Diluted Insulin in Young Children: Bigger Volumes for Smaller Patients
Primary Purpose
Type1diabetes
Status
Completed
Phase
Early Phase 1
Locations
United States
Study Type
Interventional
Intervention
Aspart insulin
Sponsored by
About this trial
This is an interventional other trial for Type1diabetes
Eligibility Criteria
Inclusion Criteria:
- T1D of at least 6 months' duration
- Aged 9-15 years
- Continuous subcutaneous insulin therapy for at least 1 month;
- HbA1c ≤ 10%
- Normal hematocrit
- Able to give consent
Exclusion Criteria:
- Admission for DKA during the past 4 weeks
- Severe hypoglycemia during the past 4 weeks
- Other conditions/medications affecting insulin sensitivity (e.g. metformin)
Sites / Locations
- Yale University School of Medicine
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
Experimental
Arm Label
Aspart-U100 Insulin
Aspart-U25 Insulin
Arm Description
Standard Concentration Rapid Acting Insulin
Diluted Concentration of Rapid Acting Insulin
Outcomes
Primary Outcome Measures
maximum insulin concentration
maximum insulin concentration
Secondary Outcome Measures
Time to peak insulin concentration
Time to peak insulin concentration
Mean Glucose Infusion Rate (GIR)
Mean Glucose Infusion Rate
GIR Max
Glucose Infusion Rate Maximum
Time to GIR Max
Time to Glucose Infusion Rate Maximum
Full Information
NCT ID
NCT03666065
First Posted
September 7, 2018
Last Updated
August 9, 2023
Sponsor
Yale University
Collaborators
Juvenile Diabetes Research Foundation
1. Study Identification
Unique Protocol Identification Number
NCT03666065
Brief Title
Diluted Insulin in Young Children: Bigger Volumes for Smaller Patients
Official Title
Diluted Insulin in Young Children: Bigger Volumes for Smaller Patients
Study Type
Interventional
2. Study Status
Record Verification Date
August 2023
Overall Recruitment Status
Completed
Study Start Date
January 1, 2020 (Actual)
Primary Completion Date
June 30, 2023 (Actual)
Study Completion Date
June 30, 2023 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Yale University
Collaborators
Juvenile Diabetes Research Foundation
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
The aim of this study is to compare the pharmacokinetic (PK) profile of diluted insulin aspart (U25) with undiluted insulin aspart (U100) in school-aged children and adolescents with type 1 diabetes (T1D) utilizing the euglycemic clamp technique and a standardized meal in a controlled research environment.
The investigators hypothesize that dilution of insulin aspart (U25) will alter the PK properties as compared to undiluted aspart.
Detailed Description
Study Design: participants age 9-15 y/o will be enrolled in a randomized cross-over trial, in which each participant will undergo two 24-hour admissions. Each admission will include a meal-study on the evening of admission followed by a euglycemic clamp study performed the following morning. During one of the admissions, participants will use undiluted insulin aspart (U100) while on the other the participants will receive diluted insulin aspart (U25).
(Figure 1)
Participants. 12 participants will be recruited between the ages of 9-15 years, who have had diabetes for at least 6 months' duration, on continuous subcutaneous insulin therapy for at least 1 month and have an HbA1c ≤ 10%. Those with a history of diabetes ketoacidosis (DKA) or severe hypoglycemia in the month prior to enrollment and those with other conditions/medications affecting insulin sensitivity (e.g. metformin) will be excluded from the study.
Study drugs: Diluted insulin U25 will be formulated by adding diluent, which will be obtained from Novo Nordisk, with insulin aspart. The diluted insulin will be formulated by the investigational pharmacy.
Study procedures:
Enrollment Visit: The study will be explained to potential participants who meet eligibility criteria and informed consent will be obtained. Demographic data will be recorded and history and physical exam will be performed. HbA1c, hematocrit and urine pregnancy tests in female participants who could become pregnant will be measured to confirm eligibility. Participants will be randomized for the first admission to either diluted insulin studies followed by a second admission for undiluted insulin studies or vice versa.
1st Inpatient Standard Meal Study and Euglycemic Clamp Study: Participants will be admitted to the research unit in the afternoon on the day before the clamp procedure. The participants will be asked to change their infusion set and use the insulin provided for the study procedures- either the diluted or standard concentration insulin, based on randomization at enrollment. On the admission with diluted insulin, pump settings will be adjusted to account for the dilution (increased by a factor of 4 for basal rates, correction factors, and carbohydrate ratios). An intravenous catheter will be inserted into antecubital vein for blood sampling. Once the IV is placed, Yellow Springs Instrument (YSI) glucose values and insulin levels will be obtained at least every half hour.
At dinner (~6p.m.), participants will receive a meal prepared in the metabolic kitchen to allow for accurate determination of carbohydrate, fat and protein content. Participants will be asked to estimate the carbohydrate content of the meal prepared by the metabolic kitchen. The participant will bolus just prior to the start of the meal based on the carbohydrates estimated and the pre-meal glucose levels.
Glucose will be measured by YSI and aspart levels will be measured using the Mercodia iso-insulin enzyme-linked immunosorbent assay. Samples will be taken before the meal and every 10 minutes after the start of the meal for the first hour, every 15 minutes for the second hour, and then every 30 minutes for up to 4 hours after the bolus; namely, at 0, 10, 20, 30, 40, 50, 60, 75, 90, 105, 120, 150, 180, 210, and 240 minutes.
Participants will then have YSI glucose levels obtained at least every hour overnight with titration of insulin doses as needed to achieve targeted control (goal 80-140mg/dL) by 8a.m. A second IV line will be placed for glucose infusion. Once IV access is established and glucose is in the target range, the euglycemic clamp study will be initiated.
Prior to the start of the clamp, -15 and 0 minute samples will be obtained for baseline plasma glucose and insulin levels.
At time zero, a bolus of 0.1 U/kg will be administered via the pump. After administration of the bolus, the insulin pump will be disconnected. Plasma aspart insulin will be measured every 10 minutes for the first 120 minutes and then every 15 minutes for up to 240 minutes using the Mercodia iso-insulin enzyme-linked immunosorbent assay. Plasma glucose will be measured at least every 5 minutes for the duration of the clamp study, which will allow for titration of the glucose infusion rate to maintain euglycemia (target 90 +/- 10mg/dL).
Following completion of the clamp, the participant will be offered a meal and discharged home with standard concentration insulin and their usual pump settings.
2nd Inpatient Standard Meal Study and Euglycemic Clamp Study: Participants will return for a second admission after a minimum of 7 days since the first study.
The participant will receive whichever concentration of insulin not received during their first admission (ie. If first admission is diluted, then second admission will be standard concentration and vice versa).
The remainder of the study procedures are as indicated above. Following completion of the second clamp study, participants will have completed all study related procedures.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Type1diabetes
7. Study Design
Primary Purpose
Other
Study Phase
Early Phase 1
Interventional Study Model
Crossover Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
3 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Aspart-U100 Insulin
Arm Type
Active Comparator
Arm Description
Standard Concentration Rapid Acting Insulin
Arm Title
Aspart-U25 Insulin
Arm Type
Experimental
Arm Description
Diluted Concentration of Rapid Acting Insulin
Intervention Type
Drug
Intervention Name(s)
Aspart insulin
Other Intervention Name(s)
Standard Concentration insulin
Intervention Description
Standard insulin
Primary Outcome Measure Information:
Title
maximum insulin concentration
Description
maximum insulin concentration
Time Frame
240 minutes
Secondary Outcome Measure Information:
Title
Time to peak insulin concentration
Description
Time to peak insulin concentration
Time Frame
240 minutes
Title
Mean Glucose Infusion Rate (GIR)
Description
Mean Glucose Infusion Rate
Time Frame
240 minutes
Title
GIR Max
Description
Glucose Infusion Rate Maximum
Time Frame
240 minutes
Title
Time to GIR Max
Description
Time to Glucose Infusion Rate Maximum
Time Frame
240 minutes
10. Eligibility
Sex
All
Minimum Age & Unit of Time
9 Years
Maximum Age & Unit of Time
15 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
T1D of at least 6 months' duration
Aged 9-15 years
Continuous subcutaneous insulin therapy for at least 1 month;
HbA1c ≤ 10%
Normal hematocrit
Able to give consent
Exclusion Criteria:
Admission for DKA during the past 4 weeks
Severe hypoglycemia during the past 4 weeks
Other conditions/medications affecting insulin sensitivity (e.g. metformin)
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jennifer Sherr, MD
Organizational Affiliation
Yale University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Yale University School of Medicine
City
New Haven
State/Province
Connecticut
ZIP/Postal Code
06520
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
No
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Diluted Insulin in Young Children: Bigger Volumes for Smaller Patients
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