Mesalamine to Reduce T Cell Activation in HIV Infection

• Sponsor: University of California, San Francisco (Other)
• Overall Status: Completed
• CT.gov ID: NCT01090102
• Collaborator: California HIV/AIDS Research Program (Other), Bausch Health Americas, Inc. (Industry)
• Enrollment: 33
• Location: 1
• Arms: 2
• Duration (Months): 30
• Patients Per Site Per Month: 1.1

Study Details

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.

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

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 Design

• Study Type: Interventional
• Actual Enrollment: 33 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: Mesalamine to Reduce T Cell Activation in HIV Infection
• Study Start Date: Jun 1, 2010
• Actual Primary Completion Date: Dec 1, 2012
• Actual Study Completion Date: Dec 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
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).

Outcome Measures

Primary Outcome Measures

1. 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

1. 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

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	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
• Bausch Health Americas, Inc.

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: University of California, San Francisco
• ClinicalTrials.gov Identifier: NCT01090102
• Other Study ID Numbers: 164320
• First Posted: Mar 19, 2010
• Last Update Posted: Aug 13, 2014
• Last Verified: Aug 1, 2014

• Additional relevant MeSH terms: Infections; Communicable Diseases; HIV Infections; Acquired Immunodeficiency Syndrome; Sexually Transmitted Diseases; Lentivirus Infections; Immunologic Deficiency Syndromes; Immune System Diseases; Aminosalicylic Acid; Mesalamine

Study Results

Participant Flow

Arm/Group Title	Mesalamine Then Placebo	Placebo Then Mesalamine
Arm/Group Description	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).	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).
Period Title: First 12 Weeks
STARTED	15	18
COMPLETED	11	16
NOT COMPLETED	4	2
Period Title: First 12 Weeks
STARTED	11	16
COMPLETED	11	15
NOT COMPLETED	0	1

Baseline Characteristics

Arm/Group Title	Mesalamine Then Placebo	Placebo Then Mesalamine	Total
Arm/Group Description	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).	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).	Total of all reporting groups
Overall Participants	15	18	33
Age (years) [Median (Inter-Quartile Range) ]
Median (Inter-Quartile Range) [years]	53	60	55
Sex: Female, Male (Count of Participants)
Female	0 0%	0 0%	0 0%
Male	15 100%	18 100%	33 100%
Region of Enrollment (participants) [Number]
United States	15 100%	18 100%	33 100%

Outcome Measures

1. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

1 participant assigned to first receive Mesalamine was excluded from analysis due to having withdrawn participation without receiving the allocated intervention

Arm/Group Title	Mesalamine Then Placebo	Placebo Then Mesalamine
Arm/Group Description	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).	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).
Measure Participants	14	18
Mean (95% Confidence Interval) [Log10(percentage of T cells)]	0.03	-0.01

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Mesalamine Then Placebo, Placebo Then Mesalamine
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.63
	Comments	Significant at p<0.05
	Method	t-test, 2 sided
	Comments

2. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Mesalamine Then Placebo	Placebo Then Mesalamine
Arm/Group Description	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).	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).
Measure Participants	11	16
Mean (95% Confidence Interval) [Log10(percentage of T cells)]	0.003	-0.03

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Mesalamine Then Placebo, Placebo Then Mesalamine
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.77
	Comments	significant at p<0.05
	Method	t-test, 2 sided
	Comments

Adverse Events

Time Frame	24 weeks
Arm/Group Title	Mesalamine		Placebo
Arm/Group Description	Mesalamine (5-aminosalicylic acid, Apriso): Four mesalamine capsules once daily (1.5 gram/day) PO(by mouth).		Placebo: Four placebo capsules once daily (1.5g/d) PO (by mouth).
All Cause Mortality
	Mesalamine		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Mesalamine		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/31 (3.2%)		1/29 (3.4%)
General disorders
Death	1/31 (3.2%)		1/29 (3.4%)
Other (Not Including Serious) Adverse Events
	Mesalamine		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/31 (6.5%)		0/29 (0%)
General disorders
Drug relapse	1/31 (3.2%)		0/29 (0%)
Hepatobiliary disorders
Liver Cirrhosis	1/31 (3.2%)		0/29 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.