Prevention of Severe Hypoglycemia in Type 1 Diabetes

Study Overview
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Brief Summary
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Severe hypoglycaemia leading to collapse without warning is one of the most-feared complications for those with Type 1 diabetes. The aim of this study is to determine whether detection and targeted prevention of hypoglycaemia by using either an optimised subcutaneous insulin regime or continuous insulin regime can restore hypoglycaemia awareness in Type 1 diabetes. Following a 6-day continuous subcutaneous monitor glucose profile, participants will be randomised to 1 of 3 interventions: rigorous avoidance of hypoglycaemia on current insulin regime; targeted optimisation of subcutaneous insulin regime to avoid hypoglycaemia; or continuous subcutaneous insulin infusion. Symptomatic experience and severity of hypoglycaemia, pattern of hypoglycaemia on glucose profiling and, in selected individuals, response to hyperinsulinaemic hypoglycaemic clamp, will be compared over a 6 month period. It is envisaged that successful prevention of hypoglycaemia by one or more interventions may reverse altered hypoglycaemia awareness and prevent further episodes of severe hypoglycaemia.

Detailed Description
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The unifying objective of the proposed unblinded randomized prospective study is to determine whether hypoglycaemia awareness in Type 1 diabetes can be restored by rigorous avoidance of hypoglycaemia addressed by one of the following interventions: A non-targeted approach whereby pre-prandial glycaemic targets are raised from 4.5-7mmol/L to 7.2-8.3mmol/L and hypoglycaemia is rigorously avoided without specific alterations in subcutaneous insulin regime5 Optimisation of subcutaneous insulin regime employing pre-prandial short-acting insulin analogue in combination with once daily insulin Glargine targeted to prevent periods of hypoglycaemia identified by 24 hour glucose profiles Insulin delivery by external pump (continuous subcutaneous insulin infusion) targeted to prevent periods of hypoglycaemia identified by 24 hour glucose profiles

Official Title
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Can Hypoglycaemia Awareness Be Restored in Individuals With Type 1 Diabetes and Severe Hypoglycaemia Employing Optimised Subcutaneous Insulin Regime or Continuous Subcutaneous Insulin Infusion Pump

Conditions
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Type 1 Diabetes Mellitus

Intervention / Treatment
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* Drug: insulin glargine
* Device: continuous subcutaneous insulin infusion


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: type 1 diabetes recurrent severe hypoglycemia within the preceding 6 months attending the Newcastle Diabetes Centre Exclusion Criteria: previous use of rapid- and long-acting insulin analogs used in an multiple daily insulin injection regimen previous use of continuous subcutaneous insulin infusion pump alcohol or drug abuse seizures unrelated to hypoglycemia.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 74 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: insulin glargine|nan|
|Device: continuous subcutaneous insulin infusion|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| prevention of severe hypoglycemia |  |  | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| incidence of mild symptomatic hypoglycemia |  |  | 
| HbA1C |  |  | 
| Continuous Subcutaneous Glucose Monitoring System profiles |  |  | 
| Altered Hypoglycemia Awareness survey |  |  | 
| Hypoglycemia Fear Survey |  |  | 
| Diabetes Quality Of Life of questionnaires. |  |  | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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CSII, insulin analog, severe hypoglycaemia, altered hypoglycaemia awareness, diabetes quality of life, CGMS