Acquired Immunodeficiency Syndrome, HIV Infections, Immune System Diseases, Lentivirus Infections, Sexually Transmitted Diseases
Conditions
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.
Interventions
DRUGMesalamine (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).
DRUGPlacebo
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).
Sponsors
California HIV/AIDS Research Program
Bausch Health Americas, Inc.
University of California, San Francisco
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| 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
| Measure | Time frame | Description |
|---|---|---|
| Log(10) Change in % Activated (CD38+HLA-DR+)CD8+ T Cells After Treatment Crossover | Week 12, Week 24 | Log(10) change in the percentage of activated T cells during the second 12 weeks of the study |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Mesalamine Then Placebo Mesalamine (5-aminosalicylic acid, Apriso): Four mesalamine capsules once daily (1.5 gram/day) for the first 12 weeks, PO(by mouth), followed by Four placebo capsules once daily (1.5g/d) for another 12 weeks, PO (by mouth). | 15 |
| Placebo Then Mesalamine Placebo: Four placebo capsules once daily (1.5g/d) for the first 12 weeks, PO (by mouth), followed by Four mesalamine capsules once daily (1.5g/d) for another 12 weeks, PO (by mouth). | 18 |
| Total | 33 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| First 12 Weeks | Adverse Event | 2 | 0 |
| First 12 Weeks | Death | 1 | 1 |
| First 12 Weeks | Withdrawal by Subject | 1 | 1 |
| Second 12 Weeks | Withdrawal by Subject | 0 | 1 |
Baseline characteristics
| Characteristic | Mesalamine Then Placebo | Placebo Then Mesalamine | Total |
|---|---|---|---|
| Age, Continuous | 53 years | 60 years | 55 years |
| Region of Enrollment United States | 15 participants | 18 participants | 33 participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 15 Participants | 18 Participants | 33 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 2 / 31 | 0 / 29 |
| serious Total, serious adverse events | 1 / 31 | 1 / 29 |
Outcome results
Primary
Log(10) Change in % Activated (CD38+HLA-DR+)CD8+ T Cells During the First 12 Weeks of Study
Time frame: Week 0, Week 12
Population: 1 participant assigned to first receive Mesalamine was excluded from analysis due to having withdrawn participation without receiving the allocated intervention
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Mesalamine Then Placebo | Log(10) Change in % Activated (CD38+HLA-DR+)CD8+ T Cells During the First 12 Weeks of Study | 0.03 Log10(percentage of T cells) |
| Placebo Then Mesalamine | Log(10) Change in % Activated (CD38+HLA-DR+)CD8+ T Cells During the First 12 Weeks of Study | -0.01 Log10(percentage of T cells) |
p-value: 0.63t-test, 2 sided
Secondary
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
Time frame: Week 12, Week 24
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Mesalamine Then Placebo | Log(10) Change in % Activated (CD38+HLA-DR+)CD8+ T Cells After Treatment Crossover | 0.003 Log10(percentage of T cells) |
| Placebo Then Mesalamine | Log(10) Change in % Activated (CD38+HLA-DR+)CD8+ T Cells After Treatment Crossover | -0.03 Log10(percentage of T cells) |
p-value: 0.77t-test, 2 sided