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

Sponsor:	University of California, Davis
Information provided by:	University of California, Davis
ClinicalTrials.gov Identifier:	NCT00661960

Purpose

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.

Condition	Intervention
HIV Infections AIDS	Procedure: Upper Endoscopy and biopsies Drug: raltegravir Drug: efavirenz

Study Type:	Interventional
Study Design:	Treatment, Randomized, Open Label, Active Control, Parallel Assignment, Efficacy Study
Official Title:	CCRC: A Pilot Project of Virologic, Pharmacologic and Immunologic Correlates of Gastrointestinal-Associated Lymphoid Tissue Immune Reconstitution Following Raltegravir Therapy

Resource links provided by NLM:

MedlinePlus related topics: AIDS Endoscopy

Drug Information available for: Efavirenz Raltegravir

U.S. FDA Resources

Further study details as provided by University of California, Davis:

Primary Outcome Measures:

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 ]

Secondary Outcome Measures:

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 ]

Estimated Enrollment:	25
Study Start Date:	March 2008
Estimated Study Completion Date:	June 2009
Estimated Primary Completion Date:	December 2008 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
1: No Intervention HIV Negative volunteers	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.
2: Active Comparator HIV-Positive volunteers taking raltegravir in combination with two other nucleoside reverse transcriptase inhibitors (NRTI) medications	Drug: raltegravir 400mg tablet twice daily by mouth for nine months
3: Active Comparator 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	Drug: efavirenz 600mg capsule once daily by mouth without regard to food

Detailed Description:

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.

Eligibility

Ages Eligible for Study:	18 Years to 50 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	Yes

Criteria

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00661960

Contacts

Contact: Tammy Yotter, B.S.R.N.	916-914-6261	tammy.yotter@ucdmc.ucdavis.edu
Contact: David M. Asmuth, M.D.	916-734-3742	david.asmuth@ucdmc.ucdavis.edu

Locations

United States, California
CARES Clinic	Recruiting
Sacramento, California, United States, 95814
Contact: Tammy Yotter, B.S.R.N. 916-914-6261 tammy.yotter@ucdmc.ucdavis.edu

Sponsors and Collaborators

University of California, Davis

Investigators

Principal Investigator:

David M. Asmuth, M.D.

University of California, Davis

More Information

No publications provided

Responsible Party:	University of California, Davis ( David M. Asmuth, M.D. / Principal Investigator )
Study ID Numbers:	200715792
Study First Received:	April 16, 2008
Last Updated:	May 8, 2008
ClinicalTrials.gov Identifier:	NCT00661960 History of Changes
Health Authority:	United States: Institutional Review Board

Keywords provided by University of California, Davis:

HIV Positive
AIDS
Antiretroviral Therapy

Gastrointestinal-Associated Lymphoid Tissue
Immune Reconstitution
treatment experienced

Additional relevant MeSH terms:

Anti-Infective Agents
Efavirenz
RNA Virus Infections
Sexually Transmitted Diseases, Viral
Anti-HIV Agents
Slow Virus Diseases
Molecular Mechanisms of Pharmacological Action
Immune System Diseases
Acquired Immunodeficiency Syndrome
Enzyme Inhibitors
Infection
Antiviral Agents

Pharmacologic Actions
Immunologic Deficiency Syndromes
Reverse Transcriptase Inhibitors
Virus Diseases
Anti-Retroviral Agents
HIV Infections
Therapeutic Uses
Sexually Transmitted Diseases
Lentivirus Infections
Retroviridae Infections
Nucleic Acid Synthesis Inhibitors

ClinicalTrials.gov processed this record on February 08, 2010