Phase 2
Completed N=52
Reversing Tissue Fibrosis to Improve Immune Reconstitution in HIV
Source: ClinicalTrials.gov NCT01852942 ↗Enrolled (actual)
52
Serious AEs
15.4%
Results posted
Dec 2020
Primary outcomePrimary: Collagen Deposition in LT — 34.866; 31.02; 30.8925; 29.4492 percent area
Summary
This study was designed to test the hypothesis that treatment of HIV infected subjects with losartan, an agent with specific anti-inflammatory and anti-fibrotic actions, will:
1. reverse existing lymphoid tissue fibrosis,
2. restore lymphoid tissue architecture,
3. increase the number and improve the function of peripheral and lymphatic CD4 T cells,
4. decrease levels of systemic immune activation (IA),
5. decrease size of the HIV reservoir, and
6. be safe and well tolerated.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Collagen Deposition in LT |
34.866; 31.02; 30.8925; 29.4492 | — |
| PRIMARY Integrity of the Fibroblastic Reticular Cell Network (FRCn) |
— | — |
| SECONDARY Frequency of CD4+ T Cells |
— | — |
| SECONDARY Frequency TUNEL+CD3+CD8+ T Cells |
— | — |
| SECONDARY Frequency of Cells Expressing TGF-beta and Lymphotoxin-beta |
— | — |
| SECONDARY Serum Concentration of IL-7 |
— | — |
| SECONDARY Serum Concentration of TGF-beta |
— | — |
| SECONDARY Immune Response to HPV Vaccination |
— | — |
| SECONDARY Frequency of Activated T-cell Populations - Immunofluorescent Staining |
— | — |
| SECONDARY Percent of Activated T Cells in PBMCs - Flow Cytometry |
— | — |
| SECONDARY Percent of Activated Macrophages in PBMCs - Flow Cytometry |
— | — |
| SECONDARY Percent of Activated Dendritic Cells in PBMCs - Flow Cytometry |
— | — |
| SECONDARY Percent of Activated T Cells in LT - Flow Cytometry |
— | — |
| SECONDARY Percent of Activated Macrophages in LT - Flow Cytometry |
— | — |
| SECONDARY Percent of Activated Dendritic Cells in LT - Flow Cytometry |
— | — |
| SECONDARY Intracellular Concentration of IL-17 in PBMCs |
— | — |
| SECONDARY Intracellular Concentration of IFNg in PBMCs |
— | — |
| SECONDARY Intracellular Concentration of IL-2 in PBMCs |
— | — |
| SECONDARY Intracellular Concentration of TNF in PBMCs |
— | — |
| SECONDARY Intracellular Concentration of IL-10 in PBMCs |
— | — |
| SECONDARY Intracellular Concentration of GM-CSF in PBMCs |
— | — |
| SECONDARY Intracellular Concentration of IL-17 in LT |
— | — |
| SECONDARY Intracellular Concentration of IFNg in LT |
— | — |
| SECONDARY Intracellular Concentration of IL-2 in LT |
— | — |
| SECONDARY Intracellular Concentration of TNF in LT |
— | — |
| SECONDARY Intracellular Concentration of IL-10 in LT |
— | — |
| SECONDARY Intracellular Concentration of GM-CSF in LT |
— | — |
| SECONDARY Plasma Concentration of LPS |
— | — |
| SECONDARY Plasma Concentration of sCD14 |
— | — |
| SECONDARY Plasma Concentration of I-FABP |
— | — |
| SECONDARY Plasma Concentration of IL-1b |
— | — |
| SECONDARY Plasma Concentration of IL-1RA |
— | — |
| SECONDARY Plasma Concentration of IL-6 |
— | — |
| SECONDARY Plasma Concentration of TNF |
— | — |
| SECONDARY Plasma Concentration of Amyloid A |
— | — |
| SECONDARY Plasma Concentration of CRP |
— | — |
| SECONDARY Plasma Concentration of D-dimer |
— | — |
| SECONDARY Frequency of HIV RNA+ and DNA+ Cells in LN - Radiolabeled ISH |
— | — |
| SECONDARY Frequency of HIV RNA+ and DNA+ Cells in LN - RNAscopeTM in Situ Technology |
— | — |
| SECONDARY Frequency of HIV RNA+ and DNA+ Cells in GALT - Radiolabeled in Situ Hybridization (ISH) |
— | — |
| SECONDARY Frequency of HIV RNA+ and DNA+ Cells in GALT - RNAscopeTM in Situ Technology |
— | — |
| SECONDARY Concentration of Losartan and Antiretrovirals (ARVs) |
— | — |
| SECONDARY Intracellular Concentration of Losartan and Antiretrovirals (ARVs) |
— | — |
Eligibility Criteria
HIV infected participants:
- Inclusion Criteria:
Participants must meet all of the following inclusion criteria to participate in this study:
- HIV-1 infected.
-≥ 18 years of age.
- Baseline peripheral CD4+ T cell count 200-600 cells/mm3 for at least two measures over the 6 months prior to study enrollment.
-≥ 12 months of stable ART, defined as use of a given drug regimen without disruption lasting ≥ 1 week in the period leading up to study enrollment.
- HIV viral load (VL) 3 times the upper limit of normal within 4 weeks of study enrollment.
- Potassium > 5.0 within 4 weeks of study enrollment.
- Pregnancy.
- In women of childbearing age, unwillingness to use birth control for the duration of the study.
- Breast feeding.
- Prior vaccination with an HPV vaccine, including Cervarix (GlaxoSmithKline) or Gardasil (Merck).
- History of hypersensitivity or severe allergic reactions to yeast.
HIV-uninfected:
- Inclusion Criteria
Participants must meet all of the following inclusion criteria to participate in this study:
- HIV uninfected.
-≥ 18 years of age.
- No contraindication to proposed study procedures.
- Exclusion Criteria: Participants meeting any of the following exclusion criteria at baseline will be excluded from study participation:
- Use of any immunomodulator within the 12 months prior to study enrollment (as defined above).
- Current use of an ARB or ACEi.
- Prior diagnosis of a chronic inflammatory disease with serologic or clinical evidence (as defined above).
- Prior diagnosis of a connective tissue disease with genetic, serologic or clinical evidence as diagnosed by a primary care physician or specialist (Marfan's syndrome, Ehlers-Danlos syndrome).
- Pregnancy.
Data sourced from ClinicalTrials.gov (NCT01852942). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.