Mesalamine to Reduce T Cell Activation in HIV Infection

This study has been completed.
Sponsor:
Collaborators:
California HIV/AIDS Research Program
Salix Pharmaceuticals
Information provided by (Responsible Party):
University of California, San Francisco
ClinicalTrials.gov Identifier:
NCT01090102
First received: March 17, 2010
Last updated: August 8, 2014
Last verified: August 2014
  Purpose

The objective of this study is to determine whether 12 weeks of mesalamine therapy added to a standard HIV treatment decreases systemic immune activation and inflammation in HIV-infected patients, possibly resulting in better recovery of the immune system. The study hypothesis is that decreasing inflammation directly in the gut may decrease both of these potential causes of chronic inflammation, potentially resulting in an immunologic benefit.


Condition Intervention Phase
HIV Infections
Sexually Transmitted Diseases
Immune System Diseases
Lentivirus Infections
Acquired Immunodeficiency Syndrome
Drug: Mesalamine (5-aminosalicylic acid, Apriso)
Drug: Placebo
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: Mesalamine to Reduce T Cell Activation in HIV Infection

Resource links provided by NLM:


Further study details as provided by University of California, San Francisco:

Primary Outcome Measures:
  • Log(10) Change in % Activated (CD38+HLA-DR+)CD8+ T Cells During the First 12 Weeks of Study [ Time Frame: Week 0, Week 12 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Log(10) Change in % Activated (CD38+HLA-DR+)CD8+ T Cells After Treatment Crossover [ Time Frame: Week 12, Week 24 ] [ Designated as safety issue: No ]
    Log(10) change in the percentage of activated T cells during the second 12 weeks of the study


Enrollment: 33
Study Start Date: June 2010
Study Completion Date: December 2012
Primary Completion Date: December 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Mesalamine Drug: Mesalamine (5-aminosalicylic acid, Apriso)

Four mesalamine capsules once daily (1.5 gram/day) for the first 12 weeks, PO(by mouth).

Four placebo capsules once daily (1.5g/d) for another 12 weeks, PO (by mouth).

Placebo Comparator: Placebo Drug: Placebo

Four placebo capsules once daily (1.5g/d) for the first 12 weeks, PO (by mouth).

Four mesalamine capsules once daily (1.5g/d) for another 12 weeks, PO (by mouth).


Detailed Description:

While most HIV-infected patients can now achieve nearly complete viral suppression on currently available HIV medications, they still have at least a 10-year shorter life expectancy than the general population and are at higher risk for diseases associated with accelerated aging including cardiovascular disease and non-AIDS-defining cancers. Persistent inflammation and immune activation are believed to drive this increased risk. Despite suppression of viral replication in peripheral blood by effective HIV medications, HIV may continue to be expressed at low levels by T cells in the lining of the gut and may also result in translocation of bacterial products across the lining of the gut, driving persistent inflammation. We believe that decreasing inflammation directly in the gut may decrease both of these potential causes of chronic inflammation, potentially resulting in an immunologic benefit. Mesalamine is an oral anti-inflammatory drug used to treat patients with inflammatory bowel disease, acts locally on the gut tissue to decrease inflammation, and is associated with very few side effects. If mesalamine therapy reduces immune activation and inflammation in our study, it would prompt larger studies to see if mesalamine decreases clinical outcomes like cardiovascular disease, cancer, and mortality in this setting.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. HIV-1 infection, as documented by any licensed ELISA test kit and confirmed by Western blot at any time prior to study entry.
  2. Stable antiretroviral therapy for at least 6 months.
  3. Screening CD4+ T cell count below 350 cells/mm3
  4. All available CD4+ T cell counts in the last year and at screening <350 cells/mm3
  5. Screening plasma HIV RNA levels below level of detection (< 40 copies RNA/mL).
  6. All available plasma HIV RNA levels within past year below the level of detection. Isolated detectable values < 500 c/ml are allowed if HIV RNA levels before and after this time point are undetectable.
  7. >90% adherence to therapy within the preceding 30 days, as determined by self-report.
  8. Both male and female subjects are eligible. Females of childbearing potential must have negative pregnancy test at screening and agree to use a double-barrier method of contraception during the study.

Exclusion Criteria:

  1. Patients who are intending to modify antiretroviral therapy in the next 24 weeks for any reason.
  2. Serious illness requiring hospitalization or parental antibiotics within preceding 3 months.
  3. Exposure to any immunomodulatory drug in the past 16 weeks.
  4. Active hepatitis C or hepatitis B which will require treatment in the subsequent 24 weeks.
  5. Screening absolute neutrophil count <1,000 cells/mm3, platelet count <50,000 cells/mm3, Hgb < 8mg/dL
  6. Pancreatitis or lipase greater than 2 times the upper limit of normal.
  7. Renal insufficiency with creatinine clearance less than 50 ml/min
  8. Elevated transaminases greater than 2.5 times the upper limit of normal.
  9. Evidence of decompensated cirrhosis, heart failure.
  10. Pregnant or breastfeeding women
  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: NCT01090102

Locations
United States, California
University of California, San Francisco-San Francisco General Hospital
San Francisco, California, United States, 94110
Sponsors and Collaborators
University of California, San Francisco
California HIV/AIDS Research Program
Salix Pharmaceuticals
  More Information

No publications provided

Responsible Party: University of California, San Francisco
ClinicalTrials.gov Identifier: NCT01090102     History of Changes
Other Study ID Numbers: 164320
Study First Received: March 17, 2010
Results First Received: May 20, 2014
Last Updated: August 8, 2014
Health Authority: United States: Institutional Review Board

Additional relevant MeSH terms:
Acquired Immunodeficiency Syndrome
HIV Infections
Immunologic Deficiency Syndromes
Immune System Diseases
Sexually Transmitted Diseases
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Slow Virus Diseases
Infection
Genital Diseases, Male
Genital Diseases, Female
Aminosalicylic Acid
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
Anti-Inflammatory Agents
Antirheumatic Agents
Central Nervous System Agents

ClinicalTrials.gov processed this record on August 26, 2014