Table 2.
Ongoing clinical trials of statins and anti-microbial translocation drugs in HIV+ patients to examine anti-inflammatory effects and/or cardiovascular benefits
| Drug | Phase | Randomized? | Cardiovascular and/or inflammation outcomes* | Size | Status | Identifier |
|---|---|---|---|---|---|---|
| Statins | ||||||
| Atorvastatin | n/a | Y | Cardiovascular: coronary and aortic plaque inflammation, plaque progression, endothelial function Inflammation: immune function, CRP |
40 | Completed | NCT00965185 |
| Atorvastatin | 4 | N | Cardiovascular: none specified Inflammation: peripheral blood monocytes, T cell markers |
15 | Active, not recruiting | NCT01263938 |
| Lovastatin | 2 | Y | Cardiovascular: none specified Inflammation: T cell activity (CD4, CD8), CD38, HLA-DR, LFA-1 ICAM-1 |
112 | Completed | NCT00721305 |
| Rosuvastatin calcium | 0 | Y | Cardiovascular: cEMT, FMD Inflammation: hsCRP | 30 | Completed | NCT01881971 |
| Atorvastatin | 4 | Y | Cardiovascular: none specified Inflammation: peripheral blood monocytes, T cell, and CSF activation markers |
30 | Recruiting | NCT01600170 |
| Pravastatin sodium vs efavirenz/emtricitabine/tenofovir disoproxil fumarate | 2 | Y | Cardiovascular: brachial artery FMD Inflammation: IL-6, hs-CRP, D-dimer | 0 | Withdrawn | NCT01515813 |
| Atorvastatin | 2 | Y | Cardiovascular: none specified Inflammation: markers of inflammation (not specified further) |
9 | Completed | NCT003 67458 |
| Atorvastatin | 4 | Y | Inflammation: IL-6, antiretroviral resistance test | 60 | Recruiting | NCT02577042 |
| Rosuvastatin | 2 & 3 | N | Cardiovascular: brachial artery FMD, Inflammation: T cell CD38 and CD69, monocyte CD16 and CD69, hsCRP |
7 | Terminated | NCT00986999 |
| Pitavastatin | 4 | Y | Cardiovascular: any major adverse cardiovascular events, evidence of non-calcified coronary atherosclerotic plaque, volume of NCP at study entry and change in NCP over 2 years, progression of NCP, number of high risk plaque features Inflammation: inflammatory markers (not specified further) |
6500 | Recruiting | NCT02344290 |
| Atorvastatin | 2 | Y | Cardiovascular: none specified Inflammation: IL-6, CD4+ T cell activation, D-dimer, CD8+ T cell activation, MCP-1, EP-10, CD40L, sCD14, P-selectin, sCD163 |
98 | Completed | NCT01351025 |
| Atorvastatin | 3 | Y | Cardiovascular: none specified Inflammation: percentage change in immune activation levels after 12 weeks of atorvastatin 80 mg daily |
30 | Completed | NCT01766076 |
| Probiotics | ||||||
| Probiotics | n/a | N | CD4+/CD38-/HLA-DR, CD8+/CD38+/HLA-DR + |CD4 recovery | 30 | Unknown status | NCT02164344 |
| Probiotic | n/a | N | LPS, sCD14, change in inflammation around the gut measured with PET/MR scans of the abdomen, hsCRP, cytokines |
45 | Completed | NCT02764684 |
| Probiotics | n/a | Y | LPS, cytokines and macrophage activation, lymphocyte activation markers, viral load, CD4 T cell count |
0 | Withdrawn | NCT01492803 |
| Multi-strain probiotic | 2 | Y | Measures of microbial translocation, markers of immune activation, immune reconstitution in ART-treated patients |
100 | Unknown status | NCT0143 9841 |
| VSL#3® probiotic | n/a | N | sCD14, sCD163, IL-6, D-dimer, plasma intestinal fatty acid biding protein, CD4+ T cell counts | 23 | Completed | NCT02448238 |
| Probiotic | 2 | Y | LBP, sCD14, interferon gamma, TNF, IL-6, CRP, D-dimer, fibrinogen, CD4 -l- lymphocyte count, CD 8+, and HIV viral load |
44 | Active, not recruiting | NCT01908049 |
| Visbiome | 2 | Y | LPS, sCD14, IL-6, D-dimer, CRP, gut immune cell counts (including CD4 T cell subsets), intestinal permeability (Lac/Mac ratio), gut HIV DNA levels |
40 | Recruiting | NCT02441244 |
| Other Drugs Targeting Microbial Translocation | ||||||
| Lubiprostone | 2 | Y | CD8+ T cell activation, CD8+ T cell activation, CD4+ T cell activation, levels of systemic inflammation, plasma HIV-1 RNA, peripheral CD4+, Actl Antibody |
20 | Active, not recruiting | NCT01839734 |
| Rifaximin | 2 | Y | CD8+ T cell activation, D-dimer, IL-6, LPS, hsCRP, sCD14, Peripheral B7hi CD4+ T cell, %CD3 8+ of CD4+, %CD38+ of CD8+, %Ki67+ ofCD4+, %Ki67+ of CD8+, %HLA-DR+/CD38+ of CD4+, CD38+ of CD8+ mean fluorescence intensity |
73 | Completed | NCT01466595 |
| Teduglutide | 2 | Y | Cardiovascular: arterial target to background ratio of 18-FDG-PET uptake, CD4+ T cell percentage, plaque volume on cardiac computed tomography angiography Inflammation: sCD14, sCD163, intestinal fatty acid binding protein, LPS |
60 | Recruiting | NCT02431325 |
| Fluarix vs pneumovax | Y | CD4+ T cell activity, IL-6, TNF, sCD14, sCD163, CD3, CD4, CD8, CD38, DR, levels of HIV specific immune response |
56 | Recruiting | NCT02707692 | |
| Isotretinoin | 2 | Y | CD8+ T cell activation, markers of gut microbial translocation, markers of systemic inflammation and coagulation, sCD163, CD4+ T cell count, Thl7 and Treg frequency |
76 | Active, not recruiting | NCTO1969058 |
*Only studies that included inflammatory markers as outcomes are included.
Abbreviations: highly-sensitive C-reactive protein, hsCRP; C-reactive protein, CRP; soluble CD14, sCD14; soluble CD163, sCD163; interleukin-6, IL-6; Flow-mediated dilatation, FMD; soluble tumor necrosis factor receptor, sTNFR; tumor necrosis factor, TNF; monocyte chemotactic protein 1,MCP-1; soluble vascular cell adhesion molecule 1, sVCAM-1; interferon gamma-induced protein 10, IP-10; Matrix metallopeptidase, MMP-9; TIMP metallopeptidase inhibitor 1, TIMP-1; Plasminogen activator inhibitor-1, PAI-1; Positron emission tomography, PET; Fluorodeoxygenase, FDG; human leukocyte antigen-antigen D related, HLA-DR