A Clinical Trial to Assess the Safety of Oral SRT2104 and Its Effects on Vascular Dysfunction in Otherwise Healthy Cigarette Smokers and Subjects With Type 2 Diabetes Mellitus

Summary

The primary purpose of this study is to evaluate the safety and tolerability of SRT2104 (2.0 g administered once daily for 28 days) and to examine the effects of SRT2104 (2.0 g administered once daily for 28 days) on reversing vasomotor and fibrinolytic dysfunction in both type 2 diabetes mellitus patients and otherwise healthy cigarette smokers in a fed state. This study will investigate the effects of SRT2104 on the reduction of platelet activation markers (platelet-monocyte aggregates), and to evaluate the effects of SRT2104 on platelet and monocyte surface markers (P-selectin, CD11b), inflammatory markers (high sensitivity CRP, IL-6, SAA, TNF-α and sCD40L), and markers of oxidative stress (urinary and plasma F2-isoprostanes and nitrotyrosine). Further goals of this study is to characterize the pharmacokinetic profile of SRT2104 after a single dose and multiple administrations in both type 2 diabetes mellitus patients and otherwise healthy cigarette smokers in a fed state, and to explore the effects of SRT2104 on potential biomarkers of activity for glucose control (HbA1c, glycated albumin and fructosamine) and/or Sirt1 activation.

Timeline

Start

2010-05-28

Primary completion

2011-10-12

Completion

2011-10-12

Publications

• Noh RM, Venkatasubramanian S, Daga S, Langrish J, Mills NL, Lang NN, Hoffmann E, Waterhouse B, Newby DE, Frier BM. Cardiometabolic effects of a novel SIRT1 activator, SRT2104, in people with type 2 diabetes mellitus. Open Heart. 2017 Sep 2;4(2):e000647. doi: 10.1136/openhrt-2017-000647. eCollection 2017.
• Venkatasubramanian S, Noh RM, Daga S, Langrish JP, Mills NL, Waterhouse BR, Hoffmann E, Jacobson EW, Lang NN, Frier BM, Newby DE. Effects of the small molecule SIRT1 activator, SRT2104 on arterial stiffness in otherwise healthy cigarette smokers and subjects with type 2 diabetes mellitus. Open Heart. 2016 May 17;3(1):e000402. doi: 10.1136/openhrt-2016-000402. eCollection 2016.
• Venkatasubramanian S, Noh RM, Daga S, Langrish JP, Joshi NV, Mills NL, Hoffmann E, Jacobson EW, Vlasuk GP, Waterhouse BR, Lang NN, Newby DE. Cardiovascular effects of a novel SIRT1 activator, SRT2104, in otherwise healthy cigarette smokers. J Am Heart Assoc. 2013 Jun 14;2(3):e000042. doi: 10.1161/JAHA.113.000042.

Drugs

Indications