Effects on Arterial structure & function using ACZ in T2DM & IGT pts

• Research type

  Research Study

• Full title

  A multi center, randomized, double blind, placebo-controlled, study of the safety, tolerability, and the effects on arterial structure and function of ACZ885 in patients with clinically evident atherosclerosis and either type 2 diabetes mellitus(T2DM) or impaired glucose tolerance(IGT)

• IRAS ID

  36244

• Contact name

  Robin Choudhury

• Sponsor organisation

  Novartis Pharma Services AG

• Eudract number

  2009-014618-80

• ISRCTN Number

  n/a

• Research summary

  The objective of the study is to assess the effects of the drug canakinumab (ACZ885) on the structure and function of arteries in people who have either type 2 diabetes (T2DM) or impaired glucose tolerance (IGT), alongside evidence of existing atherosclerosis (for example a previous heart attack).Atherosclerosis is a condition in which an artery wall thickens and becomes inflamed as a result of a build up of fatty materials such as cholesterol. It is commonly referred to as hardening or furring of the arteries. Diabetes is a condition caused when the body's unable to produce or utilise insulin to process sugars properly and so the level of glucose in the blood is too high. Impaired glucose tolerance (IGT) is a transition phase between normal glucose handling and diabetes and is sometimes referred to as prediabetes. Diabetes is a strong driver in the processes that promote atherosclerosis and inflammation has emerged as an important contributor to both diabetes and atherosclerosis.Preclinical data suggest that a biochemical called Interleukin-1?beta (IL-1ǟ÷) is an important driver of inflammation both in (1) atherosclerosis and (2) the pancreas, where it can stop the beta cells from secreting insulin normally. Prior studies have shown that blocking the action of IL-1ǟ÷ can improve arterial function in patients with rheumatoid arthritis and may improve blood sugars in patients with diabetes.Canakinumab (ACZ885) is a fully human monoclonal antibody which is being developed for the treatment of IL-1ǟ÷ driven inflammatory diseases. It is designed to bind to human IL-1ǟ÷ and therefore prevent its action. We hypothesize that Canakinumab will (1) reduce arterial inflammation and that this will be detectable using multimodal magnetic resonance imaging and (2) reduce the destruction of the pancreatic ǟ÷ cells and that this can be detected through blood measurements of glucose and insulin handling.A total of approximately 140 subjects with T2DM or IGT will be recruited into the study, (with approximately 70 of these patients coming from the UK) and will be participating in the study for up to 16 months (this covers from the initial screening to the last visit). Patients will be randomised in a 1: 1 ratio to active treatment or placebo, and will be stratified by glycaemic status: T2DM or IGT, with a target of 35 complete patients for each glycaemic status category.

• REC name

  South Central - Oxford B Research Ethics Committee

• REC reference

  09/H0605/127

• Date of REC Opinion

  20 Jan 2010

• REC opinion

  Further Information Favourable Opinion