LIFE-HIV: Losartan to Reduce Inflammation and Fibrosis Endpoints in HIV Trial
Study Details
Study Description
Brief Summary
The purpose of this study is to evaluate the potential effectiveness of losartan (100mg daily) for reducing inflammation and improving immune recovery.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
Detailed Description
Our general goal is to evaluate the potential effectiveness of losartan (100mg daily) for reducing inflammation and improving immune recovery, given the potential for these treatment effects to reduce risk for long-term non-AIDS-defining complications among older HIV positive participants. Prior to conducting a clinical outcome trial, candidate treatments must be studied among HIV positive patients given the unique pathogenesis driving inflammation and disease risk.
The potential benefits of losartan (100mg daily) will be studied among HIV positive individuals over age 50 years whose CD4 counts remain ≤600 cells/mm3. Participants (n=110, 55 per group) will be randomized to receive losartan or matching placebo daily. After randomization, participants will start losartan (or placebo) at a dose of 50mg once daily, increasing to 100mg once daily at the 2-week study visit pending results of a week 2 toxicity lab evaluation (see 2.4 below for criteria). Following month 1, participants will return for follow-up study visit procedures at months 3, 6, 9, and 12.
Changes from baseline in measures of inflammation, immune activation, immune recovery and fibrosis within lymphatic tissues will be studied. The primary outcome will be the average of IL-6 levels over 12 months, and the main secondary outcome will be change in CD4 count in blood over 12 months.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Active Comparator: Treatment Losartan 100mg daily |
Drug: Losartan 100mg daily
|
| Placebo Comparator: Placebo Matching placebo |
Drug: Matching placebo
|
Outcome Measures
Primary Outcome Measures
- Change in Interleukin 6 (IL-6) Plasma Levels From Baseline to 12 Months [Baseline and 12 months]
Difference between treatment and control IL-6 plasma levels from pre-treatment to on-treatment values
Secondary Outcome Measures
- Change in CD4+ Cell Count From Baseline to 12 Months. [Baseline and 12 months]
Change in cluster of differentiation 4 (CD4+) cell count from baseline to 12 months
Eligibility Criteria
Criteria
Inclusion Criteria:
-
HIV infection (verified by previous positive antibody or detectable HIV RNA level)
-
Age > 50 years
-
Receiving continuous ART for >= 2 years (regimen changes > 6 months prior to enrollment are allowed)
-
HIV RNA level < 200 copies/mL for >= 1 year (1 measure >= 200 allowed if also < 1000 and preceded and followed by values < 200 copies/mL)
-
Blood CD4+ T-cell count < 600 cells/mm cubed
-
Systolic blood pressure > 120 mmHg (mean value if >= 2 measures obtained)
-
Estimated glomerular filtration rate (GFR )> 30 mL/min/1.73 m squared
-
Do not anticipate starting or stopping statin or aspirin therapy during the study
Exclusion Criteria:
-
Pregnancy or breastfeeding
-
A contra-indication to taking an angiotensin receptor blocker (ARB) (e.g., cirrhosis, prior angioedema with angiotensin-converting enzyme inhibitor (ACE-I), or use of drug with potential drug-interaction [e.g., rifaximin])
-
A clinical indication for ARB or ACE-I therapy (e.g., cardiovascular disease (CVD), stroke, or diabetes mellitus (DM))
-
Current treatment with ARB or medication with overlapping mechanism (e.g., ACE-I or aldosterone antagonist)
-
Current treatment with immunomodulatory drugs within the past 6 months
-
Current hepatitis treatments (e.g., interferon, ribavirin) within the past 6 months
-
Serum potassium > 5.0 millimoles per liter (mmol/L) within 3 months of entry
-
Invasive cancer in the prior year or receiving cancer treatment (not including carcinoma-in-situ or basal cell cancer of the skin)
-
Cirrhosis or end-stage liver disease
-
Rheumatologic or chronic inflammatory disease (e.g., systematic lupus erythematous, psoriasis, rheumatoid arthritis, vasculitis, sarcoidosis, Crohn's disease)
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | UCSF | San Francisco | California | United States | 94110 |
| 2 | NIH Clinical Center | Bethesda | Maryland | United States | 20892 |
| 3 | Allina Health | Minneapolis | Minnesota | United States | 55407 |
| 4 | Hennepin County Medical Center | Minneapolis | Minnesota | United States | 55417 |
Sponsors and Collaborators
- Hennepin Healthcare Research Institute
Investigators
- Principal Investigator: Jason Baker, M.D., Hennepin Healthcare Research Institute
Study Documents (Full-Text)
More Information
Publications
None provided.- PCC-007
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | Treatment (Losartan) | Placebo |
|---|---|---|
| Arm/Group Description | Participants receive Losartan 100mg daily | Participants receive a matching placebo daily |
| Period Title: Overall Study | ||
| STARTED | 52 | 56 |
| COMPLETED | 50 | 55 |
| NOT COMPLETED | 2 | 1 |
Baseline Characteristics
| Arm/Group Title | Treatment (Losartan) | Placebo | Total |
|---|---|---|---|
| Arm/Group Description | Participants receive Losartan 100mg daily | Participants receive a matching placebo daily | Total of all reporting groups |
| Overall Participants | 52 | 56 | 108 |
| Age (years) [Mean (Inter-Quartile Range) ] | |||
| Mean (Inter-Quartile Range) [years] |
57
|
57
|
57
|
| Sex: Female, Male (Count of Participants) | |||
| Female |
2
3.8%
|
2
3.6%
|
4
3.7%
|
| Male |
50
96.2%
|
54
96.4%
|
104
96.3%
|
| Race/Ethnicity, Customized (Count of Participants) | |||
| Hispanic |
4
7.7%
|
2
3.6%
|
6
5.6%
|
| Not Hispanic - Black |
15
28.8%
|
22
39.3%
|
37
34.3%
|
| Not Hispanic - White |
31
59.6%
|
29
51.8%
|
60
55.6%
|
| Not Hispanic - Other |
2
3.8%
|
3
5.4%
|
5
4.6%
|
| Region of Enrollment (participants) [Number] | |||
| United States |
52
100%
|
56
100%
|
108
100%
|
| IL-6 (pg/mL) [Median (Inter-Quartile Range) ] | |||
| Median (Inter-Quartile Range) [pg/mL] |
0.91
|
1.04
|
0.97
|
Outcome Measures
| Title | Change in Interleukin 6 (IL-6) Plasma Levels From Baseline to 12 Months |
|---|---|
| Description | Difference between treatment and control IL-6 plasma levels from pre-treatment to on-treatment values |
| Time Frame | Baseline and 12 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Treatment | Placebo |
|---|---|---|
| Arm/Group Description | Losartan 100mg daily Losartan 100mg daily | Matching placebo Matching placebo |
| Measure Participants | 52 | 56 |
| Mean (Standard Deviation) [pg/mL] |
0.14
(1.22)
|
0.29
(1.25)
|
| Title | Change in CD4+ Cell Count From Baseline to 12 Months. |
|---|---|
| Description | Change in cluster of differentiation 4 (CD4+) cell count from baseline to 12 months |
| Time Frame | Baseline and 12 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Treatment (Losartan) | Placebo |
|---|---|---|
| Arm/Group Description | Participants receive Losartan 100mg daily | Participants receive a matching placebo daily |
| Measure Participants | 52 | 56 |
| Mean (Standard Error) [Cells/mm^3] |
15.1
(7.6)
|
6.8
(7.3)
|
Adverse Events
| Time Frame | 12 months | |||
|---|---|---|---|---|
| Adverse Event Reporting Description | ||||
| Arm/Group Title | Treatment (Losartan) | Placebo | ||
| Arm/Group Description | Losartan 100mg provided daily | Matching placebo provided daily | ||
All Cause Mortality |
||||
| Treatment (Losartan) | Placebo | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/52 (0%) | 0/56 (0%) | ||
Serious Adverse Events |
||||
| Treatment (Losartan) | Placebo | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 6/52 (11.5%) | 4/56 (7.1%) | ||
| Gastrointestinal disorders | ||||
| Gastrointestinal Hemorrhage | 0/52 (0%) | 0 | 1/56 (1.8%) | 1 |
| Intestinal Obstruction | 1/52 (1.9%) | 1 | 0/56 (0%) | 0 |
| Infections and infestations | ||||
| Sepsis | 1/52 (1.9%) | 1 | 0/56 (0%) | 0 |
| Pneumonia | 0/52 (0%) | 0 | 1/56 (1.8%) | 1 |
| Respiratory, thoracic and mediastinal disorders | ||||
| Chronic Obstructive Pulmonary Disease | 1/52 (1.9%) | 1 | 0/56 (0%) | 0 |
| Skin and subcutaneous tissue disorders | ||||
| Cellulitis | 1/52 (1.9%) | 1 | 0/56 (0%) | 0 |
| Wound Dehiscence | 1/52 (1.9%) | 1 | 0/56 (0%) | 0 |
| Vascular disorders | ||||
| Mesenteric Vein Thrombosis | 0/52 (0%) | 0 | 1/56 (1.8%) | 1 |
| Ischaemic Stroke | 0/52 (0%) | 0 | 1/56 (1.8%) | 1 |
| Hypoglossal Nerve Disorder | 1/52 (1.9%) | 1 | 0/56 (0%) | 0 |
Other (Not Including Serious) Adverse Events |
||||
| Treatment (Losartan) | Placebo | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 22/52 (42.3%) | 13/56 (23.2%) | ||
| Cardiac disorders | ||||
| Chest Pain | 0/52 (0%) | 0 | 1/56 (1.8%) | 1 |
| Ear and labyrinth disorders | ||||
| Deafness | 1/52 (1.9%) | 1 | 0/56 (0%) | 0 |
| Endocrine disorders | ||||
| Diabetes Mellitus Type 2 | 1/52 (1.9%) | 1 | 1/56 (1.8%) | 1 |
| Gastrointestinal disorders | ||||
| Abdominal Pain | 0/52 (0%) | 0 | 1/56 (1.8%) | 1 |
| Alanine Aminotransferase Increased | 1/52 (1.9%) | 1 | 0/56 (0%) | 0 |
| Aspartate Aminotransferase Increased | 2/52 (3.8%) | 2 | 0/56 (0%) | 0 |
| General disorders | ||||
| Fall | 1/52 (1.9%) | 1 | 0/56 (0%) | 0 |
| Fatigue | 3/52 (5.8%) | 3 | 2/56 (3.6%) | 2 |
| Insomnia | 0/52 (0%) | 0 | 1/56 (1.8%) | 1 |
| Malaise | 3/52 (5.8%) | 3 | 0/56 (0%) | 0 |
| Immune system disorders | ||||
| Leukopenia | 1/52 (1.9%) | 1 | 0/56 (0%) | 0 |
| Musculoskeletal and connective tissue disorders | ||||
| Ligament Sprain | 0/52 (0%) | 0 | 1/56 (1.8%) | 1 |
| Musculoskeletal Pain | 1/52 (1.9%) | 1 | 0/56 (0%) | 0 |
| Myalgia | 1/52 (1.9%) | 1 | 0/56 (0%) | 0 |
| Nervous system disorders | ||||
| Dizziness | 3/52 (5.8%) | 3 | 1/56 (1.8%) | 1 |
| Dysgeusia | 0/52 (0%) | 0 | 1/56 (1.8%) | 1 |
| Somnambulism | 0/52 (0%) | 0 | 1/56 (1.8%) | 1 |
| Vertigo | 1/52 (1.9%) | 1 | 1/56 (1.8%) | 1 |
| Respiratory, thoracic and mediastinal disorders | ||||
| Pneumonia | 1/52 (1.9%) | 1 | 0/56 (0%) | 0 |
| Dyspnoea | 1/52 (1.9%) | 1 | 1/56 (1.8%) | 1 |
| Skin and subcutaneous tissue disorders | ||||
| Skin Abrasion | 0/52 (0%) | 0 | 1/56 (1.8%) | 1 |
| Vascular disorders | ||||
| Hypotension | 1/52 (1.9%) | 1 | 0/56 (0%) | 0 |
Limitations/Caveats
More Information
Certain Agreements
Principal Investigators are NOT 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.
Results Point of Contact
| Name/Title | Jason Baker |
|---|---|
| Organization | Hennepin Healthcare Research Institute |
| Phone | 612-873-2705 |
| baker@umn.edu |
- PCC-007