Effects of the small molecule SIRT1 activator, SRT2104 on arterial stiffness in otherwise healthy cigarette smokers and subjects with type 2 diabetes mellitus.

Objective: Arterial stiffness increases with age, and is associated with adverse cardiovascular outcome including increased mortality. The effect of the oral small molecule SIRT1 activator, SRT2104, on arterial stiffness was examined in otherwise healthy cigarette smokers and participants with type 2 diabetes mellitus.

Methods: 24 otherwise healthy cigarette smokers and 15 people with stable type 2 diabetes were randomised in a double-blind placebo-controlled crossover trial and received 28 days of oral SRT2104 (2.

A Randomized, Placebo-Controlled Study of SRT2104, a SIRT1 Activator, in Patients with Moderate to Severe Psoriasis.

Unlabelled: Activation of Sirtuin (silent mating type information regulation 2 homolog) 1, or SIRT1, is an unexplored therapeutic approach for treatment of inflammatory diseases. We randomized 40 patients with moderate-to-severe psoriasis (4:1) to three escalating doses of SRT2104, a selective activator of SIRT1, or placebo. Across all SRT2104 groups, 35% of patients (p<0.

The Selective Sirtuin 1 Activator SRT2104 Reduces Endotoxin-Induced Cytokine Release and Coagulation Activation in Humans.

Objectives: Sirtuin 1 influences gene expression and other cellular functions through deacetylation of histone and nonhistone proteins. We here sought to determine the effects of a small molecule sirtuin 1 activator, SRT2104, on inflammation and coagulation induced by lipopolysaccharide in humans.

Design: A randomized, double-blind, placebo-controlled study.

A phase II, randomized, placebo-controlled, double-blind, multi-dose study of SRT2104, a SIRT1 activator, in subjects with type 2 diabetes.

Aim: SRT2104 is a selective activator of SIRT1. In animal models, SRT2104 improves glucose homeostasis and increases insulin sensitivity. We evaluated the tolerability and pharmacokinetics of SRT2104, and its effects on glycaemic control, in adults with type 2 diabetes mellitus.

Cardiovascular effects of a novel SIRT1 activator, SRT2104, in otherwise healthy cigarette smokers.

Background: We examined the effect of the oral SIRT1 activator SRT2104 on cardiovascular function in otherwise healthy cigarette smokers.

Methods And Results: Twenty-four otherwise healthy cigarette smokers participated in a randomized double-blind, placebo-controlled crossover trial and received 28 days of oral SRT2104 (2.0 g/day) or matched placebo.

Clinical, ethical and financial implications of incidental imaging findings: experience from a phase I trial in healthy elderly volunteers.

Background: The detection of incidental findings (IF) in magnetic resonance imaging (MRI) studies is common and increases as a function of age. Responsible handling of IF is required, with implications for the conduct of research and the provision of good clinical care.

Aim: To investigate the prevalence and clinical significance of IF in a prospective cohort of healthy elderly volunteers who underwent MRI of the torso as a baseline investigation for a phase I trial.

Brief report: a phase IIa, randomized, double-blind, placebo-controlled trial of apilimod mesylate, an interleukin-12/interleukin-23 inhibitor, in patients with rheumatoid arthritis.

Objective: To investigate the safety, tolerability, pharmacokinetics, and efficacy of apilimod mesylate, an oral interleukin-12 (IL-12)/IL-23 inhibitor, in patients with rheumatoid arthritis (RA).

Methods: We performed a phase IIa, randomized, double-blind, placebo-controlled proof-of-concept study of apilimod, in combination with methotrexate, in 29 patients with active RA (3:1 ratio of apilimod-treated to placebo-treated patients) in 3 stages. Patients received apilimod 100 mg/day or placebo for 4 weeks (stage 1) or 8 weeks (stage 2).

Randomized, double-blind, placebo-controlled trial of the oral interleukin-12/23 inhibitor apilimod mesylate for treatment of active Crohn's disease.

Background: Interleukin-12 (IL-12) and interleukin-23 (IL-23) are inflammatory cytokines linked to the Th-1 and Th-17 phenotypes associated with Crohn's disease (CD). We investigated the activity and safety of apilimod mesylate (formerly STA-5326), an oral IL-12 and IL-23 inhibitor, in patients with active CD.

Methods: We performed a multicenter, Phase 2, randomized, double-blinded, placebo-controlled study to evaluate the efficacy of apilimod mesylate in treating 220 adult patients with moderate-to-severe CD (Crohn's Disease Activity Index [CDAI] score 220-450).

Modulation of CCR2 in rheumatoid arthritis: a double-blind, randomized, placebo-controlled clinical trial.

Objective: CCR2 is a chemokine receptor expressed by monocytes, macrophages, and a subset of T cells. Its ligand, CCL2 (monocyte chemotactic protein 1), is abundantly present in the synovium of patients with rheumatoid arthritis (RA). Blocking CCR2 prevents CCL2-mediated chemotaxis in vitro and modulates arthritis in animal models of RA.