Effect of an Anti-Inflammatory Drug on Gut Mucosa in HIV Infected Patients

This study has been completed.
Sponsor:
Information provided by:
National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:
NCT00069498
First received: September 26, 2003
Last updated: May 24, 2007
Last verified: July 2006
  Purpose

The lining of the gastrointestinal tract contains specialized lymphoid tissue that is part of the immune system. Like other parts of the immune system, HIV attacks this lymphoid tissue. This study will evaluate the effect of an anti-inflammatory drug on the lymphoid tissue in the gastrointestinal tracts of people with HIV.


Condition Intervention Phase
HIV Infections
Drug: 5-aminosalicylic acid
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Factorial Assignment
Masking: Double-Blind
Primary Purpose: Treatment
Official Title: Impact of Co-Receptor and HIV Viral Burden on Gut Mucosa

Resource links provided by NLM:


Further study details as provided by National Institute of Allergy and Infectious Diseases (NIAID):

Primary Outcome Measures:
  • Safety of 4.8 g/day 5-ASA in HIV infected patients with detectable viral load

Secondary Outcome Measures:
  • Time/trend decrease in mucosal viral RNA load and plasma viral RNA load, compared to placebo
  • reduction in cellular infiltration in treated patients versus those taking placebo
  • change in inflammation, as measured by tissue destruction
  • reduction in soluble inflammation (RANTES), CCR5 expression, and cellular infiltration of CD8
  • changes in certain activation markers in gut

Estimated Enrollment: 14
Study Start Date: October 1999
Detailed Description:

The gastrointestinal tract is the body’s largest lymphoid organ. Because it contains significant numbers of activated memory T lymphocytes, it is a prime site for HIV infection and amplification. Mucosal T cells are extremely vulnerable to HIV infection due, in part, to a marked increase in CCR5 co-receptors. Understanding the impact of HIV on the gastrointestinal-associated lymphoid tissue (GALT) is essential and may provide insight into the profound drop in mucosal lymphocytes during early infection, persistence of tissue viral replication in the setting of undetectable plasma viral activity, and compartmentalization of HIV.

Pre-clinical studies have demonstrated that the mucosal compartment in HIV uninfected individuals is characterized by features which enhance vulnerability to HIV infection compared to blood. Once infected, the mucosal response to HIV is inflammation. This study will further evaluate the inflammatory response of mucosal tissue to HIV by examining the effect of the anti-inflammatory drug 5-aminosalicylic acid (5-ASA) on the gut mucosa.

Participants in this study will be randomly assigned to receive either 5-ASA or placebo. Participants will be enrolled in the study for 8 weeks; participants may then elect to continue on 5-ASA for an additional 16 weeks. Participants will have four screening visits in the month prior to beginning the study and four study visits during the 8-week study. Assessments will include medical interviews and physical exams, sigmoidoscopy with mucosal biopsy, and blood tests.

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria

  • HIV infected
  • Stable plasma viral load between 500 and 100,000 copies/ml for 3 months prior to study entry
  • Stable antiretroviral therapy for at least 3 months prior to study entry
  • CD4 cell count greater than or equal to 200 cells/mm3
  • Mucosal viral RNA greater than or equal to 100 copies/microg total RNA within 2 weeks of study entry

Exclusion Criteria

  • Allergy or intolerance to salicylates
  • Gastrointestinal tract infection causing diarrhea or colonic inflammation
  • Renal or hepatic disease
  • Current opportunistic infection
  • History of extensive small bowel resection (greater than 1/2 the length of the small intestine)
  • History of intestinal mucosal disease (except HIV)
  • Chronic, regular use of aspirin and/or anti-inflammatory agents within 7 weeks prior to study entry
  • Oral, topical, or rectal steroids or 5-ASA within 3 months prior to study entry
  • Certain laboratory abnormalities
  • Significant neuropsychiatric symptoms that in the opinion of the study official could impact the conduct or outcome of the study
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00069498

Locations
United States, California
David Geffen School of Medicine at UCLA
Los Angeles, California, United States, 90095
Sponsors and Collaborators
Investigators
Principal Investigator: Peter A. Anton, MD University of California, Los Angeles
  More Information

No publications provided

ClinicalTrials.gov Identifier: NCT00069498     History of Changes
Other Study ID Numbers: K24AI01610-03, K24 AI01610-03
Study First Received: September 26, 2003
Last Updated: May 24, 2007
Health Authority: United States: Federal Government

Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):
Mucosa
Inflammation
Tissue Viral Load
Anti-inflammatory
HIV-related diarrhea
Mucosal Inflammation
Treatment Experienced

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
Aminosalicylic Acid
Anti-Inflammatory Agents
Mesalamine
Antitubercular Agents
Anti-Bacterial Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Antirheumatic Agents
Central Nervous System Agents

ClinicalTrials.gov processed this record on April 17, 2014