Diabetes Mellitus, Type 1
Conditions
Keywords
Insulin Degludec, Insulin Glargine, Air Travel, Continuous Glucose Monitor
Brief summary
The purpose of the proposed study is to compare insulin Degludec \[TRESIBA® (insulin degludec injection)\] with insulin Glargine U100 \[Lantus® (insulin glargine injection)\] to determine the basal insulin of choice for adults with type 1 diabetes (T1D) who fly non-stop across multiple time zones. With the introduction of Degludec as basal insulin for T1D and the opportunity to vary time of injection between 8 and 40 hours, the use of Degludec as a basal insulin may make it easier for both people living with T1D and diabetologists to plan long-haul travel compared to the use of existing basal insulins when crossing multiple time zones.The study hypothesis is that once daily Degludec as the basal insulin will provide better glycemic control for people with type 1 diabetes on multiple daily injections who are traveling non-stop across multiple time zones than once daily Glargine U100.
Detailed description
This study will be an open-label, single center, pilot study. Participants will be randomized to either Glargine U100 or Degludec as the basal insulin, then a 2 week break, and followed by a cross-over to the other insulin. Each study period will begin in Honolulu, Hawaii (HI) (airport code HNL) with a non-stop flight to Newark, New Jersey (NJ) (EWR) lasting approximately 10 hours with a 6 hour time difference between destinations. After up to 72 hours in EWR, participants will return to Honolulu and spend up to 72 hours at that destination. Investigators plan to recruit 25 adults with established T1D currently being treated with multiple daily injections of insulin (MDI).
Interventions
DRUGInsulin Degludec
Subjects will use Insulin Degludec (Tresiba) with TRESIBA® FLEXTOUCH® pens as their basal insulin during a 9-10 hour flight, at each destination, and then during a return flight.
DRUGInsulin Glargine
Subjects will use Insulin Glargine (Lantus) with LANTUS® SOLOSTAR® INSULIN PEN as their basal insulin during a 9-10 hour flight, at each destination, and then during a return flight.
DEVICETRESIBA® FLEXTOUCH®
Subjects will use Tresiba FlexTouch pens when using Tresiba as their basal insulin during a 9-10 hour flight, at each destination, and then during a return flight.
DEVICELANTUS® SOLOSTAR® INSULIN PEN
Subjects will use Lantus SoloStar insulin pens when using Lantus as their basal insulin during a 9-10 hour flight, at each destination, and then during a return flight.
Sponsors
Novo Nordisk A/S
Sansum Diabetes Research Institute
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Subjects will begin in Honolulu, HI (HNL), fly to Newark (EWR) where they will stay for up to 72 hours followed by a return long-haul flight back to Honolulu with up to 72 hours at this destination. This journey will be repeated after a 2 week period when subjects return to their original insulin treatment regimen and then switch to the alternative basal insulin.
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
1. Males or females ≥18 and ≤65 years of age. 2. Type 1 diabetes mellitus (diagnosed clinically and treated with multiple daily injections of insulin) for ≥12 months. 3. HbA1c \<10% within 30 days of being enrolled in the study 4. Current treatment with any basal insulin analogue as the once daily basal insulin given in the evening (22) and no fewer than three injections with rapid acting bolus insulin (e.g. insulin aspart, insulin lispro, or insulin glulisine) as mealtime bolus insulin therapy. 5. No contraindication to long-haul travel. 6. No recurrent severe hypoglycemia (more than 1 severe hypoglycemic event requiring hospitalization during the last 12 months), or hypoglycemia unawareness as judged by a score of \>4 on the Gold score (23), or hospitalization for diabetic ketoacidosis during the previous 6 months. 7. Willing and able to use a continuous glucose monitoring device (e.g. Dexcom G4). 8. Ability to self-manage insulin therapy (verbal confirmation at screening visit) of a changed bolus insulin dose the preceding 2 months prior to screening. 9. Ability and willingness to adhere to the protocol, including performance of self-monitored blood glucose (SMBG) readings and self-adjustment of insulin doses according to protocol. \-
Exclusion criteria
1. Current use of an insulin pump. 2. Use within the last 3 months prior to enrollment visit 1 of any glucose-lowering drug other than insulin. 3. Initiation or significant change of any systemic treatment which, in the investigator's opinion, could interfere with glucose metabolism, such as systemic corticosteroids, beta-blockers or monoamine oxidase inhibitors (inhaled corticosteroids allowed). 4. Proliferative retinopathy or maculopathy requiring treatment, according to the investigator. 5. Pregnancy, breast-feeding, the intention of becoming pregnant or not using adequate contraceptive measures. 6. Any clinically significant disease or disorder, which in the investigator's opinion could interfere with the results of the trial. 7. Mental incapacity, psychiatric disorder, unwillingness or language barriers precluding adequate understanding or cooperation, including subjects not able to read or write, and known or suspected abuse of alcohol, narcotics, or illicit drugs. 8. Known or suspected allergy to any of the trial products or related products. 9. Receipt of any investigational drug or participation in other trials within 1 month prior to Visit 1. \-
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Continuous Glucose Monitoring - Time in Range (70-140 mg/dl) | During the initial 24 hours local time and starting within 2 hours after arrival | Time in range (70-140 mg/dl) \[percentage of glucose readings or hours per day\] by continuous glucose monitoring (CGM) during the initial 24 hours local time (starting within 2 hours after arriving) in Newark, NJ after flying 9-10 hours West to East (from Honolulu, HI) and after the return journey from Newark to Honolulu (flying East to West). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Sleep Quantity Measured by ActiGraph | During 24 hours at each destination | Measurement of sleep duration (TST - Total sleep time in minutes) |
| Continuous Glucose Monitoring - Time in Range (70-180 mg/dl) | During the initial 24 hours local time and starting within 2 hours after arrival | Time in range (70-180 mg/dl) \[percentage of glucose readings or hours per day\] by continuous glucose monitoring (CGM) during the first 24 hours after arriving in HNL and EWR (starting within 2 hours after arrival). |
| Mean ± SD CGM Glucose (mg/dl) | In flight period of time and for 72 hours at each destination | Mean ± standard deviation of CGM glucose (mg/dl) by CGM during the flight and during the 72 hours at the destination |
| CGM % Time <70 mg/dl | In flight period of time and for 72 hours at each destination | % time \<70 mg/dl by CGM |
| Liverpool Jet-Lag Questionnaire | After 24 and 48 hours at the destination after arrival | This is a Questionnaire about jet-lag and fatigue administered at the destinations after arrival. Jet Lag is rated on a 0-10 scale (0 - insignificant jet lag to 10 - very bad jet lag). Fatigue is rated on a scale of -5 to +5 (more fatigue to less fatigue). |
| CGM % Time >180 mg/dl | In flight period of time and for 72 hours at each destination | % time \>180 mg/dl by CGM |
| CGM - Coefficient of Variation (CV) | In flight period of time and for 72 hours at each destination | Coefficient of variation of CGM values - glycemic variability (CV, %) |
| CGM Fasting Blood Glucose (FBG) | At 0600 local time on the morning after arrival at each destination | Fasting Blood Glucose (FBG) was determined using CGM at each destination on the morning after arrival. |
| Sleep Efficiency Measured by ActiGraph | During 24 hours at each destination | Measurement of sleep efficiency (SE% - total sleep time in minutes divided by time in bed in minutes) |
| CGM % Time 70-180 mg/dl | In flight period of time and for 72 hours at each destination | % time 70-180 mg/dl by CGM |
Countries
United States
Participant flow
Recruitment details
Between 2018-2019, 25 subjects from the local community were screened for eligibility and then randomly assigned to one arm of the study . When the first arm was completed, the subjects crossed over to the other arm of the study.
Pre-assignment details
25 Participants were randomly assigned to one arm and then crossed over to the other arm when the first assignment was completed.
Participants by arm
| Arm | Count |
|---|---|
| All Study Participants Subjects with type 1 diabetes and on multiple daily injections will use either basal insulin Glargine U100 and the LANTUS® SOLOSTAR® INSULIN PEN or they will use basal insulin Degludec and the TRESIBA® FLEXTOUCH® pens during a long-haul flight and randomized to these arms first or second.
For Insulin Glargine: Subjects will use Insulin Glargine (Lantus) with LANTUS® SOLOSTAR® INSULIN PEN as their basal insulin during a 9-10 hour flight, at each destination, and then during a return flight. After a washout period of 2 weeks, subjects crossed over to the other basal insulin, Insulin Degludec.
For Insulin Degludec: Subjects will use Insulin Degludec (Tresiba) with TRESIBA® FLEXTOUCH® pens as their basal insulin during a 9-10 hour flight, at each destination, and then during a return flight. After a washout period of 2 weeks, the subjects crossed over to the other basal insulin, Insulin Glargine. | 25 |
| Total | 25 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| First Intervention | Withdrawal by Subject | 2 | 2 |
Baseline characteristics
| Characteristic | All Study Participants |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 25 Participants |
| Age, Continuous | 35 years STANDARD_DEVIATION 14.5 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 3 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 22 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Hypoglycemia awareness Fear of hypoglycemia scale | 36.6 units on a scale STANDARD_DEVIATION 18.1 |
| Hypoglycemia awareness Gold score | 2.0 units on a scale STANDARD_DEVIATION 1.2 |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants |
| Race (NIH/OMB) Asian | 1 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 23 Participants |
| Region of Enrollment United States | 25 participants |
| Sex: Female, Male Female | 14 Participants |
| Sex: Female, Male Male | 11 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 21 | 0 / 21 |
| other Total, other adverse events | 0 / 21 | 0 / 21 |
| serious Total, serious adverse events | 0 / 21 | 0 / 21 |
Outcome results
Primary
Continuous Glucose Monitoring - Time in Range (70-140 mg/dl)
Time in range (70-140 mg/dl) \[percentage of glucose readings or hours per day\] by continuous glucose monitoring (CGM) during the initial 24 hours local time (starting within 2 hours after arriving) in Newark, NJ after flying 9-10 hours West to East (from Honolulu, HI) and after the return journey from Newark to Honolulu (flying East to West).
Time frame: During the initial 24 hours local time and starting within 2 hours after arrival
Population: All participants (n=21) who completed both arms of the study were included in the analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Insulin Degludec | Continuous Glucose Monitoring - Time in Range (70-140 mg/dl) | Eastward travel | 36.3 percentage of Time in Range 70-140mg/dL | Standard Deviation 22.2 |
| Insulin Degludec | Continuous Glucose Monitoring - Time in Range (70-140 mg/dl) | Westward travel | 37.2 percentage of Time in Range 70-140mg/dL | Standard Deviation 22.2 |
| Insulin Glargine U100 | Continuous Glucose Monitoring - Time in Range (70-140 mg/dl) | Eastward travel | 45.6 percentage of Time in Range 70-140mg/dL | Standard Deviation 21.1 |
| Insulin Glargine U100 | Continuous Glucose Monitoring - Time in Range (70-140 mg/dl) | Westward travel | 43.9 percentage of Time in Range 70-140mg/dL | Standard Deviation 20 |
Comparison: Null hypothesis is there was no difference in Time in Range (70-140mg/dl) in the initial 24 hours at destination, whether after Eastward travel or Westward travel, between Insulin Degludec \& Insulin Glargine U100. Travel direction not tested. Criterion for significance set at 0.05; using paired t-test analysis, a sample size of 21 subjects would achieve a power of at least 77% to detect a difference of 10% between basal insulins assuming the standard deviation of the difference is \<106 minutes.p-value: <0.05t-test, 2 sided
Secondary
CGM - Coefficient of Variation (CV)
Coefficient of variation of CGM values - glycemic variability (CV, %)
Time frame: In flight period of time and for 72 hours at each destination
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Insulin Degludec | CGM - Coefficient of Variation (CV) | Eastward In-flight Glycemic variability CV % | 30.6 percentage of Glycemic Variability % | Standard Deviation 15.9 |
| Insulin Degludec | CGM - Coefficient of Variation (CV) | Eastward 72-hours at destination Glycemic variability CV % | 39.9 percentage of Glycemic Variability % | Standard Deviation 9.3 |
| Insulin Degludec | CGM - Coefficient of Variation (CV) | Westward In-flight Glycemic variability CV % | 28.2 percentage of Glycemic Variability % | Standard Deviation 8.4 |
| Insulin Degludec | CGM - Coefficient of Variation (CV) | Westward 72-hours at destination Glycemic variability CV % | 38.6 percentage of Glycemic Variability % | Standard Deviation 7.4 |
| Insulin Glargine U100 | CGM - Coefficient of Variation (CV) | Westward In-flight Glycemic variability CV % | 33.7 percentage of Glycemic Variability % | Standard Deviation 10.1 |
| Insulin Glargine U100 | CGM - Coefficient of Variation (CV) | Eastward In-flight Glycemic variability CV % | 31.0 percentage of Glycemic Variability % | Standard Deviation 14 |
| Insulin Glargine U100 | CGM - Coefficient of Variation (CV) | Westward 72-hours at destination Glycemic variability CV % | 39.5 percentage of Glycemic Variability % | Standard Deviation 9.3 |
| Insulin Glargine U100 | CGM - Coefficient of Variation (CV) | Eastward 72-hours at destination Glycemic variability CV % | 41.0 percentage of Glycemic Variability % | Standard Deviation 10.8 |
Comparison: Null hypothesis is there was no difference in CGM - Coefficient of Variation (CV) in flight, East or West travel, and in 72 hours at destination, whether after East or West travel, between Insulin Degludec \& Insulin Glargine U100. Travel direction not tested. Criterion for significance was at 0.05. Using paired t-test analysis, a sample size of 21 subjects would achieve a power of at least 77% to detect a difference of 10% between basal insulins assuming the SD of the difference is \<106 minutes.p-value: <0.05t-test, 2 sided
Secondary
CGM Fasting Blood Glucose (FBG)
Fasting Blood Glucose (FBG) was determined using CGM at each destination on the morning after arrival.
Time frame: At 0600 local time on the morning after arrival at each destination
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Insulin Degludec | CGM Fasting Blood Glucose (FBG) | After eastward travel | 143 mg/dL | Standard Deviation 80 |
| Insulin Degludec | CGM Fasting Blood Glucose (FBG) | After westward travel | 137 mg/dL | Standard Deviation 60 |
| Insulin Glargine U100 | CGM Fasting Blood Glucose (FBG) | After eastward travel | 137 mg/dL | Standard Deviation 60 |
| Insulin Glargine U100 | CGM Fasting Blood Glucose (FBG) | After westward travel | 140 mg/dL | Standard Deviation 79 |
Comparison: Null hypothesis is there was no difference in CGM Fasting Blood Glucose (FBG) at 0600 local time at destination, whether after East or West travel, between Insulin Degludec and Insulin Glargine U100. Travel direction not tested. Criterion for significance was set at 0.05, and using a paired t-test analysis, a sample size of 21 subjects would achieve a power of at least 77% to detect a difference of 10% between basal insulins assuming the standard deviation of the difference is \<106 minutes.p-value: <0.05t-test, 2 sided
Secondary
CGM % Time >180 mg/dl
% time \>180 mg/dl by CGM
Time frame: In flight period of time and for 72 hours at each destination
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Insulin Degludec | CGM % Time >180 mg/dl | In flight Eastward travel %Time above Range >180mg/dL | 39.5 percentage of Time above Range >180mg/dL | Standard Deviation 27.9 |
| Insulin Degludec | CGM % Time >180 mg/dl | In flight Westward travel %Time above Range >180mg/dL | 30.8 percentage of Time above Range >180mg/dL | Standard Deviation 25.4 |
| Insulin Degludec | CGM % Time >180 mg/dl | Eastward 72 hours at destination % Time above Range >180mg/dL | 31.7 percentage of Time above Range >180mg/dL | Standard Deviation 21.3 |
| Insulin Degludec | CGM % Time >180 mg/dl | Westward 72 hours at destination % Time above Range >180mg/dL | 34.9 percentage of Time above Range >180mg/dL | Standard Deviation 21.9 |
| Insulin Glargine U100 | CGM % Time >180 mg/dl | Westward 72 hours at destination % Time above Range >180mg/dL | 32.7 percentage of Time above Range >180mg/dL | Standard Deviation 23.1 |
| Insulin Glargine U100 | CGM % Time >180 mg/dl | In flight Eastward travel %Time above Range >180mg/dL | 32.3 percentage of Time above Range >180mg/dL | Standard Deviation 31.5 |
| Insulin Glargine U100 | CGM % Time >180 mg/dl | Eastward 72 hours at destination % Time above Range >180mg/dL | 27.6 percentage of Time above Range >180mg/dL | Standard Deviation 17.2 |
| Insulin Glargine U100 | CGM % Time >180 mg/dl | In flight Westward travel %Time above Range >180mg/dL | 26.0 percentage of Time above Range >180mg/dL | Standard Deviation 23.5 |
Comparison: Null hypothesis is that there was no difference in CGM % time \>180 mg/dl in flight, East or West travel, and in 72 hours at destination, whether after East or West travel, between Insulin Degludec \& Insulin Glargine U100. Travel direction not tested. Criterion for significance was at 0.05. Using paired t-test analysis, a sample size of 21 subjects would achieve a power of at least 77% to detect a difference of 10% between basal insulins assuming the SD of the difference is \<106 minutes.p-value: <0.05t-test, 2 sided
Secondary
CGM % Time 70-180 mg/dl
% time 70-180 mg/dl by CGM
Time frame: In flight period of time and for 72 hours at each destination
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Insulin Degludec | CGM % Time 70-180 mg/dl | Eastward travel in-flight | 50.5 percentage of Time in Range 70-180mg/dL | Standard Deviation 24 |
| Insulin Degludec | CGM % Time 70-180 mg/dl | Westward travel in-flight | 65.1 percentage of Time in Range 70-180mg/dL | Standard Deviation 23.6 |
| Insulin Degludec | CGM % Time 70-180 mg/dl | Eastward travel 72 hours at destination | 58.3 percentage of Time in Range 70-180mg/dL | Standard Deviation 18.8 |
| Insulin Degludec | CGM % Time 70-180 mg/dl | Westward travel 72 hours at destination | 56.7 percentage of Time in Range 70-180mg/dL | Standard Deviation 18.8 |
| Insulin Glargine U100 | CGM % Time 70-180 mg/dl | Westward travel 72 hours at destination | 59.2 percentage of Time in Range 70-180mg/dL | Standard Deviation 23 |
| Insulin Glargine U100 | CGM % Time 70-180 mg/dl | Eastward travel in-flight | 58.9 percentage of Time in Range 70-180mg/dL | Standard Deviation 30.8 |
| Insulin Glargine U100 | CGM % Time 70-180 mg/dl | Eastward travel 72 hours at destination | 62.0 percentage of Time in Range 70-180mg/dL | Standard Deviation 16.2 |
| Insulin Glargine U100 | CGM % Time 70-180 mg/dl | Westward travel in-flight | 64.0 percentage of Time in Range 70-180mg/dL | Standard Deviation 21 |
Comparison: Null hypothesis is that there was no difference in CGM % time 70-180 mg/dl in flight, East or West travel, and in 72 hours at destination, whether after East or West travel, between Insulin Degludec \& Insulin Glargine U100. Travel direction not tested. Criterion for significance was at 0.05. Using paired t-test analysis, a sample size of 21 subjects would achieve a power of at least 77% to detect a difference of 10% between basal insulins assuming the SD of the difference is \<106 minutes.p-value: <0.05t-test, 2 sided
Secondary
CGM % Time <70 mg/dl
% time \<70 mg/dl by CGM
Time frame: In flight period of time and for 72 hours at each destination
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Insulin Degludec | CGM % Time <70 mg/dl | Eastward travel in flight | 9.9 percentage of Time below range <70 mg/dL | Standard Deviation 21.5 |
| Insulin Degludec | CGM % Time <70 mg/dl | Eastward flight 72 hours at destination | 10.0 percentage of Time below range <70 mg/dL | Standard Deviation 9.6 |
| Insulin Degludec | CGM % Time <70 mg/dl | Westward travel in flight | 4.1 percentage of Time below range <70 mg/dL | Standard Deviation 7.3 |
| Insulin Degludec | CGM % Time <70 mg/dl | Westward flight 72 hours at destination | 8.4 percentage of Time below range <70 mg/dL | Standard Deviation 6.8 |
| Insulin Glargine U100 | CGM % Time <70 mg/dl | Westward travel in flight | 9.9 percentage of Time below range <70 mg/dL | Standard Deviation 12.9 |
| Insulin Glargine U100 | CGM % Time <70 mg/dl | Eastward travel in flight | 8.9 percentage of Time below range <70 mg/dL | Standard Deviation 13.5 |
| Insulin Glargine U100 | CGM % Time <70 mg/dl | Westward flight 72 hours at destination | 8.2 percentage of Time below range <70 mg/dL | Standard Deviation 6.9 |
| Insulin Glargine U100 | CGM % Time <70 mg/dl | Eastward flight 72 hours at destination | 10.5 percentage of Time below range <70 mg/dL | Standard Deviation 8.6 |
Comparison: Null hypothesis is that there was no difference in CGM % time \<70 mg/dl in flight, East or West travel, and in 72 hours at destination, whether after East or West travel, between Insulin Degludec and Insulin Glargine U100. Travel direction not tested. Criterion for significance was at 0.05. Using paired t-test analysis, a sample size of 21 subjects would achieve a power of at least 77% to detect a difference of 10% between basal insulins assuming the SD of the difference is \<106 minutes.p-value: <0.05t-test, 2 sided
Secondary
Continuous Glucose Monitoring - Time in Range (70-180 mg/dl)
Time in range (70-180 mg/dl) \[percentage of glucose readings or hours per day\] by continuous glucose monitoring (CGM) during the first 24 hours after arriving in HNL and EWR (starting within 2 hours after arrival).
Time frame: During the initial 24 hours local time and starting within 2 hours after arrival
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Insulin Degludec | Continuous Glucose Monitoring - Time in Range (70-180 mg/dl) | Eastward travel | 55.0 percentage of Time in Range 70-180mg/dL | Standard Deviation 21.7 |
| Insulin Degludec | Continuous Glucose Monitoring - Time in Range (70-180 mg/dl) | Westward travel | 54.5 percentage of Time in Range 70-180mg/dL | Standard Deviation 24.7 |
| Insulin Glargine U100 | Continuous Glucose Monitoring - Time in Range (70-180 mg/dl) | Eastward travel | 62.3 percentage of Time in Range 70-180mg/dL | Standard Deviation 19.3 |
| Insulin Glargine U100 | Continuous Glucose Monitoring - Time in Range (70-180 mg/dl) | Westward travel | 61.2 percentage of Time in Range 70-180mg/dL | Standard Deviation 24.7 |
Comparison: Null hypothesis is there was no difference in Time in Range (70-180mg/dl) in the initial 24 hours at destination, whether after Eastward travel or Westward travel, between Insulin Degludec \& Insulin Glargine U100. Travel direction not tested. Criterion for significance set at 0.05; using paired t-test analysis, a sample size of 21 subjects would achieve a power of at least 77% to detect a difference of 10% between basal insulins assuming the standard deviation of the difference is \<106 minutes.p-value: <0.05t-test, 2 sided
Secondary
Liverpool Jet-Lag Questionnaire
This is a Questionnaire about jet-lag and fatigue administered at the destinations after arrival. Jet Lag is rated on a 0-10 scale (0 - insignificant jet lag to 10 - very bad jet lag). Fatigue is rated on a scale of -5 to +5 (more fatigue to less fatigue).
Time frame: After 24 and 48 hours at the destination after arrival
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Insulin Degludec | Liverpool Jet-Lag Questionnaire | Eastward jet lag after 24 hours | 2.5 score on a scale | Standard Deviation 2.6 |
| Insulin Degludec | Liverpool Jet-Lag Questionnaire | Westward jetlag after 24 hours | 3.2 score on a scale | Standard Deviation 3.3 |
| Insulin Degludec | Liverpool Jet-Lag Questionnaire | Eastward fatigue after 24 hours | 0.2 score on a scale | Standard Deviation 1.6 |
| Insulin Degludec | Liverpool Jet-Lag Questionnaire | Eastward jet lag after 48 hours | 1.6 score on a scale | Standard Deviation 2.7 |
| Insulin Degludec | Liverpool Jet-Lag Questionnaire | Westward fatigue after 24 hours | -1.6 score on a scale | Standard Deviation 2 |
| Insulin Degludec | Liverpool Jet-Lag Questionnaire | Eastward fatigue after 48 hours | -0.7 score on a scale | Standard Deviation 1.8 |
| Insulin Degludec | Liverpool Jet-Lag Questionnaire | Westward fatigue after 48 hours | 3.5 score on a scale | Standard Deviation 2.9 |
| Insulin Degludec | Liverpool Jet-Lag Questionnaire | Westward jetlag after 48 hours | 3.5 score on a scale | Standard Deviation 2.9 |
| Insulin Glargine U100 | Liverpool Jet-Lag Questionnaire | Westward fatigue after 48 hours | -0.7 score on a scale | Standard Deviation 2.4 |
| Insulin Glargine U100 | Liverpool Jet-Lag Questionnaire | Eastward jet lag after 24 hours | 4.1 score on a scale | Standard Deviation 2.8 |
| Insulin Glargine U100 | Liverpool Jet-Lag Questionnaire | Eastward jet lag after 48 hours | 3.8 score on a scale | Standard Deviation 3.4 |
| Insulin Glargine U100 | Liverpool Jet-Lag Questionnaire | Eastward fatigue after 24 hours | 0.2 score on a scale | Standard Deviation 2.7 |
| Insulin Glargine U100 | Liverpool Jet-Lag Questionnaire | Eastward fatigue after 48 hours | -1.5 score on a scale | Standard Deviation 2.3 |
| Insulin Glargine U100 | Liverpool Jet-Lag Questionnaire | Westward jetlag after 24 hours | 3.5 score on a scale | Standard Deviation 3.3 |
| Insulin Glargine U100 | Liverpool Jet-Lag Questionnaire | Westward jetlag after 48 hours | 2.9 score on a scale | Standard Deviation 3.3 |
| Insulin Glargine U100 | Liverpool Jet-Lag Questionnaire | Westward fatigue after 24 hours | -1.5 score on a scale | Standard Deviation 2.3 |
Comparison: Null hypothesis is that there was no difference in Liverpool Jet-Lag Questionnaire after 24 and 48 hours at the destination, whether after Eastward travel or after Westward travel, between Insulin Degludec and Insulin Glargine U100. Travel direction not tested. The criterion for significance was set at 0.05, and using a paired t-test analysis, a sample size of 21 subjects would achieve a power of at least 77% to detect a difference of 10% between basal insulins.p-value: <0.01t-test, 2 sided
Secondary
Mean ± SD CGM Glucose (mg/dl)
Mean ± standard deviation of CGM glucose (mg/dl) by CGM during the flight and during the 72 hours at the destination
Time frame: In flight period of time and for 72 hours at each destination
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Insulin Degludec | Mean ± SD CGM Glucose (mg/dl) | In-flight eastward | 166.3 mg/dL | Standard Deviation 55.2 |
| Insulin Degludec | Mean ± SD CGM Glucose (mg/dl) | In-flight westward | 157.0 mg/dL | Standard Deviation 37.5 |
| Insulin Degludec | Mean ± SD CGM Glucose (mg/dl) | 72 hours at destination after eastward travel | 154.3 mg/dL | Standard Deviation 43.8 |
| Insulin Degludec | Mean ± SD CGM Glucose (mg/dl) | 72 hours at destination after westward travel | 160.4 mg/dL | Standard Deviation 35.4 |
| Insulin Glargine U100 | Mean ± SD CGM Glucose (mg/dl) | 72 hours at destination after westward travel | 156.3 mg/dL | Standard Deviation 34.6 |
| Insulin Glargine U100 | Mean ± SD CGM Glucose (mg/dl) | In-flight eastward | 158.8 mg/dL | Standard Deviation 58.9 |
| Insulin Glargine U100 | Mean ± SD CGM Glucose (mg/dl) | 72 hours at destination after eastward travel | 147.6 mg/dL | Standard Deviation 34 |
| Insulin Glargine U100 | Mean ± SD CGM Glucose (mg/dl) | In-flight westward | 146.1 mg/dL | Standard Deviation 52.3 |
Comparison: Null hypothesis is there was no difference in Mean ± SD CGM glucose (mg/dl) in flight, East or West travel, and in 72 hours at destination, whether after East or West travel, between Insulin Degludec \& Insulin Glargine U100. Travel direction not tested. Criterion for significance was at 0.05. Using paired t-test analysis, a sample size of 21 subjects would achieve a power of at least 77% to detect a difference of 10% between basal insulins assuming the SD of the difference is \<106 minutes.p-value: <0.05t-test, 2 sided
Secondary
Sleep Efficiency Measured by ActiGraph
Measurement of sleep efficiency (SE% - total sleep time in minutes divided by time in bed in minutes)
Time frame: During 24 hours at each destination
Population: The pre-specified intent was to combine insulin arms if there were no differences between insulin arms. Sleep quality/efficiency was compared at each destination.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Insulin Degludec | Sleep Efficiency Measured by ActiGraph | SE% in NY | 92 percentage of total sleep/time in bed |
| Insulin Degludec | Sleep Efficiency Measured by ActiGraph | SE% in HI | 89 percentage of total sleep/time in bed |
Comparison: Null hypothesis is there was no difference in Sleep efficiency measured by ActiGraph in 24 hours at the destination, whether after Eastward or after Westward travel, between Insulin Degludec and Insulin Glargine U100. Travel direction not tested. The criterion for significance was set at 0.05, and using a paired t-test analysis, a sample size of 21 subjects would achieve a power of at least 77% to detect a difference of 10% between basal insulins.p-value: <0.05Wilcoxon (Mann-Whitney)
Secondary
Sleep Quantity Measured by ActiGraph
Measurement of sleep duration (TST - Total sleep time in minutes)
Time frame: During 24 hours at each destination
Population: The pre-specified intent was to combine insulin arms if there were no differences between insulin arms. Sleep quantity was compared at each destination.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Insulin Degludec | Sleep Quantity Measured by ActiGraph | Total sleep time, minutes in NY | 489 Minutes |
| Insulin Degludec | Sleep Quantity Measured by ActiGraph | Total sleep time, minutes in HI | 398 Minutes |
Comparison: Null hypothesis is that there was no difference in Sleep quantity measured by ActiGraph in 24 hours at the destination, whether after Eastward or after Westward travel, between Insulin Degludec and Insulin Glargine U100. Travel direction not tested. The criterion for significance was set at 0.05, and using a paired t-test analysis, a sample size of 21 subjects would achieve a power of at least 77% to detect a difference of 10% between basal insulins.p-value: <0.05Wilcoxon (Mann-Whitney)