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

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 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:

MedlinePlus related topics: HIV/AIDS

Drug Information available for: Aminosalicylic Acid

U.S. FDA Resources

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 (Adult)
Sexes 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

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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

National Institute of Allergy and Infectious Diseases (NIAID)

Investigators


Principal Investigator:	Peter A. Anton, MD	University of California, Los Angeles

More Information


ClinicalTrials.gov Identifier:	NCT00069498 History of Changes
Other Study ID Numbers:	K24AI001610-03 ( US NIH Grant/Contract Award Number )
Study First Received:	September 26, 2003
Last Updated:	May 24, 2007

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 Lentivirus Infections Retroviridae Infections RNA Virus Infections Virus Diseases Sexually Transmitted Diseases, Viral Sexually Transmitted Diseases Immunologic Deficiency Syndromes Immune System Diseases Mesalamine Anti-Inflammatory Agents	Aminosalicylic Acid Anti-Inflammatory Agents, Non-Steroidal Analgesics, Non-Narcotic Analgesics Sensory System Agents Peripheral Nervous System Agents Physiological Effects of Drugs Antirheumatic Agents Antitubercular Agents Anti-Bacterial Agents Anti-Infective Agents

ClinicalTrials.gov processed this record on June 28, 2017