Post-meal Insulin Dosing With Adjuvant Pre-meal Pramlintide in Children With Type 1 Diabetes Mellitus

Study Overview
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Brief Summary
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The primary objective of this study is to examine the effect of pramlintide given pre-meal and insulin given just after a meal vs. standard therapy of pre-meal insulin on post-prandial glucose excursions. The secondary objective is to examine the effect of pramlintide and insulin on glucagon suppression in type 1 diabetes.

Detailed Description
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Following approval by the Institutional Review Board at Baylor College of Medicine 8 adolescents (6 males, 2 females) with type 1 diabetes were recruited to the open-labeled, non-randomized, crossover study. Two male subjects were African American; the remaining subjects were all Caucasian. Six subjects were on insulin pump therapy, and the two on insulin glargine, self-administered at -90minutes. Subjects had their last meal before 12 midnight, and stayed at our research center from 7AM until completion of the study at 2PM. Study A was done before study B. Basal insulin doses of the subjects were kept constant through studies A and B. No subject was prescribed pramlintide any time in the past prior to participation in this study. Study A:Insulin therapy was continued as per prescribed home regimen without pramlintide. Subjects self-administered a rapid-acting insulin analog (aspart or lispro) bolus based on their individual insulin: carbohydrate ratio, following which they received 12oz (591ml) of Boost High Protein drink (360 calories, 50gms carbohydrate, 12 gms fat) at 9AM (0 minutes). The Boost was consumed in 5 - 7 minutes. Blood samples were collected for the analysis of blood glucose (BG) levels at -60, -30, -10, and 0 minutes, and every 10 minutes thereafter for the first hour, every 20 minutes for the second hour, and every 30 minutes until the study ended. Blood samples were also collected throughout the study at multiple time points for the analysis of insulin and glucagon levels. Subjects were provided with lunch at 2PM, and discharged. Study B:The study protocol was identical to study A except 30mcg of pramlintide was administered subcutaneously immediately prior to drinking the Boost at 9AM, and no insulin was given before the meal but was given 15 minutes after the meal (9:15AM) and the dose was reduced by 20%. Study B was conducted within 3 to 4 weeks of study A.

Official Title
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Reducing Postprandial Hyperglycemia With Adjuvant Premeal Pramlintide and Postmeal Insulin in Children With Type 1 Diabetes Mellitus.

Conditions
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Type 1 Diabetes Mellitus

Intervention / Treatment
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* Drug: Insulin
* Drug: Pramlintide + Insulin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Type 1 diabetes only Diagnosed with T1DM for at least 1 year HbA1C less than or equal to 8.5% Currently treated using insulin glargine with or without Humalog/ Novolog or on the insulin pump Hemoglobin equal to or greater than 12mg/dL Otherwise healthy, EXCEPT for T1DM and treated hypothyroidism Negative pregnancy test, in the case of females Exclusion Criteria: Lack of supportive family Evidence or history of chemical abuse BMI (body mass index) greater than the 90th percentile OR less than the 10th percentile for age Patient who is poorly compliant with current insulin management and/or Prescribed self blood glucose monitoring Patient who experiences recurrent severe hypoglycemia episodes (requiring assistance/ hospitalizations) in the past 6 months Have hypoglycemia unawareness Have a confirmed diagnosis of gastroparesis, and/ or require medications that stimulate gastrointestinal motility Pregnant or lactating patients, or patients planning on becoming pregnant

Ages Eligible for Study
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Minimum Age: 12 Years
Maximum Age: 21 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: Non-Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Rapid acting Insulin therapy - before meal<br>Insulin therapy was continued as per prescribed home regimen without pramlintide. Subjects self-administered a rapid-acting insulin analog (aspart or lispro) bolus based on their individual insulin: carbohydrate ratio, before meal | Drug: Insulin<br>* Insulin therapy was continued as per prescribed home regimen without pramlintide. Subjects self-administered a rapid-acting insulin analog (aspart or lispro) bolus based on their individual insulin: carbohydrate ratio, before meal.<br>* Other names: aspart or lispro;|
| Experimental: Pre-meal Pramlintide and Post-meal Insulin therapy<br>30mcg of pramlintide was administered subcutaneously immediately prior to the meal and insulin was given 15 minutes after the meal. The dose of insulin was reduced by 20%. | Drug: Pramlintide + Insulin<br>* 30mcg of pramlintide was administered subcutaneously immediately prior to the meal and insulin was given 15 minutes after the meal. The dose of insulin was reduced by 20%.<br>* Other names: Pramlintide Acetate;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Assess the Mean Area Under the Curve (AUC) for Blood Glucose Concentration in Subjects Treated With Pramlintide + Insulin, Compared to Insulin Alone | Blood glucose concentration in terms of mean AUC (0 to 240 minutes) was determined in subjects treated with Pramlintide + Insulin vs. Insulin alone | 0 to 240 minutes post-dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Measure of Glucagon Concentration in Subjects Treated With Pramlintide + Insulin, Compared to Insulin Alone. | Glucagon concentration in terms of mean AUC (0 to 120 minutes) was determined in subjects treated with Pramlintide + Insulin vs. Insulin alone | 0 to 120 minutes post-dose | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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pediatric, juvenile, diabetes mellitus, Pediatric type 1 diabetes mellitus