Dataset Information

Urine Eicosanoids in the Metabolic Abnormalities, Telmisartan, and HIV Infection (MATH) Trial.

ABSTRACT:

Objectives

Arachidonic acid metabolites (eicosanoids) reflect oxidative stress and vascular health and have been associated with anthropometric measures and sex differences in cross-sectional analyses of HIV-infected (HIV+) persons. Telmisartan is an angiotensin receptor blocker and PPAR-? agonist with potential anti-inflammatory and metabolic benefits. We assessed telmisartan's effects on urine eicosanoids among HIV+ adults with central adiposity on suppressive antiretroviral therapy enrolled in a prospective clinical trial.

Methods

Thirty-five HIV+ adults (15 women; 20 men) completed 24 weeks of open-label oral telmisartan 40mg daily. Lumbar computed tomography quantified visceral (VAT) and subcutaneous (SAT) abdominal adipose tissue. Urine F2-isoprostane (F2-IsoP), prostaglandin E2 (PGE-M), prostacyclin (PGI-M), and thromboxane B2 (TxB-M) were quantified at baseline and 24 weeks using gas/liquid chromatography-mass spectroscopy. Mann-Whitney-U tests compared sub-group differences; Spearman's rho assessed correlations between clinical factors and eicosanoid levels.

Results

Median PGE-M increased on telmisartan (p<0.01), with greater changes in men (+4.1 [p = 0.03] vs. +1.0 ng/mg cr in women; between-group p = 0.25) and participants losing >5% VAT (+3.7 ng/mg cr, p<0.01) and gaining >5% SAT (+1.7 ng/mg cr, p = 0.04). Median baseline F2-IsoP and TxB-M were slightly higher in women (both between-group p = 0.08) and did not change on telmisartan.

Conclusions

Urine PGE-M increased with 24 weeks of telmisartan in virally suppressed, HIV+ adults with central adiposity. Associations with favorable fat redistribution suggest increased PGE-M may reflect a beneficial response.

SUBMITTER: Le CN

PROVIDER: S-EPMC5261803 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Urine Eicosanoids in the Metabolic Abnormalities, Telmisartan, and HIV Infection (MATH) Trial.

Le Catherine N CN Hulgan Todd T Tseng Chi-Hong CH Milne Ginger L GL Lake Jordan E JE

PloS one 20170124 1

<h4>Objectives</h4>Arachidonic acid metabolites (eicosanoids) reflect oxidative stress and vascular health and have been associated with anthropometric measures and sex differences in cross-sectional analyses of HIV-infected (HIV+) persons. Telmisartan is an angiotensin receptor blocker and PPAR-γ agonist with potential anti-inflammatory and metabolic benefits. We assessed telmisartan's effects on urine eicosanoids among HIV+ adults with central adiposity on suppressive antiretroviral therapy en ...[more]

PMID: 28118376

Similar Datasets

Project description:BACKGROUND:Higher levels of small low-density lipoprotein (LDL) and lower levels of high-density lipoprotein (HDL) subclasses have been associated with increased risk of cardiovascular disease. The extent to which HIV infection and HIV/hepatitis C virus (HCV) coinfection are associated with abnormalities of lipoprotein subclasses is unknown. METHODS:Lipoprotein subclasses were measured by nuclear magnetic resonance (NMR) spectroscopy in plasma samples from 569 HIV-infected and 5948 control participants in the Fat Redistribution and Metabolic Change in HIV Infection (FRAM), Coronary Artery Risk Development in Young Adults (CARDIA), and Multi-Ethnic Study of Atherosclerosis (MESA) studies. Multivariable regression was used to estimate the association of HIV and HIV/HCV coinfection with lipoprotein measures with adjustment for demographics, lifestyle factors, and waist-to-hip ratio. RESULTS:Relative to controls, small LDL levels were higher in HIV-monoinfected persons (+381?nmol/l, P?<0.0001), with no increase seen in HIV/HCV coinfection (-16.6?nmol/l). Levels of large LDL levels were lower (-196?nmol/l, P?<0.0001) and small HDL were higher (+8.2??mol/l, P?<?0.0001) in HIV monoinfection with intermediate values seen in HIV/HCV coinfection. Large HDL levels were higher in HIV/HCV-coinfected persons relative to controls (+1.70??mol/l, P?<0.0001), whereas little difference was seen in HIV-monoinfected persons (+0.33, P?=?0.075). Within HIV-infected participants, HCV was associated independently with lower levels of small LDL (-329?nmol/l, P?<0.0001) and small HDL (-4.6??mol/l, P?<0.0001), even after adjusting for demographic and traditional cardiovascular risk factors. CONCLUSION:HIV-monoinfected participants had worse levels of atherogenic LDL lipoprotein subclasses compared with controls. HIV/HCV coinfection attenuates these changes, perhaps by altering hepatic factors affecting lipoprotein production and/or metabolism. The effect of HIV/HCV coinfection on atherosclerosis and the clinical consequences of low small subclasses remain to be determined.

Project description:Students in many western countries struggle to achieve acceptable standards in numeracy despite its recognition as an important 21st century skill. As commercial math programs remain a staple of classroom instruction, investigations of their effectiveness are essential to inform decision-making regarding how to invest limited resources while maximizing student gains. We conducted a cluster randomized-controlled trial of the effectiveness of JUMP Math, a distinctive math program whose central tenets are empirically supported, for improving elementary math achievement (clinical trial.gov no. NCT02456181). The study involved 554 grade 2 (primary) and 592 grade 5 (junior) students and 193 teachers in 41 schools, in an urban-rural Canadian school board. Schools were randomly assigned to use either JUMP Math or their business-as-usual, problem-based approach to math instruction. We tracked student progress in math achievement on standardized and curriculum-based measures of computation and problem solving, for 2 consecutive school years. Junior students taught with JUMP Math made significantly greater progress in computation than their non-JUMP peers but the groups did not differ significantly in problem solving. Effects took hold relatively quickly, replicating the results from an earlier pilot study. Primary students in the non-JUMP group made significantly greater gains in problem solving and computation in year 1. But those taught with JUMP Math made significantly greater gains in problem solving and the groups did not differ in computation, in year 2. The positive effects of JUMP Math are noteworthy given that the JUMP Math teachers were likely still adjusting to the new program. That these positive findings were obtained in an effectiveness study (i.e. in real-world conditions), suggests that JUMP Math may be a valuable evidence-based addition to the teacher's toolbox. Given the importance of numeracy for 21st century functioning, identifying and implementing effective math instruction programs could have far-reaching, positive implications.

Project description:INTRODUCTION:Telmisartan, an angiotensin receptor blocker, has beneficial effects on insulin resistance and cardiovascular health in non-HIV populations. This trial will evaluate whether telmisartan can reduce insulin resistance in HIV-positive individuals on combination antiretroviral therapy. METHODS AND ANALYSIS:This is a phase II, multicentre, randomised, open-labelled, dose-ranging trial of telmisartan in 336 HIV-positive individuals over a period of 48?weeks. The trial will use an adaptive design to inform the optimal dose of telmisartan. Patients will be randomised initially 1:1:1:1 to receive one of the three doses of telmisartan (20, 40 and 80?mg) or no intervention (control). An interim analysis will be performed when half of the planned maximum of 336 patients have been followed up for at least 24?weeks. The second stage of the study will depend on the results of interim analysis. The primary outcome measure is a reduction in insulin resistance (as measured by Homeostatic Model Assessment-Insulin Resistance (HOMA-IR)) in telmisartan treated arm(s) after 24?weeks of treatment in comparison with the non-intervention arm. The secondary outcome measures include changes in lipid profile; body fat redistribution (as measured by MRI); plasma and urinary levels of various biomarkers of cardiometabolic and renal health at 12, 24 and 48?weeks. Serious adverse events will be compared between different telmisartan treated dose arm(s) and the control arm. ETHICS AND DISSEMINATION:The study, this protocol and related documents have been approved by the National Research Ethics Service Committee North West-Liverpool Central (Ref: 12/NW/0214). On successful completion, study data will be shared with academic collaborators. The findings from TAILoR will be disseminated through peer-reviewed publications, at scientific conferences, the media and through patient and public involvement. TRIAL REGISTRATION NUMBERS:04196/0024/001-0001; EUDRACT:2012-000935-18; ISRCTN:51069819.

Dataset Information

Urine Eicosanoids in the Metabolic Abnormalities, Telmisartan, and HIV Infection (MATH) Trial.

Objectives

Methods

Results

Conclusions

Publications

Urine Eicosanoids in the Metabolic Abnormalities, Telmisartan, and HIV Infection (MATH) Trial.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure