Comparison of Insulin Degludec With Insulin Glargine U100 for Adults With Type 1 Diabetes Crossing Multiple Time Zones.

Study Overview
=================
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).

Official Title
-----------------
Comparison of Insulin Degludec With Insulin Glargine U100 for Adults With Type 1 Diabetes Travelling Across Multiple Time Zones. A Pilot Study.

Conditions
-----------------
Diabetes Mellitus, Type 1

Intervention / Treatment
-----------------
* Drug: Insulin Degludec
* Drug: Insulin Glargine
* Device: TRESIBA® FLEXTOUCH®
* Device: LANTUS® SOLOSTAR® INSULIN PEN


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Males or females ≥18 and ≤65 years of age. Type 1 diabetes mellitus (diagnosed clinically and treated with multiple daily injections of insulin) for ≥12 months. HbA1c <10% within 30 days of being enrolled in the study 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. No contraindication to long-haul travel. 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. Willing and able to use a continuous glucose monitoring device (e.g. Dexcom G4). Ability to self-manage insulin therapy (verbal confirmation at screening visit) of a changed bolus insulin dose the preceding 2 months prior to screening. 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: Current use of an insulin pump. Use within the last 3 months prior to enrollment visit 1 of any glucose-lowering drug other than insulin. 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). Proliferative retinopathy or maculopathy requiring treatment, according to the investigator. Pregnancy, breast-feeding, the intention of becoming pregnant or not using adequate contraceptive measures. Any clinically significant disease or disorder, which in the investigator's opinion could interfere with the results of the trial. 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. Known or suspected allergy to any of the trial products or related products. Receipt of any investigational drug or participation in other trials within 1 month prior to Visit 1. -

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional 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.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Insulin Degludec<br>Subjects with type 1 diabetes and on multiple daily injections will use basal insulin Degludec and the TRESIBA® FLEXTOUCH® pens during a long-haul flight and randomized to this arm first or second. | Drug: Insulin Degludec<br>* 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.<br>* Other names: Tresiba;Device: TRESIBA® FLEXTOUCH®<br>* 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.<br>* Other names: Insulin Degludec;|
| Active Comparator: Insulin Glargine U100<br>Subjects with type 1 diabetes and on multiple daily injections will use basal insulin Glargine U100 and the LANTUS® SOLOSTAR® INSULIN PEN during a long-haul flight and randomized to this arm first or second. | Drug: Insulin Glargine<br>* 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.<br>* Other names: Lantus;Device: LANTUS® SOLOSTAR® INSULIN PEN<br>* 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.<br>* Other names: Insulin Glargine;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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). | During the initial 24 hours local time and starting within 2 hours after arrival | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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). | During the initial 24 hours local time and starting within 2 hours after arrival | 
| 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 | In flight period of time and for 72 hours at each destination | 
| CGM % Time <70 mg/dl | % time <70 mg/dl by CGM | In flight period of time and for 72 hours at each destination | 
| CGM % Time 70-180 mg/dl | % time 70-180 mg/dl by CGM | In flight period of time and for 72 hours at each destination | 
| CGM % Time >180 mg/dl | % time >180 mg/dl by CGM | In flight period of time and for 72 hours at each destination | 
| CGM - Coefficient of Variation (CV) | Coefficient of variation of CGM values - glycemic variability (CV, %) | In flight period of time and for 72 hours at each destination | 
| CGM Fasting Blood Glucose (FBG) | Fasting Blood Glucose (FBG) was determined using CGM at each destination on the morning after arrival. | At 0600 local time on the morning after arrival at each destination | 
| 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). | After 24 and 48 hours at the destination after arrival | 
| Sleep Quantity Measured by ActiGraph | Measurement of sleep duration (TST - Total sleep time in minutes) | During 24 hours at each destination | 
| Sleep Efficiency Measured by ActiGraph | Measurement of sleep efficiency (SE% - total sleep time in minutes divided by time in bed in minutes) | During 24 hours at each destination | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Insulin Degludec, Insulin Glargine, Air Travel, Continuous Glucose Monitor