CCRC: A Pilot Project of Virologic, Pharmacologic and Immunologic Correlates of Gastrointestinal-Associated Lymphoid Tissue Immune Reconstitution Following Raltegravir Therapy

This study has been completed.
Sponsor:
Information provided by:
University of California, Davis
ClinicalTrials.gov Identifier:
NCT00661960
First received: April 16, 2008
Last updated: August 2, 2011
Last verified: August 2011

April 16, 2008
August 2, 2011
March 2008
December 2010   (final data collection date for primary outcome measure)
To correlate the increase in frequency of CD3+/CD4+ cells per cubic millimeter at the effector sites in the duodenal tissues obtained from volunteers to the antiretroviral therapy regimen over time. [ Time Frame: nine months ] [ Designated as safety issue: No ]
Same as current
Complete list of historical versions of study NCT00661960 on ClinicalTrials.gov Archive Site
  • To measure the trough plasma and tissue drug levels in volunteers at the time of the upper endoscopy [ Time Frame: nine months ] [ Designated as safety issue: No ]
  • To correlate the level of HIV RNA per gram of duodenal tissue versus plasma HIV load and drug regimen received [ Time Frame: nine months ] [ Designated as safety issue: No ]
  • To measure the change in GALT CD4+ and CD8+T-cell subpopulations (naive versus memory) in volunteers receiving raltegravir versus NNRTI [ Time Frame: nine months ] [ Designated as safety issue: No ]
  • To assess GALT immune function and activation in volunteers receiving raltegravir versus NNRTI [ Time Frame: nine months ] [ Designated as safety issue: No ]
  • To explore whether the treatment regimen correlates with the changes in CD3+/CD4+ T-cell numbers [ Time Frame: nine months ] [ Designated as safety issue: No ]
  • To compare the level of immune reconstitution with respect to absolute numbers of CD4+ T-cells, the relative proportion of T-cell subpopulations in the tissue, and immune activation to a cohort of normal controls [ Time Frame: nine months ] [ Designated as safety issue: No ]
Same as current
Not Provided
Not Provided
 
CCRC: A Pilot Project of Virologic, Pharmacologic and Immunologic Correlates of Gastrointestinal-Associated Lymphoid Tissue Immune Reconstitution Following Raltegravir Therapy
CCRC: A Pilot Project of Virologic, Pharmacologic and Immunologic Correlates of Gastrointestinal-Associated Lymphoid Tissue Immune Reconstitution Following Raltegravir Therapy

This research is being done to study how the immune system in the small intestine improves after taking antiretroviral (anti-HIV) medications. The main purpose is to measure the increase in the numbers of immune cells in the intestine to see if one type of HIV medication gives different results than other types of HIV medications.

While the world-wide AIDS epidemic continues to impact millions of individuals, effective anti-HIV medications have substantially reduced morbidity and mortality for those patients able to adhere to combination regimens. Despite improved survival, durable virologic suppression, and increases in peripheral CD4+T-cell counts in patients receiving potent antiretroviral therapy (ART), immune reconstitution remains incomplete as measured by a number of additional surrogate markers. Perhaps critically important among areas of apparent incomplete immune recovery is the gastrointestinal-associated lymphoid tissue (GALT), where CD4+T-cells repopulate very slowly, if at all. Raltegravir is a new ART agent from a novel class of HIV inhibitors, integrase inhibitors, that results in rapid suppression of HIV and recovery of peripheral CD4+T-cells. This project proposes to examine whether volunteers receiving raltegravir recover GALT immune cells more completely than those taking comparator ART.

Interventional
Not Provided
Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
  • HIV Infections
  • AIDS
  • Procedure: Upper Endoscopy and biopsies
    5 HIV-Negative volunteers will only undergo this single procedure - A gastroenterologist (specialist in intestinal disease) will pass a flexible endoscope tube connected to a video camera, into the stomach and small intestine, will examine these areas, and will biopsy (take small pieces of tissue--about the size of a grain of rice) these areas.
  • Drug: raltegravir
    400mg tablet twice daily by mouth for nine months
    Other Name: Isentress
  • Drug: efavirenz
    600mg capsule once daily by mouth without regard to food
    Other Name: Sustiva
  • No Intervention: 1
    HIV Negative volunteers
    Intervention: Procedure: Upper Endoscopy and biopsies
  • Active Comparator: 2
    HIV-Positive volunteers taking raltegravir in combination with two other nucleoside reverse transcriptase inhibitors (NRTI) medications
    Intervention: Drug: raltegravir
  • Active Comparator: 3
    HIV-Positive volunteers taking efavirenz or any other non-nucleoside reverse transcriptase inhibitors (NNRTI) in combination with two other nucleoside reverse transcriptase inhibitor (NRTI) medications
    Intervention: Drug: efavirenz
Ellis CL, Ma ZM, Mann SK, Li CS, Wu J, Knight TH, Yotter T, Hayes TL, Maniar AH, Troia-Cancio PV, Overman HA, Torok NJ, Albanese A, Rutledge JC, Miller CJ, Pollard RB, Asmuth DM. Molecular characterization of stool microbiota in HIV-infected subjects by panbacterial and order-level 16S ribosomal DNA (rDNA) quantification and correlations with immune activation. J Acquir Immune Defic Syndr. 2011 Aug 15;57(5):363-70. doi: 10.1097/QAI.0b013e31821a603c.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
25
March 2011
December 2010   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • willing to sign consent form
  • no known GI pathology
  • no anticipated antiretroviral therapy adjustments or changes
  • males & females between the ages of 18 & 50 years
  • no active opportunistic infections (OI) or therapy for OI within 30 days of entry
  • can be on secondary prophylaxis with a history of AIDS defining illness
  • per standard of care requirements, all females of child-bearing potential must agree to use barrier methods to prevent pregnancy or be abstinent from activity while on study

Exclusion Criteria:

  • abnormal coagulation parameters (PT > or equal to 1.2 ULN)
  • thrombocytopenia (platelet count < 50,000 within 6 weeks)
  • contra-indications to upper endoscopy or conscious sedation
  • anemia (> or equal to grade 1)
  • aspirin, ibuprofen, warfarin or other agents that interfere with the coagulation cascade are prohibited within 1 week of endoscopy
Both
18 Years to 50 Years
Yes
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00661960
200715792
No
David M. Asmuth, M.D. / Principal Investigator, University of California, Davis
University of California, Davis
Not Provided
Principal Investigator: David M. Asmuth, M.D. University of California, Davis
University of California, Davis
August 2011

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP