A Study of Rapid-Acting Mealtime Insulin in Children and Adolescents With Newly Diagnosed Type 1 Diabetes Mellitus

Study Overview
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Brief Summary
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Type 1 diabetes mellitus (T1DM) is a challenging medical disorder, especially in children and adolescents. In order to prevent the chronic complications of hyperglycemia, the maintenance of near-normal glycemic control must be balanced with minimizing hypoglycemia. Although many pediatric endocrinologists provide an ICR plan for their newly diagnosed patients with T1DM, fixed dosing and other forms of insulin delivery are available. This proposal is designed to compare children and adolescents with newly diagnosed T1DM using a fixed insulin dose for fixed carbohydrate mealtime regimen (FIXED group) to children and adolescents with newly diagnosed T1DM using an ICR with variable carbohydrate intake (ICR group) mealtime regimen. In addition to determining the feasibility for a subsequently larger clinical trial, the aims of this investigator-initiated, prospective proposal, is twofold. The first is to determine if the caregivers of diabetics using a fixed insulin for fixed carbohydrate regimen (FIXED group) experience less anxiety than the caregivers of those using an ICR with variable carbohydrate intake regimen (ICR group) at 1- and 4-months post-randomization. The second is to determine if diabetics utilizing a fixed insulin for fixed carbohydrate regimen (FIXED group) have decreased glycemic variability (GV) than those using an ICR with variable carbohydrate intake regimen (ICR group) at 1- and 4-months post-randomization.

Detailed Description
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Although children and adolescents with T1DM have much more freedom with the amount of food (carbohydrates) they eat while using an ICR at mealtime, the difficulty in determining the amount of insulin needed, how and when to adjust the ICR, the difficulty with understanding the basics of managing T1DM, and the adaptation to a new lifestyle with T1DM may be more complicated than utilizing a simple plan that includes a fixed amount of insulin and fixed number of carbohydrates, at least for the first few months after diagnosis. As complicated as it is for children, adolescents, and their caregivers to learn how to manage T1DM after being discharged home in usually < 48 hours after diagnosis, a more simplified insulin regimen at mealtime may provide the family of and the child or adolescent with newly diagnosed T1DM with less stress and anxiety while still maintaining adequate glycemic control. Twenty - 40 subjects will be recruited at Children's Hospital of Atlanta (CHOA) at Egleston and will be randomized to either the FIXED group or the ICR group according to a computer-generated random sampling table. The subject and his/her caregivers will receive diabetes education while in the hospital in standard fashion. The subject and his/her caregivers will receive glucose monitoring education and training prior to hospital discharge. The subject and his/her caregivers will also receive a paper log to record the blood sugars, number of carbohydrates consumed and insulin administered at each meal throughout the day. Prior to discharge, all subjects will receive a regimen that includes a: 1) Meal-time insulin and carbohydrate regimen (# of units of insulin, # of carbohydrates, and/or ICR); 2) Daily dose of Glargine; 3) Hyperglycemia correction regimen for blood glucose levels > 199 mg/dL; and 4) Hypoglycemia treatment regimen for blood glucose levels < 70 mg/dL and/or symptomatic. As per standard diabetes care, caregivers will report all blood glucose levels every day (to the study investigators) until the subject's initial clinic visit 4-6 weeks after diagnosis. All insulin adjustments will be made by the study investigators. After the subject's first clinic visit, caregivers will contact the study investigators once a week to report blood glucose levels and the investigators will make adjustments as needed. All the diabetes clinic visits will occur at the Center for Advanced Pediatrics (CAP), approximately three miles from CHOA-Egleston Hospital. Subjects will attend clinic with one or more of the investigators approximately 1 and 4 months after enrollment. At each clinic visit, subjects (and their caregivers) will answer standard diabetes questions, subjects will undergo a physical examination, and subjects' objective data (vital signs, glucose meter (GM) data, insulin dosing, and carbohydrate intake) will be collected by the study personnel.

Official Title
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Fixed Dose for Fixed Carbohydrates vs. Variable Dosing for Variable Carbohydrates: A Study of Rapid-Acting Mealtime Insulin in Children and Adolescents With Newly Diagnosed Type 1 Diabetes Mellitus.

Conditions
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Diabetes Mellitus, Type 1 Diabetes

Intervention / Treatment
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* Drug: Rapid-Acting Insulin
* Drug: Long acting insulin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Have Confirmed diagnosis of T1DM based on the most recent ADA criteria Be 7 - 15 years of age Begin monitoring with a glucose monitor prior to discharge from the hospital Have the ability to understand and be willing to adhere to the study protocol English or Spanish speakers Exclusion Criteria: Have a clinically significant major organ system disease Be on glucocorticoid therapy Have Type 2 Diabetes Mellitus Have Polycystic Ovarian Syndrome (PCOS) Have a BMI > 85th %ile Have Acanthosis Nigricans Have any form of renal impairment Have Cystic Fibrosis Have Glucocorticoid-, Chemotherapeutic-, or any other Medication-induced form of Diabetes Be using any basal insulin other than Glargine insulin Have cognitive impairment (> 2 grades behind age-appropriate grade in school) Be in Foster Care Have any history of Division of Family and Children Services (DFCS) involvement If female, be pregnant or breast-feeding.

Ages Eligible for Study
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Minimum Age: 7 Years
Maximum Age: 15 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

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Fixed Group<br>Children and adolescents with newly-diagnosed T1DM will receive a fixed mealtime carbohydrate with a fixed mealtime insulin dose, that is a simplified regimen that provides a set amount of insulin for a set amount of carbohydrates, and ensures that each dose and each meal is consistent. | Drug: Rapid-Acting Insulin<br>* Prior to discharge, all subjects will receive a regimen that includes a Meal-time insulin and carbohydrate regimen (number of units of insulin, number of carbohydrates, and/or ICR)<br>* Other names: Lispro, Aspart, glulisine;Drug: Long acting insulin<br>* Prior to discharge, all subjects will receive a regimen that includes a daily dose of long-acting insulin (Glargine)<br>* Other names: Glargine;|
| Active Comparator: Insulin to carbohydrate ratio (ICR) Group<br>Children and adolescents with newly-diagnosed T1DM will receive an Insulin to carbohydrate ratio (ICR) with variable carbohydrate intake mealtime regimen | Drug: Rapid-Acting Insulin<br>* Prior to discharge, all subjects will receive a regimen that includes a Meal-time insulin and carbohydrate regimen (number of units of insulin, number of carbohydrates, and/or ICR)<br>* Other names: Lispro, Aspart, glulisine;Drug: Long acting insulin<br>* Prior to discharge, all subjects will receive a regimen that includes a daily dose of long-acting insulin (Glargine)<br>* Other names: Glargine;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of All Consented Participants | The capacity for recruitment was assessed, including all subjects that signed the Informed Consent Form (ICF). | 4 months post-intervention | 
| Number of Participants That Completed All Visits | Number of participants that were able to complete all study visits, including the visits in-person at 1 month and 4 months post-randomization. | 4 months post-intervention | 
| Caregiver Treatment Adherence at 1 Month and 4 Months Post-intervention | Caregiver treatment adherence was assessed using a blood glucose log. Subjects and caregivers recorded blood glucose levels and the amount/type of insulin given. This data was used to calculate adherence as a percentage ranging from 0% (no adherence) to 100% (full adherence). | 1 month post-intervention and 4 months post-intervention | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Caregiver Anxiety | Caregiver anxiety was measured with the parental stress scale. Caregivers completed the parental stress scale at initial enrollment and at each clinic follow up visit. The Parental Stress Scale includes 18 questions that are rated from 1 (strongly disagree) to 5 (strongly agree). Scoring ranges from 18 - 90. The higher the score, the higher the stress and anxiety level. | Baseline, 1 month post-intervention, 4 months post-intervention | 
| Glycemic Variability (GV) at 1 Month and 4 Months Post-intervention | The GV was calculated in all subjects using the average blood glucose levels collected from the daily blood glucose paper log. A subjective qualification system was used to label each subject's GV based on their blood glucose levels and an established glucose monitoring (GM) data system. Subjects are considered to have appropriate GV if their blood glucose levels are in the range of 80 mg/dL - 180 mg/dL. Percentage of participants within each specific average BG range is shown. | 1 month post-intervention, 4 months post-intervention | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Diabetes, Glycemic variability, Insulin, Parental Stress, Advanced carbohydrates counting, Insulin for meals