Type 1 Diabetes
Conditions
Keywords
Pharmacokinetics
Brief summary
The investigators are doing this research study to compare the pharmacokinetics (PK) (rate of absorption) of insulin lispro (Humalog), insulin aspart (Novolog), and insulin glulisine (Apidra) within individual subjects. Additionally, the investigators will perform a preliminary feasibility evaluation of a minimally invasive continuous insulin monitoring (CIM) device and its use to derive PK parameters in human subjects.
Interventions
OTHERMultiplex pharmacokinetic profiling
OTHERContinuous insulin monitoring
Sponsors
Massachusetts General Hospital
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
All subjects participated in the single arm of the study. Some subjects participated in the continuous insulin monitoring sub-study in addition to the main protocol, or separate from the main protocol.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Age 18 years or older with clinical type 1 diabetes for at least five years * Diabetes managed using an insulin infusion pump and rapid- or very-rapid-acting insulins including insulin aspart (NovoLog), insulin lispro (Humalog), and insulin glulisine (Apidra). * Ability to consume a sufficient amount of carbohydrates over 2-3 hours to cover 9 units of rapid acting insulin
Exclusion criteria
* Unable to provide informed consent * Unable to comply with study procedures * Inadequate venous access as determined by study nurse or physician at time of screening. * Pregnancy * History of gastric banding, gastric bypass, or other gastrointestinal condition that may prevent a subject from consuming a normal sized meal * Hemoglobin \<13.5 for men, \< 12 for women
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| For Multiplex PK Profiling: Aggregate Mean Difference in Tmax Between the Analog With Greatest and the Analog With the Least Value of Tmax for Individuals | 10, 20, 30, 40, 50, 60, 70, 80, 90, 100, 110, 120, 140, 160, 180, 200, 220, 240, 260, 280, 300 minutes after dose | The average difference in tmax between lispro and aspart in all participants |
| For Continuous Insulin Monitoring: Time to Maximum Plasma Insulin and Time to Maximum Continuous Insulin Monitoring Insulin | 10, 20, 30, 40, 50, 60, 70, 80, 90, 100, 110, 120, 140, 160, 180, 200, 220, 240, 260, 280, 300 minutes after dose | — |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Multiplex PK: Average Baseline HbA1c Categorized According to Baseline Use of Insulin Analog Found to Have the Most Favorable PK Profile for Each Individual | Baseline | Subjects with a difference in tmax between analogs will be categorized as follows: using insulin with best PK for them, using insulin with worst PK for them, or using insulin with intermediate PK for them. The average A1c for each of the three categories is reported. |
| Multiplex PK: Count of Subjects With Difference in Tmax Between the Analog With Greatest and the Analog With the Least Value of Tmax That is > 25% | 10, 20, 30, 40, 50, 60, 70, 80, 90, 100, 110, 120, 140, 160, 180, 200, 220, 240, 260, 280, 300 minutes after dose | — |
| Multiplex PK: Average Baseline HbA1c Categorized According to Baseline Use of Insulin Analog With Tmax < 60 Minutes vs. Use of an Insulin Analog With Tmax > 60 Minutes for Each Individual | Baseline | Subjects with a difference in tmax between analogs will be categorized as follows: using insulin with tmax less than or equal to 60 minutes or using insulin with tmax \> 60 minutes. The average A1c per group is reported. |
| Multiplex PK: Average Number of Hypoglycemia Events Over the Last Month at Baseline Categorized According to Baseline Use of Insulin Analog Found to Have the Most Favorable PK Profile for Each Individual | 1 month prior to study entry | Subjects with a difference in tmax between analogs will be categorized as follows: using insulin with best PK for them, using insulin with worst PK for them, or using insulin with intermediate PK for them. The average number of hypoglycemic events per month per group is reported. |
Countries
United States
Participant flow
Pre-assignment details
29 enrolled in Multiplex PK profiling, 9 were ineligible. 21 completed. 3 enrolled in the CIM arm of the trial. 2 completed, 1 was excluded from analysis. 1 subject enrolled in both study phases. They completed the MultiPK profiling experiments, but were excluded from the CIM analysis. Total protocol enrollment was 33.
Participants by arm
| Arm | Count |
|---|---|
| Multiplex Pharmacokinetic Profiling Multiplex pharmacokinetic profiling of regular human insulin, insulin aspart, insulin lispro, insulin glulisine, and regular human insulin
Multiplex pharmacokinetic profiling | 29 |
| Continuous Insulin Monitoring Continuous insulin monitoring of insulin lispro
Continuous insulin monitoring | 3 |
| Multiplex PK Profiling and Continuous Insulin Monitoring Participated in both study phases, the multiplex PK profiling visits and the CIM visits | 1 |
| Total | 33 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Excluded from Analysis | 1 | 1 | 1 |
| Overall Study | Inadequate Venous Access | 3 | 0 | 0 |
| Overall Study | Lost to Follow-up | 3 | 0 | 0 |
| Overall Study | Planning Pregnancy | 1 | 0 | 0 |
| Overall Study | Principal Investigator Determination | 1 | 0 | 0 |
Baseline characteristics
| Characteristic | Total | Multiplex Pharmacokinetic Profiling | Continuous Insulin Monitoring | Multiplex PK Profiling and Continuous Insulin Monitoring |
|---|---|---|---|---|
| Age, Continuous | 47.09 years STANDARD_DEVIATION 16.25 | 47.09 years STANDARD_DEVIATION 14.83 | 37.97 years STANDARD_DEVIATION 26.4 | 74.65 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 4 Participants | 3 Participants | 1 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 28 Participants | 25 Participants | 2 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants | 1 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 1 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 2 Participants | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 1 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 29 Participants | 26 Participants | 2 Participants | 1 Participants |
| Region of Enrollment United States | 25 participants | 29 participants | 3 participants | 1 participants |
| Sex: Female, Male Female | 19 Participants | 15 Participants | 3 Participants | 1 Participants |
| Sex: Female, Male Male | 14 Participants | 14 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 29 | 0 / 3 | 0 / 1 |
| other Total, other adverse events | 0 / 29 | 0 / 3 | 0 / 1 |
| serious Total, serious adverse events | 0 / 29 | 0 / 3 | 0 / 1 |
Outcome results
Primary
For Continuous Insulin Monitoring: Time to Maximum Plasma Insulin and Time to Maximum Continuous Insulin Monitoring Insulin
Time frame: 10, 20, 30, 40, 50, 60, 70, 80, 90, 100, 110, 120, 140, 160, 180, 200, 220, 240, 260, 280, 300 minutes after dose
Population: Only 2 of the 4 experiments conducted under the Continuous Insulin Monitoring sub-study protocol produced usable data for analysis. Those two experiments are both reported here
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| All Participants | For Continuous Insulin Monitoring: Time to Maximum Plasma Insulin and Time to Maximum Continuous Insulin Monitoring Insulin | Plasma insulin tmax | 40 minutes |
| All Participants | For Continuous Insulin Monitoring: Time to Maximum Plasma Insulin and Time to Maximum Continuous Insulin Monitoring Insulin | CIM insulin tmax | 44 minutes |
| Experiment #4 | For Continuous Insulin Monitoring: Time to Maximum Plasma Insulin and Time to Maximum Continuous Insulin Monitoring Insulin | Plasma insulin tmax | 60 minutes |
| Experiment #4 | For Continuous Insulin Monitoring: Time to Maximum Plasma Insulin and Time to Maximum Continuous Insulin Monitoring Insulin | CIM insulin tmax | 106 minutes |
Primary
For Multiplex PK Profiling: Aggregate Mean Difference in Tmax Between the Analog With Greatest and the Analog With the Least Value of Tmax for Individuals
The average difference in tmax between lispro and aspart in all participants
Time frame: 10, 20, 30, 40, 50, 60, 70, 80, 90, 100, 110, 120, 140, 160, 180, 200, 220, 240, 260, 280, 300 minutes after dose
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| All Participants | For Multiplex PK Profiling: Aggregate Mean Difference in Tmax Between the Analog With Greatest and the Analog With the Least Value of Tmax for Individuals | 24.28 minutes | Standard Deviation 41.29 |
Secondary
Multiplex PK: Average Baseline HbA1c Categorized According to Baseline Use of Insulin Analog Found to Have the Most Favorable PK Profile for Each Individual
Subjects with a difference in tmax between analogs will be categorized as follows: using insulin with best PK for them, using insulin with worst PK for them, or using insulin with intermediate PK for them. The average A1c for each of the three categories is reported.
Time frame: Baseline
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| All Participants | Multiplex PK: Average Baseline HbA1c Categorized According to Baseline Use of Insulin Analog Found to Have the Most Favorable PK Profile for Each Individual | 8.1 percentage of glycosylated hemoglobin | Standard Deviation 1.1 |
| Experiment #4 | Multiplex PK: Average Baseline HbA1c Categorized According to Baseline Use of Insulin Analog Found to Have the Most Favorable PK Profile for Each Individual | 8.6 percentage of glycosylated hemoglobin | Standard Deviation 1.8 |
| Participants Where the Two Insulins Were the Same | Multiplex PK: Average Baseline HbA1c Categorized According to Baseline Use of Insulin Analog Found to Have the Most Favorable PK Profile for Each Individual | 7.5 percentage of glycosylated hemoglobin | Standard Deviation 1.1 |
Secondary
Multiplex PK: Average Baseline HbA1c Categorized According to Baseline Use of Insulin Analog With Tmax < 60 Minutes vs. Use of an Insulin Analog With Tmax > 60 Minutes for Each Individual
Subjects with a difference in tmax between analogs will be categorized as follows: using insulin with tmax less than or equal to 60 minutes or using insulin with tmax \> 60 minutes. The average A1c per group is reported.
Time frame: Baseline
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| All Participants | Multiplex PK: Average Baseline HbA1c Categorized According to Baseline Use of Insulin Analog With Tmax < 60 Minutes vs. Use of an Insulin Analog With Tmax > 60 Minutes for Each Individual | 7.8 percentage of glycosylated hemoglobin | Standard Deviation 1.2 |
| Experiment #4 | Multiplex PK: Average Baseline HbA1c Categorized According to Baseline Use of Insulin Analog With Tmax < 60 Minutes vs. Use of an Insulin Analog With Tmax > 60 Minutes for Each Individual | 7.3 percentage of glycosylated hemoglobin | — |
Secondary
Multiplex PK: Average Number of Hypoglycemia Events Over the Last Month at Baseline Categorized According to Baseline Use of Insulin Analog Found to Have the Most Favorable PK Profile for Each Individual
Subjects with a difference in tmax between analogs will be categorized as follows: using insulin with best PK for them, using insulin with worst PK for them, or using insulin with intermediate PK for them. The average number of hypoglycemic events per month per group is reported.
Time frame: 1 month prior to study entry
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| All Participants | Multiplex PK: Average Number of Hypoglycemia Events Over the Last Month at Baseline Categorized According to Baseline Use of Insulin Analog Found to Have the Most Favorable PK Profile for Each Individual | 8.6 events in the month prior to study entry | Standard Deviation 12.1 |
| Experiment #4 | Multiplex PK: Average Number of Hypoglycemia Events Over the Last Month at Baseline Categorized According to Baseline Use of Insulin Analog Found to Have the Most Favorable PK Profile for Each Individual | 15.0 events in the month prior to study entry | Standard Deviation 15.6 |
| Participants Where the Two Insulins Were the Same | Multiplex PK: Average Number of Hypoglycemia Events Over the Last Month at Baseline Categorized According to Baseline Use of Insulin Analog Found to Have the Most Favorable PK Profile for Each Individual | 13.1 events in the month prior to study entry | Standard Deviation 13.9 |
Secondary
Multiplex PK: Count of Subjects With Difference in Tmax Between the Analog With Greatest and the Analog With the Least Value of Tmax That is > 25%
Time frame: 10, 20, 30, 40, 50, 60, 70, 80, 90, 100, 110, 120, 140, 160, 180, 200, 220, 240, 260, 280, 300 minutes after dose
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| All Participants | Multiplex PK: Count of Subjects With Difference in Tmax Between the Analog With Greatest and the Analog With the Least Value of Tmax That is > 25% | 11 Participants |