Use of Diazoxide in Acute Hypoglycaemia
Condition: Type 1 Diabetes
MeSH terms: Diabetes Mellitus, Type 1; Hypoglycemia
Study type: Interventional
Phase: Phase 4

Summary: 
      The investigators know that intensive insulin therapy and tight glucose control is associated
      with reduction of diabetic complications. However, many patients on insulin don't achieve
      this because of the risk and the fear of hypoglycaemia (too low blood glucose).

      There has been a lot of work done recently looking at the mechanisms by which the brain
      detects hypoglycaemia. A key player is a potassium channel in the brain (KATP channel).
      Studies have shown that when these channels are opened, there is a release of hormones such
      as adrenaline that can help in raising blood sugars to counteract and increase awareness of
      hypoglycaemia. The investigators study aims to look at an old drug called diazoxide, which is
      able to open KATP channels.

      The investigators aim to see if diazoxide will amplify the release of hormones such as
      adrenaline when the blood sugar is low. If this is the case, this will aid quicker recovery
      following hypoglycaemia.

      The investigators aim to do this by performing a well established experimental protocol that
      has been performed safely over the last 20 years called a clamp study. The clamp study will
      involve slowly bringing the blood sugars down using insulin and intravenous glucose in a
      controlled fashion. The main outcome will be the hormonal responses (adrenaline response) at
      a blood sugar level of 2.5mmol/L. Symptoms of hypoglycaemia will be monitored, as well as
      working memory tests using standardised questionnaires.

      The design of the investigators study will be a randomised trial comparing the effects of
      diazoxide with placebo in which all patients will receive both diazoxide and placebo in
      random order (crossover design).
    

Detailed description: 
      This will be conducted in a double blinded (neither subject nor the researcher will know the
      order of the IMP(drug/placebo). All subjects will receive both the active drug and placebo in
      a random fashion (crossover design).

      Once identified, patients will be given a participant information sheet. They will be
      contacted at a later date (minimum 24 hours) to determine if they are willing to participate
      in the trial.

      Subjects will then be consented, and attend a screening visit, where it will be ascertained
      whether they fit the inclusion/exclusion criteria. Further details of the study will also be
      given to them at this visit. They will then attend a few days before the first study, and
      will be shown how to use the continuous glucose monitor which will measure their glucose
      overnight, prior to the start of the study. The reason for this, is that if they have very
      low blood sugars the night before the study, this can influence the results of the study, and
      they will be given an alternative day to attend. Provided they have been free of any
      hypoglycaemic episodes, the night before, they can then proceed with the study.

      On the day of the study,we will place two intravenous cannulae. The cannulae in the hand vein
      will be placed in a warm chamber, in order to make it more more reflective of sampling at the
      blood brain barrier.

      The subject will either have the investigational medicinal product (diazoxide) or placebo.
      Blood pressure and heart rate will be monitored throughout the clamp study. After 2 hours,
      with the use of insulin and dextrose, the subject's blood sugar will be brought to near
      normal and kept there for 40 minutes. After this, the blood sugar will be dropped in stages,
      until a blood sugar of 2.5mmol/L is reached. The blood sugar will be monitored very closely,
      with 5 minute sampling taken through one of the cannulue in situ, to avoid repeated stabbing.
      Also at regular intervals, blood samples will be taken for measurement of hormones, including
      adrenaline. At each stage, subjects will be asked about symptoms they are experiencing and a
      series of verbal working memory tests will also be performed.
    

Intervention name(s): Diazoxide; Placebo
Intervention type(s): Drug; Drug
Intervention description(s): Diazoxide 7mg/kg, given 2 hours before the start of the clamp study; Lactose Ph capsules (Placebo)
Other intervention name(s): Eudemine (Diazoxide); Lactose Ph capsules (Placebo)
Intervention MeSH terms: Diazoxide
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Double (Participant, Investigator)
Primary purpose: Prevention
Keywords: Type 1 diabetes; Hypoglycaemia; Diazoxide