Feasibility Study of the Effect of Intra-Dermal Insulin Injection on Blood Glucose Levels After Eating

Study Overview
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Brief Summary
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This study is to determine the effect of intra-dermal (ID) administration of regular and of rapid-acting insulin, before eating, on blood glucose levels for several hours after a standard meal (a mixed, liquid meal). Insulin will also be given normally, subcutaneously, for control or comparison purposes. The hypothesis or expectation is that ID insulin will work more quickly and control blood glucose levels better than SC injection.

Detailed Description
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Previous studies have shown that intra-dermal (ID) insulin administration results in a more rapid onset of action in comparison to subcutaneous (SC) administration as measured by glucose infusion rate (GIR) under glucose clamp conditions.The aim of this study is to investigate whether ID administration of regular human insulin or rapid-acting insulin analogue leads to reduced postprandial glycemic excursions in comparison to SC application under highly standardized experimental conditions. Effects on the occurrence of hypoglycemia will also be investigated, as well as pK and pD comparisons between different insulin formulations administered ID. This is a mono-center, open-label, randomized, 5-period crossover study in patients with type 1 diabetes

Official Title
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A Mono Center Open Labeled, Randomized Study Examining the Effects of Intra-Dermal vs Subcutaneous Application of Regular Insulin or Rapid Acting Insulin Analogue on Postprandial Glycemic Excursions in Patients With Type 1 Diabetes

Conditions
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Diabetes Mellitus, Type 1

Intervention / Treatment
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* Drug: Regular insulin (Humulin)
* Drug: Insulin lispro (Humalog)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Type 1 diabetes for 1-15 years, on multiple daily injections (MDI) or insulin pump (CSII) in stable control with HbA1c <= 9.0%. Able to attend clinic for 5 different days Exclusion Criteria: BMI > 32 kg/m2 Evidence of gastroparesis or impaired renal function or lipodystrophy

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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Male

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: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: 1<br>Regular insulin SC at -17 mins | Drug: Regular insulin (Humulin)<br>* Insulin will be given either subcutaneously or intra-dermally, and at two different times prior to the liquid meal (T zero). At -17 mins, regular insulin will be given either SC or ID. At -2 mins, regular insulin will be given ID; also insulin lispro will be given either SC or ID. Each patient will receive 1 injection on 5 different study days.<br>|
| Active Comparator: 2<br>Regular insulin ID at -17 mins | Drug: Regular insulin (Humulin)<br>* Insulin will be given either subcutaneously or intra-dermally, and at two different times prior to the liquid meal (T zero). At -17 mins, regular insulin will be given either SC or ID. At -2 mins, regular insulin will be given ID; also insulin lispro will be given either SC or ID. Each patient will receive 1 injection on 5 different study days.<br>|
| Active Comparator: 3<br>Regular insulin ID at -2 mins | Drug: Regular insulin (Humulin)<br>* Insulin will be given either subcutaneously or intra-dermally, and at two different times prior to the liquid meal (T zero). At -17 mins, regular insulin will be given either SC or ID. At -2 mins, regular insulin will be given ID; also insulin lispro will be given either SC or ID. Each patient will receive 1 injection on 5 different study days.<br>|
| Active Comparator: 4<br>Insulin lispro given SC at -2 mins | Drug: Insulin lispro (Humalog)<br>* Insulin will be given either subcutaneously or intra-dermally, and at two different times prior to the liquid meal (T zero). At -17 mins, regular insulin will be given either SC or ID. At -2 mins, regular insulin will be given ID; also insulin lispro will be given either SC or ID. Each patient will receive 1 injection on 5 different study days.<br>|
| Experimental: 5<br>Insulin lispro given ID at -2 mins | Drug: Insulin lispro (Humalog)<br>* Insulin will be given either subcutaneously or intra-dermally, and at two different times prior to the liquid meal (T zero). At -17 mins, regular insulin will be given either SC or ID. At -2 mins, regular insulin will be given ID; also insulin lispro will be given either SC or ID. Each patient will receive 1 injection on 5 different study days.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area Under Curve (AUC) of the blood glucose (BG) profile after the meal, with and without baseline correction. |  | 90 mins | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximal BG (BGmax) |  | Approximately 4 hours per injection | 
| Total BG-AUC0-4 h |  | Approximately 4 hrs per injection | 
| Minimal BG (BGmin, time to BGmin (tBGmin) |  | Approximately 4 hrs per injection | 
| Insulin pharmacokinetics |  | Approximately 4 hrs per injection | 
| Number and seriousness of adverse events |  | Approximately 4 hrs per injections | 
| Vital signs, examination of insulin application |  | Approximately 4 hrs per injection | 
| Time to BGmax (tBGmax) |  | Approximately 4 hours per injection | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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diabetes, insulin, subcutaneous, intra-dermal, blood glucose