Clinical trial NCT04157738
Conditions: Diabetes Mellitus Type 1 Diabetes
Keywords: Diabetes Glycemic variability Insulin Parental Stress Advanced carbohydrates counting Insulin for meals
Sponsor: Emory University
Start date: 2019-11-27; Completion date: 2020-12-17
Enrollment: 24 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
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:
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.

Arms: arm 1: 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. arm 2: Children and adolescents with newly-diagnosed T1DM will receive an Insulin to carbohydrate ratio (ICR) with variable carbohydrate intake mealtime regimen
Interventions: intervention 1: Rapid-Acting Insulin intervention 2: Long acting insulin
Intervention descriptions: intervention 1: 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) intervention 2: Prior to discharge, all subjects will receive a regimen that includes a daily dose of long-acting insulin (Glargine)

Protocol documents:
Prot_SAP_000.pdf: 
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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 
 
Date: October 16, 2019. 
 
NCT # NCT04157738 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


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1. TITLE PAGE 
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. 
 
Eric I. Felner, MD, MS * 
Jacqueline V. Reyes Diaz, MD ** 
Courtney McCracken, PhD*** 
(*) Professor of Pediatrics, Division of Pediatric Endocrinology, Emory University. 
(**) Fellow, Pediatric Endocrinology, Emory University. 
(***) Pediatric Biostatistics Core, Department of Pediatrics, Emory University  
Version Date: October 16, 2019. 
 
2. EXTERNAL COLLABORATERS 
Not applicable 
 
3. ABSTRACT 
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 [1].  Prior to the 21st century, most individuals were treated 
with consistent carbohydrate intake and relatively set, or fixed doses of insulin [2].  Over nearly the past twenty 
years, with the availability of multiple rapid-acting and basal insulin analog preparations, individuals with 
diabetes have had the ability to utilize a variable carbohydrate and insulin regimen. These diabetics have the 
ability to eat as much or as little amount of food he/she desires, assuming he/she delivers an appropriate amount 
of rapid-acting insulin to cover the amount of carbohydrates. The insulin-to-carbohydrate ratio (ICR) is 
determined through trial-and-error as well as experience [3].  In addition to the use of the ICR, the management 
of diabetes for most children and adolescents requires consistent parental involvement and supervision [4].  
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.  
 
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. The objective of this investigator-initiated, 
prospective proposal is to determine if children and adolescents with T1DM have improved glycemic control 
and, their families experience less anxiety with a fixed insulin and carbohydrate regimen compared to those 
using an ICR and variable carbohydrate intake.  
 
4. BACKGROUND 
Type 1 diabetes mellitus (T1DM) is an autoimmune disorder characterized by a severe deficiency or absence 
of endogenous insulin, resulting in chronic hyperglycemia. The achievement of optimal glucose control is 
facilitated by intensive insulin treatment [5]. The current recommendations are based on the basal bolus 


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paradigm, with subcutaneous long-acting insulin or continuous subcutaneous infusion of rapid-acting insulin 
to cover basal requirements and with rapid-acting insulin to prevent or correct glucose excursions. Home blood 
glucose monitoring has been the mainstay for glucose monitoring for more than 30 years. It provides 
information about an individual’s glucose level and allows individuals to make adjustments as needed to help 
them manage their glycemic control [6].  
Despite advances in medical treatment and technology, nutritional therapy continues to be the cornerstone of 
diabetes management [7]. Carbohydrates are a major determinant of postprandial blood glucose. Carbohydrate 
counting is a meal planning approach that focuses on carbohydrates as the primary nutrient affecting 
postprandial glycemic response. Advanced carbohydrate counting allows adjustment of the prandial insulin 
dose for actual carbohydrate intake for diabetics using intensive insulin therapy. According to the Bell and 
Shimin meta-analysis, carbohydrate counting significantly reduced HbA1c concentration in adults [8,9]. 
Tascini et al reported that carbohydrate counting had a positive effect in children and adolescents with T1DM, 
by reducing hypoglycemic events and improving quality of life [5]. These studies, however, did not compare 
different types and amount of insulin for variable carbohydrate intake.  
 
Fixed mealtime carbohydrate with a fixed mealtime insulin dose 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. A 
set amount of carbohydrate is assigned in grams or portions and patients choose different carbohydrate servings 
to equal the target amount. This method is easy to use and may be appropriate for patients who are new to 
taking insulin in that it may improve compliance, glycemic control, and anxiety. 
Shortly after diagnosis of T1DM, many children and adolescents not uncommonly experience a honeymoon 
period [10]. It occurs because there is a sufficient amount of residual B-cell mass that enables some of these 
individuals to secrete some endogenous insulin. As a result, in order to prevent hypoglycemia, these individuals 
may be managed with less exogenous insulin over a short period of time [11]. This variability makes less 
accurate HbA1C concentration as a gold standard for assessing glucose control in the first 6-12 months after 
diagnosis [12,13]. 
Glycemic variability (GV) obtained from multiple blood glucose levels (up to 6 – 10 times/day) provides a 
good correlation for an individual’s glycemic control and predictor of chronic diabetic complications [3]. The 
GV refers to swings in blood glucose levels and captures blood glucose oscillations that occur throughout the 
day, including hypoglycemic periods, postprandial increases, as well as blood glucose fluctuations that occur 
at the same time on different days [14]. The proposed target range of 70–180 mg/ dl is considered acceptable 
for clinical practice, as it has been observed that if 50% of the self-monitoring of blood glucose readings are 
in this range, the A1C would be ~7% [12,13].  Shapiro et al, reported that teens and parents show some 
similarities in the facets comprising distress, including negative emotions about diabetes and the demanding 
diabetes regimen [15]. Simplified insulin treatments will remarkably help to maintain adherence and to prevent 
deterioration in glycemic control.  


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5. 
APPROACH –RESEARCH METHODS 
 
A. 
STUDY DESIGN 
Two - Arm, Randomized, Clinical trial (See Figure 1) 
 
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 and determine: 
 
1) Specific Aim 1 
Determine the feasibility for a subsequent clinical trial involving rapid acting insulin dosing for 
a fixed dose for fixed carbohydrates (FIXED group) vs ICR with variable carbohydrate intake 
(ICR group) in order to determine the capacity for recruitment, caregiver consent to random 
assignment and completion of study measures, average session attendance, caregiver treatment 
adherence, and post-treatment satisfaction. 
 
2) Specific Aims 2 
a) 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. 
 
b) 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.  
 
We hypothesize that we will recruit and consent enough patients in order to perform a future, 
larger trial where caregivers of children and adolescents with newly diagnosed T1DM using a 
fixed insulin for fixed carbohydrate mealtime regimen (FIXED group) will experience less 
anxiety and their diabetic children will experience less GV than children and adolescents with 
newly diagnosed T1DM who use an ICR with variable carbohydrate intake at mealtime (ICR 
group). If this proves to be true, less anxiety may encourage more compliance and better 
glycemic control.  
 
For the purposes of this study the following definitions will be used: 
 
BMI:  Weight (kg)/ Height (m2).  
Glycemic variability: Blood glucose oscillations that occur throughout the day. The glycemic range 
on target is between 80 – 180 mg/dl.  
Insulin dose adjustment: Titration of insulin over time to improve glycemic control.  
Parental stress: Stress associated to caring for a child with diabetes.   
Insulin to carbohydrate ratio (ICR): Number of carbohydrates that 1 unit of rapid-acting insulin 
covers.  
Basal insulin: Insulin that controls blood sugar consistently for 24 hours.  
Rapid-acting insulin: Mealtime insulin. Typically has onset in 10 - 15 minutes, peaks at 45 – 60 


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Figure 1: Study design and hypothesis. 
 
3) Methods 
 
a) Recruitment & Consent 
Subjects with newly diagnosed T1DM will be evaluated by authorized study personnel 
under a HIPAA waiver to determine potential eligibility. The subjects will be contacted 
by the research study team while in the hospital during his or her initial diagnosis to 
explore his/her interest in the study and to confirm eligibility. The informed 
consent/assent documents will be signed at the time of the initial contact. 
 
b) Initial Visit (at CHOA-Egleston) 
Recruitment of the 20 to 40 pediatric subjects will take place at the Children’s 
Healthcare of Atlanta at Egleston, when they are hospitalized with the diagnosis of new 
onset T1DM.  
Enrolled participants will be interviewed in order to collect demographic information. 
The subjects 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); 


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2) Evening 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. 
 
c) After Hospital Discharge and Between Clinic Visits 
 
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.  
 
d) Diabetes Clinic Visits 
 
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, undergo a physical examination, and objective data (vital signs, glucose meter 
(GM) data, insulin dosing, and carbohydrate intake) will be collected by the study 
personnel. 
 
 
B.  
STUDY POPULATION 
 
The plan is to enroll from 20 to 40 children and adolescent subjects with newly-diagnosed 
T1DM. Twenty will be randomized to the FIXED group and twenty will be randomized to the 
ICR group.  The subjects will be selected from children and adolescents admitted to CHOA-
Egleston with a diagnosis of new-onset Diabetes Mellitus. Participation in this study will be 
determined by a set of inclusion/exclusion criteria.  
 
1) Inclusion Criteria 
For enrollment in the study, subjects must: (1) Have Confirmed diagnosis of T1DM based on 
the most recent ADA criteria [16]; (2) Be 8 - 14 years of age; (3) Begin monitoring with a 
glucose monitor prior to discharge from the hospital; and (4) Have the ability to understand and 
be willing to adhere to the study protocol. (5) English or Spanish speakers.  
 
2) Exclusion criteria 
For enrollment in the study, subjects may not: (1) Have a clinically significant major organ 
system disease (i.e., hypertension, hyperlipidemia, or obesity); (2) Be on glucocorticoid 
therapy; (3) Have Type 2 Diabetes Mellitus; (4) Have Polycystic Ovarian Syndrome (PCOS); 
(5) Have a BMI > 85th %ile; (6) Have Acanthosis Nigricans; (7) Have any form of renal 
impairment; (8) Have Cystic Fibrosis; (9) Have Glucocorticoid-, Chemotherapeutic-, or any 
other Medication-induced form of Diabetes; (10) Be using any basal insulin other than Glargine 
insulin; (11) Have cognitive impairment (> 2 grades behind age-appropriate grade in school); 
(12) Be in Foster Care; (13) Have any history of DFCS involvement; and (14) If female, be 
pregnant or breast-feeding.  


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C.  
DATA MANAGEMENT 
 
All data, including patient demographics, history, and laboratory tests will be collected on 
standardized forms and entered into an electronic database, REDCap. REDCap is a HIPPA-
compliant, web-based, data capturing tool used in over 130 countries. Features include user-
specific credentials, data-logging, longitudinal data modeling and more.  Enrolled patients will 
be assigned a study ID. Subjects will only be identified in REDCap by their study ID. The 
patient’s name, MRN and study ID will be kept in a secure file in a double lock in a filing 
cabinet under Dr. Felner’s supervision in the Emory Children’s Center. Records will be 
maintained for 10 years as required for IRB studies. 
 
D. 
OUTCOME MEASURES 
 
1) Primary Outcome Measures 
 
The primary goal of this study is to determine the feasibility of a subsequent clinical trial of 
rapid acting insulin dosing for fixed carbohydrates (FIXED group) vs ICR with variable 
carbohydrate intake (ICR group). In doing so, we will examine our ability to recruit and consent 
patients (>70% consent rate), study retention (>90% retention), completion of study visits 
(average session attendance ≥ 90%), study measures (≥ 90% measure completion), caregiver 
treatment adherence, and post-treatment satisfaction (≥ 90%), 
 
2) Secondary Outcomes Measures 
 
Secondary outcome measures will include caregiver anxiety and glycemic variability. Each of 
these measures are described below. 
  
One secondary outcome measure is caregiver anxiety. This will be assessed by a parental stress 
scale [17]. The caregiver will fill out the questionnaire at initial enrollment (prior to hospital 
discharge) and at each clinic follow-up throughout the study. We will use the Spanish adaptation 
of parental stress scale (PSS) [18] for Spanish population if necessary. 
 
We clarify in the survey that the questions are to be answered in terms of how the caregiver-
child relationship exists since the diagnosis of diabetes mellitus. 
The scales are shown in Annex 1 and 2 
 
Glycemic variability (GV) is another secondary outcome measure. The GV will be calculated 
in all subjects through the use of a glucose monitor (GM) data classification scale. Subjects will 
be considered to have appropriate GV if their blood glucose level is in the range of 80 mg/dL – 
180 mg/dL (Group C).  
 
The GV classification is as follows: 
Group A: < 50 mg/dl. 
Group B: 50 – 79 mg/dl 
Group C: 80 – 180 mg/dl  
Group D: 181 – 350 mg/dl 
Group E: > 350 mg/dl 


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Safety is the last secondary outcome measure. The safety measured that will be compared in 
both groups include death, risk of life threatening event (i.e., severe hypoglycemia associated 
with seizure or altered mental status), hospitalization for diabetes complication (diabetic 
ketoacidosis or hypoglycemia), and risk of disability or permanent damage.  
 
E. 
STATISTICAL CONSIDERATIONS 
 
Randomization 
Randomization will be performed by study statistician using random-permuted blocks of size 2 
and 4. Randomization assignments will be placed in sealed, opaque envelopes to be stored. 
Study investigators will not be blinded to treatment assignment.  
 
Sample Size 
A goal of 20 patients is necessary for this study, but we will reach up to 40 participants in case 
there is any withdraw after consented and randomized. While the overall goal of the study is to 
demonstrate feasibility of a subsequent randomized controlled trial, limited efficacy testing will 
be performed. Given a sample size of 20 participants (10/grp), we will have greater than 90% 
power to detect a minimum standardized mean difference of 1.25 (i.e., approximately a 1.25 
standard deviation difference) between groups. Effect sizes will be calculated for all study 
measures of interest and be used in future power calculations.  On average, there are ~25 new 
type I/II diabetics diagnosed at Egleston hospital each month. Assuming an eligibility rate of 
40%, 10 patients would be eligible to participate each month. Based on this, we are confident 
in our capacity to recruit 20 to 40 participants during the study period with the goal of having 
20 participants to complete the study.  
 
Statistical Analysis 
Demographic characteristics will be summarized for both groups using means and standard 
deviations, medians and quartiles, or counts and percentages, as appropriate based on 
distribution. T-tests, Wilcoxon rank sums, and/or Chi squared tests will be used to assess 
differences between the two groups. 
 
Primary Aims: Measures of feasibility (consent, retention, engagement, satisfaction, etc.), will 
be summarized overall and by group, when applicable.  
 
Secondary Aim 1: Parental stress scale 
The parental stress scale will be scored per the instrument’s instructions. The total scores for 
the treatment groups will be compared in a cross-sectional fashion using t-tests or Wilcoxon 
rank sums tests as appropriate based on the distribution of scores. Changes in parental distress 
over-time will be evaluated using two-way repeated measures analysis of variance models. 
Models will include the main effect of treatment assignment, time (baseline, 1 month, 4 
months), and the treatment X time interaction. The interaction term will serve as the primary 
statistical test for aim 2. Summary statistics, statistical significance, and effect sizes will be 
reported by group at each time point of interest, when applicable.  
 
 
 


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Secondary Aim 2: Glycemic variability 
Glycemic variability will be examined both as a continuous variable and a categorical variable 
using the ranges defined in section D. Time series analysis will be used to examine daily 
measures of blood glucose (obtained from patient diary’s) during the study period. Variability 
will be measured as the probability of acute change (PAC), using methods described by Jahng 
et al. (2008). Acute changes will be adjusted for time between readings. In addition, first-order 
autocorrelations and/or mean-square successive difference will be used to examine variation in 
readings as described by Janhg. Multilevel modeling will be used to test between-group 
differences in variability. 
 
Secondary Aim 3: Safety 
 Adverse event of interest and serious adverse events (see section D) will be summarized overall 
and by treatment group. For participants experiencing more than 1 episode of a specific event 
(e.g., severe hypoglycemia), the maximum grade and severity will be recorded. Chi-square tests 
will be used to compare the frequency of events between the two cohorts.  
 
Given the exploratory nature of these secondary outcomes, we will calculate effect sizes based 
on the adjusted means and standard deviations or differences in proportions, when appropriate. 
 
All analyses will be conducted using SAS v9.4 (Cary, NC).  
 
F.  
ANTICIPATED RESULTS 
 
This research will be feasible to develop a successful larger clinical trial. Due to the fixed 
regimen seeming to be less complicated, because there are less calculations to make than in 
those using the ICR group, we anticipate that parental anxiety will be decreased in the FIXED 
group. This will encourage more blood glucose monitoring and treatment compliance. 
Therefore, we anticipate GV to be decreased for the FIXED group.  
 
G. 
LIMITATIONS 
 
The major limitations of this study are related to caregiver’s self-completion questionnaire and 
ability to contact study personnel frequently during the study period in order to report blood 
glucose levels and implement the insulin adjustments. More than likely, multiple insulin 
regimens should work, but the idea behind this study is that the fixed regimen may be easier to 
implement. 
 


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Figure 2: Proposed protocol. 
 
6. DATA COLLECTION FOR FUTURE RESEARCH 
Records will be maintained for 10 years as required IRB studies. 
 
7. COMMUNITY PARTICIPATION 
Not applicable  
 
8. PARTICIPATION SELECTION 
Study subjects will be selected from the cohort of pediatric patients with newly diagnosed of type 1 diabetes 
mellitus hospitalized at Children’s Health of Atlanta and followed at diabetes clinic in the Center for 
Advanced Pediatrics Georgia. Parents will consent and subjects will assent for the subject to enroll in the 
research study. 
 
9. INFORMED CONSENT 
During hospitalization for newly diagnosed of type 1 diabetes mellitus. The study will be initially 
discussed, parents and participants will be provided with a HIPAA compliance form and consent/assent 
form. 
 
10. INCIDENTAL FINDINGS 
Not applicable 
 
 


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11. COMPENSATION FOR TIME & EFFORT 
No monetary compensation will be provided to participants. Participants will not be charged for any of the 
research activities. 
 
12. DATA & SAFETY MONITORING PLAN (DSMP) 
There will not be an independently constituted data safety and monitoring board for this protocol because 
it does not involve an experimental intervention. Instead, this study will have a data safety and monitoring 
plan (DSMP). This plan includes examination of consent rates, attrition, and safety related data. The plan 
will be generated by the study statistician in conjunction with the PIs of the study. Presentation of data will 
be presented in a blinded fashion with treatments de-identified. The first DSMP will be reviewed after 12 
patients enroll in the study, then subsequently every 6 months of the study. There are no plans for an interim 
analysis as this is a pilot study. 
 
All relevant adverse events related with diabetes will be documented and reviewed by the principal 
investigator. These will be enumerated and reported according to IRB policies. Any serious adverse events 
will be reported within 24 hours to the IRB. They will be reviewed by all investigators and a disposition 
determined before proceeding with further enrollment. There are no additional laboratory evaluations 
outside of the routine care for patients with diabetes mellitus. 
 
The procedures associated with this research trial are associated with minimal risk. 
 
13. POTENTIAL BENEFITS 
Participation in this study offers appropriate plans that are well-established and have been utilized to help 
children and adolescents with T1DM maintain appropriate glycemic control. Although the research may 
not benefit the subject initially and directly, the results of the study could lead to develop bigger clinical 
trial to demonstrate alterations of current management options for children and adolescents with newly-
diagnosed T1DM.  
 
14. ADVERSE EVENTS & RISKS 
There are minimal risks associated with GM. A GM is a self-monitoring of blood sugars via finger-stick 
that help making treatment decisions about diabetes. There is a small possibility that the measurements 
may not be accurate. We will consider these factors that affect meter accuracy and the steps to resolve or 
prevent the problems like test strip problems (Be sure the strips are meant for the meter), keeping the 
glucose meter and test strips at extreme temperatures (Keep glucose meter at room temperature), improper 
test strip coding, problems inserting the test strip in the monitor or not enough blood applied to test strip 
(recommend a generous drop of blood to test strip). 
 
Regarding capillary sampling by finger-stick with a lancet, can carry a small risk of the following: 
infection, bleeding, pain or local skin irritations including redness, swelling, bruising, itching, scarring or 
skin discoloration. 
 
15. CONFIDENTIALITY 
The study will comply with HIPAA guidelines regarding confidentiality of participant data.  Privacy will 
be assured during the consent and study procedures.  During the consent process, potential subjects and 
their parents will be allowed time to review the informed consent document and ask a member of the 
research team all their questions regarding the research study. All questionnaires will be labeled with a 


12 
 
study ID. Data, including paper copies of participant data, original signed consent and HIPAA documents, 
completed questionnaires, and all source documents, will be stored in a medical building with card-coded 
access inside a locked cabinet. Data stored on the computer will be encrypted and password protected. A 
separate file will be kept on an encrypted and password protected computer that will contain participant 
identifiers linking names and contact information to the study for purpose of follow up in this clinical trial. 
This information will not be entered into the computer system for study data. At completion of study, all 
participants’ identifiable information will be stored at Access Data Management System for a period of 10 
years. After 10 years, all information will be destroyed. When papers are published regarding this study 
and data obtained, only composite data will be used, and each subject’s identity will be strictly protected. 
 
Although IRB policies to protect confidentiality of study information will be followed, it is possible that a 
breach could occur. The following steps will be taken to limit that possibility: 1) Source documents for the 
study will be stored either in the CHOA HER (Epic) or as hard copies in locked filing cabinets in a locked 
office at Center for Advanced Pediatrics, 2) All subjects will be assigned a study number and all study 
records will bear only that number for identification. The key for identifying individual subjects will only 
be available to study personnel.  
 
16. REFERENCES 
1. Shimin Fu, Linjun Li, Shuhua Deng, Liping Zan, Zhiping Liu. Effectiveness of advanced carbohydrate 
counting in type 1 diabetes mellitus: systematic review and meta-analysis.Sci. Rep.6,37067; doi: 
10.1038/srep37067 (2016). 
2. Jiansong ao, MSC; Heather R. Gilbertson, PHD, ADVAPD; Robyn Gray, CDE; et al. Improving the 
Estimation of Mealtime Insulin Dose in Adults with Type 1 Diabetes. The Normal Insulin Demand for 
Dose Adjustment (NIDDA) study. Diabetes Care 2011. 34(10):2146-2151.  
3. American Diabetes Association. 13. Children and adolescents: Standards of Medical Care in 
Diabetes—2019. Diabetes Care 2019;42(Suppl. 1):S148–S16 
4. Laffel  LMB, Vangsness  L, Connell  A, Goebel-Fabbri  A, Butler  D, Anderson  BJ. Impact of 
ambulatory, family-focused teamwork intervention on glycemic control in youth with type 1 diabetes. J 
Pediatr 2003;142:409–416 
5. Giorgia Tascini, Maria Giulia Berioli, Laura Cerquiglini, Elisa Santi, Giulia Mancini, Francesco 
Rogari, Giada Toni, Susanna Esposito. Carbohydrate Counting in Children and Adolescents with Type 
1 Diabetes. Nutrients. 2018 Jan; 10(1): 109. 
6. Leann Olansky MD; Laurence Kennedy MD. Finger-stick Glucose Monitoring. Diabetes Care. 2010; 
33(4):948-949. 
7. Smart C.E., Aslander-van de Vliet E., Waldron S. ISPAD Clinical Practice Consensus Guidelines 2009 
Compendium: Nutritional management in children and adolescents with diabetes. Pediatr. 
Diabetes. 2009;10:100–117.  
8. Shimin Fu, Linjun Li, Shuhua deng, Liping Zan, Zhiping Liu. Effectiveness of advanced carbohydrate 
counting in Type 1 diabetes mellitus: a systematic review and meta-analysis. Scientific reports, 14 
November 2016, Vol.6, pp.37067 
9. Bell, K. J., Barclay, A. W., Petocz, P., Colagiuri, S. & Brand-Miller, J. C. Efficacy of carbohydrate 
counting in type 1 diabetes: a systematic review and meta-analysis. Lancet Diabetes Endocrinol 2(2), 
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11. Sarafoglou,K; Hoffmann, G; Roth, K. Pediatric Endocrinology and Inborn Errors of Metabolism. 
Second Edition. 2017. p 310 - 326.  


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12. Vigersky RA, McMahon C. The Relationship of Hemoglobin A1C to Time-in-Range in Patients 
with Diabetes. Diabetes Technol Ther. 2019; 21(2):81-85. 
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Time in Range, Hypoglycemia, and Other Parameters. Diabetes Technology & Therapautics. 2017; 
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Important?. Diabetes Metab J. 2015; 39(4): 273-282. 
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Weissberg-Benchell, Jill. Psychometric Properties of the problem Areas in Diabetes: Teen and Parent 
of Teen Versions. Journal of pediatric psychology, 01 2018, Vol.43(5),pp.561-571 
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and Personal Relationships 1995; 12 (3):p. 463-472. https://doi.org/10.1177/0265407595123009 
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Psicothema. 2007; 19 (4): 687 -692. ISSN: 0214-9915  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


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Annex 1: Parental Stress Scale and Scoring.  
 
 
Parental Stress Scale  
The following statements describe feelings and perceptions about the experience of being a parent with a child 
with new onset type 1 diabetes mellitus. Think of each of the items in terms of how your relationship with your 
child typically is in the setting of recently diagnosis of diabetes mellitus. Please indicate the degree to which 
you agree or disagree with the following items by placing the appropriate number in the space provided. 
1 = Strongly disagree 2 = Disagree 3 = Undecided 4 = Agree 5 = Strongly agree  
1 
I am happy in my role as a parent 
2 
There is little or nothing I wouldn't do for my child(ren) if it was necessary. 
3 
Caring for my child(ren) sometimes takes more time and energy than I have to give.  
4 
I sometimes worry whether I am doing enough for my child(ren). 
 
5 
I feel close to my child(ren).  
6 
I enjoy spending time with my child(ren).  
 
7 
My child(ren) is an important source of affection for me. 
8 
Having child(ren) gives me a more certain and optimistic view for the future.  
9 
The major source of stress in my life is my child(ren). 
10 
Having child(ren) leaves little time and flexibility in my life. 
11 
Having child(ren) has been a financial burden. 
12 
. It is difficult to balance different responsibilities because of my child(ren).  
13 
The behavior of my child(ren) is often embarrassing or stressful to me. 
14 
If I had it to do over again, I might decide not to have child(ren). 
15 
I feel overwhelmed by the responsibility of being a parent.
16 
Having child(ren) has meant having too few choices and too little control over my life. 
17 
I am satisfied as a parent 
18 
I find my child(ren) enjoyable 
Scoring: 
To compute the parental stress score, items 1, 2, 5, 6, 7, 8, 17, and 18 should be reverse scored as follows: 
(1=5) (2=4) (3=3) (4=2) (5=1). The item scores are then summed. 
Scoring the tool: 
We want a low score to signify a low level of stress, and a high score to signify a high level of stress 
 
Overall possible scores on the scale range from 18 – 90. 
 
The higher the score , the higher the measured level of Parental stress 
Use a simple table to show the before and after results to evidence whether an intervention has had a positive 
effect.  
 
Comparison of individuals before / after or longitudinal overall Parental Stress Scale scores. 
 
The comparison of before and after mean average scores for groups (parents/care givers accessing the 
particular intervention/group sessions, service or provision). 
 


15 
 
Annex 2: Spanish version of Parental Stress Scale and Scoring.  
 
 
Escala de Estres Parental 
 
Las siguientes oraciones describen sentimients y percepciones acerca de como un padre/madre/cuidador se 
siente cuidando a un nino que ha sido diagnosticado con diabetes mellitus recientemente.  Responder cada 
pregunta pensando en como es la relacion entre su nino(a) con usted desde el diagnostico de diabetes mellitus.  
Indicar el grado de acuerdo o desacuerdo en cada una de las siguientes preguntas y coloque el numero 
apropiado en el espacio correspondiente.  
1 = Totalmente en desacuerdo  
2 = Desacuerdo  
3 = Indeciso  
4 = De acuerdo  
5 = Totalmente de acuerdo  
  
1 
Me siento feliz en mi papel como padre/madre
2 
No hay nada o casi nada que no haria por mi hijo/a si fuera necesario 
 
3 
Atender a mi hijo/a a veces me quita mas tiempo y energia de la que tengo.
4 
A veces me preocupa el hecho de si estoy hacienda lo suficiente por mi hijo/a 
 
5 
Me siento muy cercano/a a mi hijo/a 
6 
Disfruto pasando tiempo con mi hijo/a  
 
7 
Mi hijo/a es una fuente importante de afecto para mi 
8 
Tener un hijo/a me da una vision mas certera y optimista para el future
9 
La mayor fuente de estres en mi vida es mi hijo/a
10 
Tener un hijo/a deja poco tiempo y flexibilidad en mi vida.
11 
Tener un hijo/a ha supuesto una carga financiera
12 
Me resulta dificil equilibrar diferentes responsabilidades debido a mi hijo/a 
13 
El comportamiento de mi hijo/a menudo me resulta incomodo o estresante
14 
Si tuviera que hacerlo de Nuevo, podria decider no tener un hijo/a 
15 
Me siento abrumado/a por la responsabilidad de ser padre/madre 
 
16 
Me siento satisfecho/a como padre/madre 
17 
Disfruto de mi hijo/a  
Scoring: 
Participants will be asked to rate each one on a 1-to-5 Likert-type response scale ranging from 1 (strongly 
disagree [totalmente en desacuerdo]) to 5 (strongly agree [totalmente de acuerdo]). The items appeared in 
the same order as in the English-language PSS (except for the eliminated item 16 in the English version.). 
The total score was obtained by summing up the value for each item (reversed items are 1, 2, 5, 6, 7, 8, 16, 
and 17). A higher score indicates a higher level of parental stress.