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Mesalamine to Reduce T Cell Activation in HIV Infection

Primary Purpose

HIV Infections, Sexually Transmitted Diseases, Immune System Diseases

Status

Completed

Phase

Phase 4

Locations

United States

Study Type

Interventional

Intervention

Mesalamine (5-aminosalicylic acid, Apriso)

Placebo

About this trial

This is an interventional treatment trial for HIV Infections

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

HIV-1 infection, as documented by any licensed ELISA test kit and confirmed by Western blot at any time prior to study entry.
Stable antiretroviral therapy for at least 6 months.
Screening CD4+ T cell count below 350 cells/mm3
All available CD4+ T cell counts in the last year and at screening <350 cells/mm3
Screening plasma HIV RNA levels below level of detection (< 40 copies RNA/mL).
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.
>90% adherence to therapy within the preceding 30 days, as determined by self-report.
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:

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

Sites / Locations

University of California, San Francisco-San Francisco General Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Mesalamine

Placebo

Arm Description

Outcomes

Primary Outcome Measures

Log(10) Change in % Activated (CD38+HLA-DR+)CD8+ T Cells During the First 12 Weeks of Study

Secondary Outcome Measures

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

Full Information

NCT ID

NCT01090102

First Posted

March 17, 2010

Last Updated

August 8, 2014

Sponsor

University of California, San Francisco

Collaborators

California HIV/AIDS Research Program, Bausch Health Americas, Inc.

1. Study Identification

Unique Protocol Identification Number

NCT01090102

Brief Title

Mesalamine to Reduce T Cell Activation in HIV Infection

Official Title

Mesalamine to Reduce T Cell Activation in HIV Infection

Study Type

Interventional

2. Study Status

Record Verification Date

August 2014

Overall Recruitment Status

Completed

Study Start Date

June 2010 (undefined)

Primary Completion Date

December 2012 (Actual)

Study Completion Date

December 2012 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

University of California, San Francisco

Collaborators

California HIV/AIDS Research Program, Bausch Health Americas, Inc.

4. Oversight

5. Study Description

Brief Summary

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.

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

HIV Infections, Sexually Transmitted Diseases, Immune System Diseases, Lentivirus Infections, Acquired Immunodeficiency Syndrome

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 4

Interventional Study Model

Crossover Assignment

Masking

ParticipantInvestigator

Allocation

Randomized

Enrollment

33 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Mesalamine

Arm Type

Experimental

Arm Title

Placebo

Arm Type

Placebo Comparator

Intervention Type

Drug

Intervention Name(s)

Mesalamine (5-aminosalicylic acid, Apriso)

Intervention Description

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).

Intervention Type

Drug

Intervention Name(s)

Placebo

Intervention Description

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).

Primary Outcome Measure Information:

Title

Log(10) Change in % Activated (CD38+HLA-DR+)CD8+ T Cells During the First 12 Weeks of Study

Time Frame

Week 0, Week 12

Secondary Outcome Measure Information:

Title

Log(10) Change in % Activated (CD38+HLA-DR+)CD8+ T Cells After Treatment Crossover

Description

Log(10) change in the percentage of activated T cells during the second 12 weeks of the study

Time Frame

Week 12, Week 24

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: HIV-1 infection, as documented by any licensed ELISA test kit and confirmed by Western blot at any time prior to study entry. Stable antiretroviral therapy for at least 6 months. Screening CD4+ T cell count below 350 cells/mm3 All available CD4+ T cell counts in the last year and at screening <350 cells/mm3 Screening plasma HIV RNA levels below level of detection (< 40 copies RNA/mL). 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. >90% adherence to therapy within the preceding 30 days, as determined by self-report. 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: Patients who are intending to modify antiretroviral therapy in the next 24 weeks for any reason. Serious illness requiring hospitalization or parental antibiotics within preceding 3 months. Exposure to any immunomodulatory drug in the past 16 weeks. Active hepatitis C or hepatitis B which will require treatment in the subsequent 24 weeks. Screening absolute neutrophil count <1,000 cells/mm3, platelet count <50,000 cells/mm3, Hgb < 8mg/dL Pancreatitis or lipase greater than 2 times the upper limit of normal. Renal insufficiency with creatinine clearance less than 50 ml/min Elevated transaminases greater than 2.5 times the upper limit of normal. Evidence of decompensated cirrhosis, heart failure. Pregnant or breastfeeding women

Facility Information:

Facility Name

University of California, San Francisco-San Francisco General Hospital

City

San Francisco

State/Province

California

ZIP/Postal Code

94110

Country

United States

12. IPD Sharing Statement

Citations:

PubMed Identifier

25545673

Citation

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.

Results Reference

derived

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Mesalamine to Reduce T Cell Activation in HIV Infection

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