Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT03666065 |
| Other study ID # |
2000023577 |
| Secondary ID |
5-ECR-2014-112-A |
| Status |
Completed |
| Phase |
Early Phase 1
|
| First received |
|
| Last updated |
|
| Start date |
January 1, 2020 |
| Est. completion date |
June 30, 2023 |
Study information
| Verified date |
August 2023 |
| Source |
Yale University |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial 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.
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:
1. 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.
2. 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.
3. 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.
