Effect of Glucose on QTc Interval in Type 1 Diabetes
Condition: Diabetes
MeSH terms: Diabetes Mellitus
Study type: Interventional
Phase: Phase 1

Summary: 
      High blood glucose levels (hyperglycaemia) and Moxifloxacin (a commonly used antibiotic) have
      both been shown independently to affect heart activity in healthy volunteers as recorded by
      ECG. i.e. Both cause prolongation of the QTc interval which is a measure of the time between
      the start of the Qwave and the end of the Twave during a heartbeat cycle. In this study, the
      investigators want to find out whether moxifloxacin and hyperglycaemia cause QTc prolongation
      in Type 1 diabetic patients. The investigators also want to assess whether C-peptide (a
      fragment if insulin normally found in the blood but not present in the blood of Type 1
      diabetics) has the opposite effect on heart activity i.e it shortens the QTc interval will
      reverse the effect of QTc prolongation in Type 1 diabetes as this may be useful for
      preventing 'dead in bed' syndrome also known as 'Sudden Cardiac Death' which is more common
      in diabetic patients compared to healthy volunteers.
    

Detailed description: 
      The investigators previous research (Taubel et al., 2013) has shown that in healthy
      individuals glucose by itself can prolong (with C-peptide antagonising the effects) the QT
      interval, which has long been used as a clinical index of the duration of ventricular
      repolarisation. This observation warrants serious attention because it suggests that high
      glucose levels by themselves may be pro-arrhythmogenic. To investigate whether glucose has an
      effect on cardiac repolarisation, it would be advantageous to test this in an environment
      uncomplicated by C-peptide. In order to elucidate the effects of glucose on the QTc in the
      absence of C-peptide, the investigators will use diabetic patients who are no longer able to
      release endogenous C-peptide. This will allow better understanding to whether (1) the well
      established QTc prolongation caused by moxifloxacin is exaggerated by elevated levels of
      blood glucose, which would be important for evaluating the risk in diabetic patients using an
      IKr blocking drug such as moxifloxacin, and (2) to investigate whether C-peptide substitution
      will reverse or attenuate the effect in the presence of moxifloxacin. Using the conditions of
      a formal TQT study, the investigators would also want to confirm the QTc prolonging effects
      described in Gordin et al. (2008) and whether in this setting C-Peptide substitution will
      reverse or attenuate the glucose effect on QTc.

      This will be a phase I, single centre, randomised, placebo-controlled, open-label, crossover
      study designed to evaluate the effect of glucose and C-peptide on cardiac repolarisation
      using a hyperglycaemic clamp and a single 400 mg dose of moxifloxacin as a positive control
      in non-elderly male and female patients with type I diabetes. The results from this study
      will form the basis for decisions for future studies.

      This study will be performed in compliance with the protocol, ICH GCP and applicable
      regulatory requirements including EU GMP requirements for investigational medicinal
      product(s) (IMPs).
    

Intervention name(s): Moxifloxacin; hyper-glycaemic clamp
Intervention type(s): Drug; Other
Intervention description(s): a single oral dose of 400mg Moxifloxacin plus a hyper-glycaemic clamp for 4 hours
a single oral dose of 400mg Moxifloxacin plus C-peptide
a single oral dose of 400mg Moxifloxacin
placebo
Oral doses of placebo and moxifloxacin will be administered by a Research Physician or Pharmacy staff member between 08:00 a.m. and 10:00 a.m.; a hyper-glycaemic clamp only for 2 hours followed by a hyper-glycaemic clamp plus C-peptide for 2 hours
Other intervention name(s): Avelox®; glucose infusion; glucose clamp
Intervention MeSH terms: Moxifloxacin
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: None (Open Label)
Primary purpose: Basic Science
Keywords: Hyperglycaemia; Moxifloxacin; QTc prolongation; C-peptide; Dead in bed syndrome