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Protocol Details

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

This study is NOT currently recruiting participants.

Summary | Eligibility | Citations | Contacts

Summary

Number

13-I-0062

Sponsoring Institute

National Institute of Allergy and Infectious Diseases (NIAID)

Recruitment Detail

Type: Completed Study; data analyses ongoing
Gender: Male & Female
Min Age: 18
Max Age: 65

Referral Letter Required

No

Population Exclusion(s)

Children;
Pregnant Women and Fetuses

Special Instructions

Currently Not Provided

Keywords

HIV

Recruitment Keyword(s)

None

Condition(s)

HIV

Investigational Drug(s)

None

Investigational Device(s)

None

Intervention(s)

Drug: Rifaximin
Drug: Placebo

Supporting Site

National Institute of Allergy and Infectious DiseasesUniversity of Pittsburgh Division of Infectious DiseasesWalter Reed Navy MMC

Background:

- 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.

Objectives:

- To see if Rifaximin can reduce bacteria-related inflammation in people with HIV.

Eligibility:

- Individuals at least 18 years of age who have HIV infection and are taking medications to treat it.

Design:

- 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.

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Eligibility

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.

1. Subjects must be 18 years of age or older.

2. Able and willing to provide written informed consent

3. Must have a history of documented HIV infection.

4. 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.

5. 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.

6. Viral RNA level < 50 c/ml at Screen 1.

7. 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.

8. Stable dose of statin therapy for 6 months if receiving statin therapy.

9. No known allergy or contraindication to the use of rifamycin compounds such as rifampin, rifabutin or rifaximin. .

10. 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.

1. Absolute Neutrophil count (ANC) greater than or equal to 750/mm(3)

2. Hemoglobingreater than or equal to 10.0 g/dL for women and Hemoglobin 11.0 g/dl for men

3. Platelet count greater than or equal to 75,000/mm(3)

4. Estimated Glomerular Filtration Rate (eGFR) >60 mL/min, eGFR will be calculated using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation

5. Confirmed serum glutamate pyruvate transaminase (SGPT)/serum glutamate oxaloacetate transferase (SGOT) less than or equal to 3 times the upper limit of normal (ULN)

6. INR less than or equal to the ULN for the assay

7. Negative urine pregnancy test of child bearing potential at randomization

8. 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.

EXCLUSION CRITERIA:

1. Known bleeding diathesis (for example a diagnosis of hemophilia or Von Willebrand disease)

2. 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

3. Serious illness requiring systemic treatment and/or hospitalization within 30 days of screening into the study

4. Evidence of active opportunistic infections or neoplasms (excluding cutaneous basal cell carcinoma and squamous cell carcinoma) in the 6 months prior to randomization

5. History of inflammatory bowel disease (Crohn s Disease, ulcerative colitis)

6. Positive urine pregnancy test at screening (of child bearing potential).

7. Breastfeeding

8. Current imprisonment

9. Concurrent immunomodulatory agents, including systemic corticosteroids in the 12 weeks prior to randomization. Topical, nasal or inhaled corticosteroid use is allowed

10. Concomitant use of probiotics except yogurt

11. Chronic antibiotic use such as tetracyclines for acne

12. Vaccinations within 6 weeks of randomization

13. 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.

14. Child-Pugh Class C disease

15. A prior history of Clostridium difficile colitis

16. 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.


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Citations:

Deeks SG. Immune dysfunction, inflammation, and accelerated aging in patients on antiretroviral therapy. Top HIV Med. 2009 Sep-Oct;17(4):118-23.

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.

Hunt PW, Martin JN, Sinclair E, Bredt B, Hagos E, Lampiris H, Deeks SG. T cell activation is associated with lower CD4+ T cell gains in human immunodeficiency virus-infected patients with sustained viral suppression during antiretroviral therapy. J Infect Dis. 2003 May 15;187(10):1534-43. Epub 2003 Apr 23.

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Contacts:

Principal Investigator

Referral Contact

For more information:

Frank Maldarelli, M.D.
National Cancer Institute (NCI)
BG 10 RM 2B36A
10 CENTER DR
BETHESDA MD 20814
(240) 760-6082
fmalli@mail.nih.gov

Jennifer M. Bell
National Cancer Institute (NCI)
National Institutes of Health
Building 10
Room 2B36A
10 Center Drive
Bethesda, Maryland 20892
(240) 858-3187
jennifer.bell@nih.gov

Office of Patient Recruitment
National Institutes of Health Clinical Center (CC)
Building 61, 10 Cloister Court
Bethesda, Maryland 20892
Toll Free: 1-800-411-1222
Local Phone: 301-451-4383
TTY: 1-866-411-1010
PRPL@cc.nih.gov

Clinical Trials Number:

NCT01866826

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