NCT01984827

Effect of Glucose on QTc Interval in Type 1 Diabetes

A Single Centre, Placebo Controlled, Phase I Study to Evaluate the Effect of Glucose and Moxifloxacin on Cardiac Repolarisation in Male and Female Patients With Type I Diabetes.

• Status: Completed
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 24 (actual)
• Sponsor: Richmond Research Institute · Industry
• Sex: All
• Age: 20 Years – 64 Years
• Healthy volunteers: Not accepted

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).

Conditions

• Diabetes

Interventions

Type	Name	Description
DRUG	Moxifloxacin	1. a single oral dose of 400mg Moxifloxacin plus a hyper-glycaemic clamp for 4 hours 2. a single oral dose of 400mg Moxifloxacin plus C-peptide 3. a single oral dose of 400mg Moxifloxacin 4. 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.
OTHER	hyper-glycaemic clamp	a hyper-glycaemic clamp only for 2 hours followed by a hyper-glycaemic clamp plus C-peptide for 2 hours

Timeline

• Start date: 2019-02-10
• Primary completion: 2020-12-31
• Completion: 2020-12-31
• First posted: 2013-11-15
• Last updated: 2021-05-05

Locations

1 site across 1 country: United Kingdom