Lubiprostone as a Modulator of Gut Microbial Translocation in HIV With Incomplete CD4 Recovery on Antiretroviral Therapy
Condition: HIV
Intervention: Lubiprostone
Intervention description: Lubiprostone 24 mcg by mouth (PO) once-daily
Intervention MeSH terms: Lubiprostone
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 20.0
Sex: All
Minimum age: 18 Years
Maximum age: 65 Years
Healthy volunteers: No
Keywords: CD4+

Summary:

      The use of lubiprostone will decrease the levels of immune activation in HIV-infected
      subjects with incomplete CD4+ T-cell recovery with antiretroviral therapy (ART).

        -  Lubiprostone will decrease levels of translocated gut microbial products in HIV-infected
           subjects with incomplete CD4+ T-cell recovery with ART.

        -  The decrease in levels of translocated gut microbial products will be associated with a
           decline in the levels of immune activation in HIV-infected subjects with incomplete CD4+
           T-cell recovery with ART.
    

Eligibility criteria:

        Inclusion Criteria:

          -  HIV-1 infection, documented by any licensed rapid HIV test or HIV enzyme or
             chemiluminescence immunoassay (E/CIA) test kit at any time prior to study entry and
             confirmed by Western blot or a second antibody test by a method other than the initial
             rapid HIV and/or E/CIA, or by HIV-1 antigen, plasma HIV-1 RNA viral load.

          -  On tenofovir/emtricitabine/efavirenz single tablet combination therapy for at least 72
             weeks prior to study entry.

          -  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 72 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).

          -  Fasting laboratory values obtained within 45 days prior to entry as follows:

               -  Absolute neutrophil count (ANC) ≥ 1000/mm3

               -  Hemoglobin ≥ 10.0 g/dL

               -  Platelet count ≥ 50,000/mm3

               -  International normalized ratio (INR)

          -  Female subjects of reproductive potential (defined as girls who have reached menarche
             or women who have not been post-menopausal for at least 24 consecutive months; i.e.,
             those who have had menses within the preceding 24 months or have not undergone a
             sterilization procedure [hysterectomy, bilateral oophorectomy, bilateral tubal
             ligation, or bilateral salpingectomy]) 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 below while receiving protocol-specified
        treatment and for 4 weeks after stopping the treatment.

          -  If the female subject is not of reproductive potential (girls who have not reached
             menarche, women who have been post-menopausal for at least 24 consecutive months, or
             women who have undergone surgical sterilization, e.g., hysterectomy, bilateral
             oophorectomy, or bilateral tubal ligation or salpingectomy), she is eligible without
             requiring the use of a contraceptive. Self report is acceptable documentation of
             sterilization, other contraceptive methods, and menopause.

          -  Men and women age ≥ 18 and ≤ 65 years of age.

          -  Ability and willingness of subject or legally authorized representative to provide
             informed consent.

        Exclusion Criteria:

          -  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 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.

          -  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 (e.g., azathioprine, corticosteroids [physiologic replacement
                  doses are allowed], cyclosporine, mycophenolate, NSAIDs (nonsteroidal
                  anti-inflammatory drugs), sirolimus, sulfasalazine, tacrolimus)

               -  Immune modulators (e.g., cytokines [e.g., IL-2], granulocyte colony stimulating
                  factor, growth hormone, tumor necrosis factor antagonists, thalidomide)

               -  Antineoplastic agents

               -  Probiotics (defined as products that contain significant amounts of live
                  microorganisms and are ingested for specific health benefits, e.g., yogurt with
                  live and active cultures, Lactobacillus GG, Saccharomyces boulardii)

               -  Anticoagulants (e.g., warfarin and heparin)

          -  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.

          -  Participation on any HIV immunotherapy/therapeutic vaccination trials within 6 months
             prior to study entry.

          -  Active drug or alcohol use or dependence that, in the opinion of the site
             investigator, would interfere with adherence to study requirements.

          -  Breastfeeding.