Immune Activation and Drug Absorption in HIV-Infected Patients

This study is not yet open for participant recruitment.
Verified April 2013 by Drexel University
Sponsor:
Information provided by (Responsible Party):
Christopher Vinnard, Drexel University College of Medicine
ClinicalTrials.gov Identifier:
NCT01845298
First received: April 29, 2013
Last updated: May 1, 2013
Last verified: April 2013
  Purpose

The investigators' objective is to describe the variability of rifampicin absorption, markers of inflammation and gut damage, intestinal absorptive capacity, and intestinal permeability among HIV-infected volunteers. Rifampicin is the least well absorbed of the first-line anti-tuberculosis drugs. Rifampicin malabsorption is frequently observed in HIV-infected patients with active tuberculosis, but cannot be predicted by patient factors such as CD4+ T cell count, viral load, or the presence of diarrhea. The mechanisms for rifampicin malabsorption in HIV-infected patients are unknown. An understanding of mechanisms for rifampicin malabsorption could eventually lead to new therapeutic targets, with the ultimate goal of improving HIV/tuberculosis treatment outcomes.


Condition Intervention
HIV Infection
Drug: Rifampicin 600 mg

Study Type: Interventional
Study Design: Endpoint Classification: Pharmacokinetics Study
Intervention Model: Single Group Assignment
Masking: Open Label

Resource links provided by NLM:


Further study details as provided by Drexel University:

Primary Outcome Measures:
  • Rifampicin Absorption (Ka) [ Time Frame: Baseline ] [ Designated as safety issue: No ]
    The investigators will perform a pharmacokinetic study to assess rifampicin absorption among study subjects. Pharmacokinetic modeling will be used to assess the absorption rate constant (Ka) for each subject.


Estimated Enrollment: 10
Study Start Date: July 2013
Estimated Primary Completion Date: December 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: HIV-infected subjects
HIV-infected subjects who have not yet initiated highly active antiretroviral therapy (HAART). All enrolled subjects will receive a single dose of rifampicin 600 mg.
Drug: Rifampicin 600 mg
The investigators will administer a single dose of rifampicin 600 mg to study subjects in order to conduct a pharmacokinetic study of rifampicin absorption.

  Eligibility

Ages Eligible for Study:   21 Years to 45 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • HIV-infected males and females, between the ages of 21 and 45 years.
  • Naïve to antiretroviral therapy
  • T cell count greater than 350 cells/mm3
  • Body Mass Index (BMI) greater or equal to 19 and less than or equal to 33.
  • Weight greater than 60 kilograms.
  • Ability and willingness to provide informed consent.
  • Ability to swallow oral medications

Exclusion Criteria:

  • Breastfeeding.
  • Allergy or sensitivity to rifampicin.
  • Prior history of documented active tuberculosis infection.
  • Receipt of any investigational therapy, chemotherapy, or immune modulatory agents within 42 days prior to study entry.
  • The following laboratory values obtained within 42 days prior to study entry:

Hemoglobin < 12.0 g/dL; Females: Hemoglobin < 11.0 g/dL Platelet count < 100,000/mm3 AST, ALT, and bilirubin > 5x ULN An estimated creatinine clearance < 80 mL/min based on the Cockroft-Gault equation

  • Positive blood test for latent tuberculosis infection (T-SPOT)
  • Female participants of reproductive potential must have a negative serum or urine pregnancy test performed with 28 days prior to study entry.

"Female participants of reproductive potential" is defined as women who have reached menarche or who have not been post-menopausal for at least 24 consecutive months (i.e. who have had menses within the preceding 24 months) or who have not undergone surgical sterilization (e.g. hysterectomy, or bilateral oophorectomy or salpingectomy).

  • Female participants of reproductive potential that are using oral contraceptive pills (OCPs) must be willing to use barrier precautions for contraception for at least 7 days following each study visit.
  • Use of any of the following prescription medications within 30 days prior to study entry, which may have drug-drug interactions with rifampicin, including (but not limited to):

    • Anti-coagulants (warfarin)
    • Cardiac drugs (digoxin, quinidine, verapamil, nifedipine, metoprolol, atenolol, carvedilol)
    • Hypoglycemics (rosiglitazone, pioglitazone, glipizide, repaglinide)
    • Proton pump inhibitors (omeprazole, esomeprazole,
    • Immune modulators (tacrolimus, cyclosporine)
    • Corticosteroids (dexamethasone, prednisone, hydrocortisone)
    • H2 blockers (ranitidine, cimetidine)
    • HMG CoA reductase inhibitors (atorvastatin, pravastatin, simvastatin)
    • Benzodiazepines (alprazolam, diazepam, midazolam, triazolam)
    • CNS-acting drugs (amitriptyline, buproprion, clozapine, phenytoin)
  • Evidence of current ongoing tobacco use, illicit drug use, or average alcohol use of greater than 2 drinks per day.
  • Any illness that, in the opinion of the study investigator, might confound the results of the study, or pose an additional risk to the subject by his or her participation in the study.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01845298

Contacts
Contact: Christopher Vinnard, MD 215 762 6555 christopher.vinnard@drexelmed.edu

Locations
United States, Pennsylvania
Drexel University College of Medicine Not yet recruiting
Philadelphia, Pennsylvania, United States, 19102
Contact: Christopher Vinnard, MD    215-762-6555    christopher.vinnard@drexelmed.edu   
Principal Investigator: Christopher Vinnard, MD         
Sponsors and Collaborators
Christopher Vinnard
  More Information

Publications:
Responsible Party: Christopher Vinnard, Assistant Professor of Medicine, Drexel University College of Medicine
ClinicalTrials.gov Identifier: NCT01845298     History of Changes
Other Study ID Numbers: TMC114HIV4076
Study First Received: April 29, 2013
Last Updated: May 1, 2013
Health Authority: United States: Institutional Review Board

Additional relevant MeSH terms:
HIV Infections
Acquired Immunodeficiency Syndrome
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Slow Virus Diseases
Rifampin
Antibiotics, Antitubercular
Anti-Bacterial Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Antitubercular Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Leprostatic Agents
Nucleic Acid Synthesis Inhibitors

ClinicalTrials.gov processed this record on April 17, 2014