Clinical trials

You can read an accessible summary here of clinical trials for members of the public.

One of the main focuses of CADET is the development of experimental therapeutics . We currently have one therapeutic (Trientine) that has already undergone clinical trials and we hope it will become a valuable therapy for the treatment of the complications of diabetes. Because it has already been shown to be effective in correcting defects in copper homeostasis, we hypothesise that it could be used in other chronic conditions where copper dysfunction might play a role in pathogenesis – the current trial described below is an example of this.

Other experimental therapeutics under development are in the pre-clinical stages and we are investigating their potential in the treatment of diabetes and dementias. Two of our PhD students’ projects are in this area.

Trientine

Trientine dihydrochloride (or Triethylenetetramine (TETA)) is a copper-chelating agent licenced in the UK, Europe and the USA for treating Wilson’s disease, a rare disorder of copper excretion, which leads to excess copper accumulation and associated tissue injury. We have shown in pre-clinical models of diabetes that Trientine reverses the effects of diabetic cardiomyopathy and diabetic nephropathy. In a clinical trial for diabetic left-ventricular hypertrophy, patients treated with Trientine for 12 months had a 10% decrease in left ventricular mass indexed to body surface area compared with placebo-treated patients [1].

Clinical Trial: A novel treatment for Hypertrophic Cardiomyopathy

Hypertrophic cardiomyopathy (HCM) is the most common inherited heart condition and is the leading cause of sudden death in young people. It is characterised by myocardial hypertrophy and can lead to heart failure and abnormal heart rhythms. The mechanism by which the genetic mutations lead to the phenotypic alterations is not fully understood, but there is increasing evidence that abnormal myocardial energy handling/energy depletion (myocardial energetics), impaired mitochondrial function and oxidative stress play key roles. There are currently no treatments that alter the natural history of HCM and the National Institutes of Health has identified a “critical need” for clinical studies of drug therapies that target putative pathways of HCM disease pathogenesis.

An open-label pilot study of Trientine in HCM in which 20 patients will receive Trientine for six months is currently underway in the University Hospital of South Manchester [2]. Patients will undergo assessments of myocardial energetics, myocardial mass, fibrosis, diastolic function (using cardiac magnetic resonance imaging and echocardiography) and exercise capacity at baseline and after six months of therapy. We hypothesise that Trientine will lead to a significant improvement in myocardial energetics (primary outcome). If this is demonstrated, we believe this result will provide convincing evidence for our hypothesis. Secondary objectives will evaluate the change in left-ventricular mass, fibrosis, diastolic function and exercise capacity.

[1] Cooper GJS, Young AA, et al. ‘A copper(II)-selective chelator ameliorates left-ventricular hypertrophy in type 2 diabetic patients: a randomised placebo-controlled study.’ Diabetologia 2009 52:715-722. [http://www.ncbi.nlm.nih.gov/pubmed/?term= 19172243]

[2] Schmitt M Chief Investigator ‘Copper chelation in hypertrophic cardiomyopathy: open-label pilot study of Trientine in patients with hypertrophic cardiomyopathy.’ [http://public.ukcrn.org.uk/search/StudyDetail.aspx?StudyID=17776]