Mesalamine to Reduce T Cell Activation in HIV Infection

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.

Study Overview

• Status: Completed
• Conditions: HIV Infections; Acquired Immunodeficiency Syndrome; Sexually Transmitted Diseases; Lentivirus Infections; Immune System Diseases
• Intervention / Treatment: Drug: Mesalamine (5-aminosalicylic acid, Apriso); Drug: Placebo

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.

• Study Type: Interventional
• Enrollment (Actual): 33
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • California
    • San Francisco, California, United States, 94110
      • University of California, San Francisco-San Francisco General Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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).
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).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Log(10) Change in % Activated (CD38+HLA-DR+)CD8+ T Cells During the First 12 Weeks of Study	Week 0, Week 12

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Log(10) Change in % Activated (CD38+HLA-DR+)CD8+ T Cells After Treatment Crossover	Log(10) change in the percentage of activated T cells during the second 12 weeks of the study	Week 12, Week 24

Collaborators and Investigators

• Sponsor: University of California, San Francisco
• Collaborators: Bausch Health Americas, Inc.; California HIV/AIDS Research Program

Publications and helpful links

General Publications

• Somsouk M, Dunham RM, Cohen M, Albright R, Abdel-Mohsen M, Liegler T, Lifson J, Piatak M, Gorelick R, Huang Y, Wu Y, Hsue PY, Martin JN, Deeks SG, McCune JM, Hunt PW. The immunologic effects of mesalamine in treated HIV-infected individuals with incomplete CD4+ T cell recovery: a randomized crossover trial. PLoS One. 2014 Dec 29;9(12):e116306. doi: 10.1371/journal.pone.0116306. eCollection 2014.

Study record dates

Study Major Dates

• Study Start: June 1, 2010
• Primary Completion (Actual): December 1, 2012
• Study Completion (Actual): December 1, 2012

Study Registration Dates

• First Submitted: March 17, 2010
• First Submitted That Met QC Criteria: March 18, 2010
• First Posted (Estimate): March 19, 2010

Study Record Updates

• Last Update Posted (Estimate): August 13, 2014
• Last Update Submitted That Met QC Criteria: August 8, 2014
• Last Verified: August 1, 2014

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; RNA Virus Infections; Virus Diseases; Blood-Borne Infections; Sexually Transmitted Diseases, Viral; Retroviridae Infections; Disease Attributes; Slow Virus Diseases; HIV Infections; Infections; Communicable Diseases; Acquired Immunodeficiency Syndrome; Immunologic Deficiency Syndromes; Sexually Transmitted Diseases; Immune System Diseases; Lentivirus Infections; Physiological Effects of Drugs; Anti-Infective Agents; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Anti-Bacterial Agents; Antitubercular Agents; Mesalamine; Aminosalicylic Acid
• Other Study ID Numbers: 164320