Flexible Insulin Therapy Untethered Insulin Regimen in Avidly Exercising Patients With Type 1 Diabetes: FIT Untethered

Study Overview
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Brief Summary
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The overall objective of this study is to evaluate glycemic control and patient-reported outcomes in patients with Type 1 diabetes (T1D) who use insulin degludec and continuous subcutaneous insulin infusion in a combination untethered regimen during moderate or high-intensity exercise.

Detailed Description
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FIT untethered is an open-label, randomized, repeated measures cross-over design study, testing glycemic control in untethered continuous subcutaneous insulin infusion (CSII) therapy compared to usual CSII therapy, in physically active patients with T1D (N=30). During 2-week screening visits, participants are randomized into either the usual CSII arm or the untethered CSII arm. Patients in the usual group continue with their established CSII therapy. Patients in the untethered group are to administer 50% of their basal dose through an insulin degludec injection every morning, with the other 50% achieved through their established CSII therapy. Bolus insulin remains at the established dose in both groups. After randomization, patients begin Phase I and transition into a 2-week insulin optimization period. Then, participants will complete 2 in-clinic, supervised exercise visits (1 moderate and 1 high intensity exercises) in the following week. After, participants must complete 2 unsupervised at-home exercises per week for 3 weeks (cumulative total of 2 moderate and 4 high intensity exercises). After the home exercise period, participants cross-over to the other study arm and begin Phase II. Phase II is similar to Phase I: 2 weeks of insulin dose optimization, 1 week of supervised clinic exercise, and 3 weeks of unsupervised home exercise. For both in-clinic and home-based exercise, the participant's insulin pump will be disconnected and suspended 60 minutes prior to beginning the workout, and will be reconnected immediately following each workout. A continuous glucose monitoring (CGM) device will be worn by each participant for the entire duration of the study. The co-primary outcomes of the study include time in range (4.0 - 10.0 mmol/L) in the 6 hours after the start of moderate- and high-intensity exercise. The key secondary outcomes include the glucose variability during the 24 hour period after the start of both moderate and high intensity exercise, and patient reported outcomes before and after exercise.

Official Title
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Flexible Insulin Therapy Untethered Insulin Regimen Using Insulin Degludec and Continuous Subcutaneous Insulin Infusion in Avidly Exercising Patients With Type 1 Diabetes: FIT Untethered

Conditions
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Type 1 Diabetes Mellitus

Intervention / Treatment
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* Drug: Insulin Degludec


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adults with clinical diagnosis of T1D Age 18-55 years, inclusive Diagnosis of T1D ≥ 6 months A1c ≤ 8.5% at screening visit Using stable CSII therapy for ≥ 6 months Exercise regularly (≥ 3 times per week of moderate or vigorous exercise) VO2peak ≥ 30 ml/kg/min for females and ≥ 32 ml/kg/min for males Willing to adhere to the protocol requirements for the duration of the study Written informed consent Fasting C-peptide value of < 0.7 ng/mL (0.23 nmol/L) at screening visit Exclusion Criteria: Pregnant or lactating Already using a split regimen of combination CSII and basal insulin injection Active diabetic retinopathy (proliferated diabetic retinopathy, or vitreous hemorrhage in past 6 months) that could potentially be worsened by the exercise protocol Any evidence of unstable cardiovascular disease, disorders or abnormalities as per physician's discretion Currently following a very low calorie or other weight-loss diet which may impact glucose control and mask the primary and secondary outcome measures More than one episode of severe hypoglycemia with seizure, coma or requiring assistance of another person during the past 6 months Known hypoglycemia unawareness Use of acetaminophen (Tylenol) during the study period Medications other than insulin that might impact outcome measures: Beta blockers Any agents that affect hepatic glucose production, including all beta adrenergic agonists or antagonists, all xanthine derivatives Pramlintide Any non-insulin diabetes therapy

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: Randomization for the sequence of Interventions (A and B) will be done by an interactive system that will randomly assign patients to an intervention sequence.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: Usual CSII<br>Continue to use the established CSII insulin therapy | |
| Experimental: Untethered CSII<br>Basal dosing - total CSII basal dose will be delivered by 50% through continuing CSII therapy used prior to study enrollment and 50% through the addition of once daily insulin degludec injected in the morning; Bolus dosing - continue the established bolus insulin dose | Drug: Insulin Degludec<br>* 50% of the patient's daily basal insulin dose delivered through once daily insulin degludec injected in the morning; 50% of the basal insulin to be delivered through previously established CSII<br>* Other names: Tresiba;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time in range within 6 hours | Percentage of time with CGM glucose between 4.0 - 10.0 mmol/L within 6 hours after the start of high-intensity or moderate-intensity, in-clinic exercise | 6 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in glucose within 60 mins after high-intensity exercise starts | Plasma glucose at 30 mins after after the end of a 30-min high-intensity, in-clinic exercise minus plasma glucose at baseline (right before exercise) | 60 mins | 
| Change in glucose within 120 mins after moderate-intensity exercise starts | Plasma glucose at 30 mins after the end of a 90-min moderate-intensity, in-clinic exercise minus plasma glucose at baseline (right before exercise) | 120 mins | 
| Time spent in hypoglycemia 24 hours after exercise | Percentage of time with CGM glucose <4.0 mmol/L within 24 hour after the start of high intensity exercise or moderate intensity in-clinic exercise | 24 hours | 
| Time in range 24 hours after exercise | Percentage of time with CGM glucose between 4.0 - 10.0 mmol/L within 24 hour after the start of high intensity exercise or moderate intensity in-clinic exercise | 24 hours | 
| Time spent in hyperglycemia 24 hours after exercise | Percentage of time with CGM glucose > 10.0 mmol/L within 24 hour after the start of high intensity exercise or moderate intensity in-clinic exercise | 24 hours | 
| Time in range in the last 4 weeks of each study phase | Percentage of time with CGM glucose between 4.0 - 10.0 mmol/L in the last 4 weeks of each study phase | 4 weeks | 
| Frequency of hypoglycemia 24 hours after exercise | Number of hypoglycemic episodes, which are defined as CGM glucose <4.0 mmol/L lasting ≥15 minutes within 24 hours following high intensity exercise or moderate intensity in-clinic exercise | 24 hours | 
| Frequency of hypoglycemia in the last 4 weeks of each study phase | Number of hypoglycemic episodes, which are defined as CGM glucose <4.0 mmol/L lasting ≥15 minutes in the last 4 weeks of each study phase | 4 weeks | 
| Change in Diabetes Medication Satisfaction (DiabMedSat) Score | Diabetes Medication Satisfaction questionnaire is to measure the level of patients' satisfaction with their diabetes medication(s) in the past 2 weeks. The score range will be 0 to 100. The higher the score, the less the satisfaction. The change of scores is the score difference between Visit 24 and Visit 2 | 11 weeks | 
| Change in Hypoglycemia Fear Score | Hypoglycemia Fear will be measured by the Hypoglycemia Fear Survey which assesses the subject's behaviors to avoid hypoglycemia and to measure the subjects' worries about hypoglycemia and its consequences in the past 3 months. The range of the score will be 0 to 132. The higher the score, the greater the fear. The changes of scores are the score difference between Visit 24 and Visit 2 | 11 weeks | 
| Change in TRIM-D Score | Treatment Related Impact Measure - Diabetes Device (TRIM-D Device) questionnaire will be used to generate TRIM-D-Score. It measures the level of the subject's satisfaction with the device used to take the diabetes medication. The range of this score will be 3-15. The higher the score, The greater satisfaction. The changes of scores are the score difference between Visit 24 and Visit 2 | 11 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Exercise, Insulin Degludec, Continuous glucose monitoring (CGM), Continuous Subcutaneous Insulin Infusion (CSII)