consent, or else these elements will be assessed after informed consent. All blood draws to assess eligibility will be completed after obtaining informed consent. To participate in this study the criteria listed below will need to be met.
- Subjects must be 18 years of age or older.
- Able and willing to provide written informed consent
- Must have a history of documented HIV infection.
- HIV infection if not previously documented at host institutions will need to be documented by a plasma HIV RNA viral load, rapid HIV test or any other licensed ELISA test and confirmed by another test using a different method such as a rapid HIV test, Western Blot, HIV culture, HIV antigen, HIV pro-viral DNA at any time prior to study entry.
- ART- treated subjects who are virologically suppressed for greater than or equal to 3 years (1095 days). To meet this criteria all documented viral loads in the 3 years (1095 days) prior to the screening visit must be below the lower limit of detection [LLD] using FDA-approved standard assays (i.e. < 50 copies/mL) with the following clarification: In each of the three prior years, subjects experiencing a single blip [i.e. viral loads above the lower limit of detection, LLD] may be included provided they satisfy the following criteria: the blips are below 200 copies/ml, and the blip is surrounded (i.e the preceding and succeeding viral loads) by undetectable HIV-1 RNA level measurements. That is all viral loads must be below LLD EXCEPT for up to one blip . In any 12 month period.
- Viral RNA level < 50 c/ml at Screen 1.
- A minimum of 2 HIV-1 RNA levels that are below the lower limit of detection using standard assays will be required during the 12 month period prior to their screening visit. As assay characteristics across the sites can vary, LLD for the assay will be used to define whether or not a subject is suppressed.
- Stable dose of statin therapy for 6 months if receiving statin therapy.
- No known allergy or contraindication to the use of rifamycin compounds such as rifampin, rifabutin or rifaximin. .
- The effect of rifaximin on the developing human fetus are unknown, therefore subjects must be willing to use two methods of contraception (one of which must be a barrier method) during the study period. Adequate methods of birth control include: tubal ligation, hysterectomy, condoms (male or female) with or without a spermicide; diaphragm or cervical cap with spermicide; intrauterine device; any of the methods that require a prescription (such as contraceptive pills or patch, Norplant, Depo-Provera, and others) or a male partner who has previously undergone a vasectomy.
The following elements will be assessed with a blood draw and after obtaining informed consent.
- Absolute Neutrophil count (ANC) greater than or equal to 750/mm(3)
- Hemoglobingreater than or equal to 10.0 g/dL for women and Hemoglobin 11.0 g/dl for men
- Platelet count greater than or equal to 75,000/mm(3)
- Estimated Glomerular Filtration Rate (eGFR) > 60 mL/min, eGFR will be calculated using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation
- Confirmed serum glutamate pyruvate transaminase (SGPT)/serum glutamate oxaloacetate transferase (SGOT) less than or equal to 3 times the upper limit of normal (ULN)
- INR less than or equal to the ULN for the assay
- Negative urine pregnancy test of child bearing potential at randomization
- No evidence of active hepatitis B or hepatitis C (active hepatitis B will be defined as a positive hepatitis B surface antigen present on a single determination, whereas a positive result on hepatitis C RNA will be considered as evidence of active hepatitis C)
All routine laboratory testing used to determine safety will be completed within the 70 days prior to randomization.
- Known bleeding diathesis (for example a diagnosis of hemophilia or Von Willebrand disease)
- Active drug use or alcohol abuse/dependence, which in the opinion of the investigators will interfere with the patient s ability to participate in the study
- Serious illness requiring systemic treatment and/or hospitalization within 30 days of screening into the study
- Evidence of active opportunistic infections or neoplasms (excluding cutaneous basal cell carcinoma and squamous cell carcinoma) in the 6 months prior to randomization
- History of inflammatory bowel disease (Crohn s Disease, ulcerative colitis)
- Positive urine pregnancy test at screening (of child bearing potential).
- Current imprisonment
- Concurrent immunomodulatory agents, including systemic corticosteroids in the 12 weeks prior to randomization. Topical, nasal or inhaled corticosteroid use is allowed
- Concomitant use of probiotics except yogurt
- Chronic antibiotic use such as tetracyclines for acne
- Vaccinations within 6 weeks of randomization
- Concomitant use of anticoagulants (other than aspirin and NSAIDS) is an exclusion criterion for subjects opting in for the colonoscopy. Aspirin and NSAIDs will be discontinued per each institutions requirement before the procedure.
- Child-Pugh Class C disease
- A prior history of Clostridium difficile colitis
- Any condition that precludes the safe administration of conscious sedation for endoscopy (such as decompensated lung or heart disease) will not be able to participate in the colonoscopy aspect of the protocol.
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, see Learn About Clinical Studies.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01866826
|National Institutes of Health Clinical Center, 9000 Rockville Pike
|Bethesda, Maryland, United States, 20892 |
|Contact: For more information at the NIH Clinical Center contact Patient Recruitment and Public Liaison Office (PRPL) 800-411-1222 ext TTY8664111010 firstname.lastname@example.org |
|Walter Reed National Medical Center
|Bethesda, Maryland, United States, 20301 |
|University of Pittsburgh
|Pittsburgh, Pennsylvania, United States, 15213 |
University of Pittsburgh Division of Infectious Diseases
Walter Reed Navy MMC
||Frank Maldarelli, M.D.
||National Cancer Institute (NCI)
Kuller LH, Tracy R, Belloso W, De Wit S, Drummond F, Lane HC, Ledergerber B, Lundgren J, Neuhaus J, Nixon D, Paton NI, Neaton JD; INSIGHT SMART Study Group. Inflammatory and coagulation biomarkers and mortality in patients with HIV infection. PLoS Med. 2008 Oct 21;5(10):e203.
||National Institutes of Health Clinical Center (CC) ( National Cancer Institute (NCI) )
History of Changes
|Other Study ID Numbers:
|Study First Received:
||May 29, 2013
||September 16, 2014
||United States: Federal Government
Keywords provided by National Institutes of Health Clinical Center (CC):
Additional relevant MeSH terms:
ClinicalTrials.gov processed this record on November 20, 2014