Clinical trial NCT03838783: Flexible Insulin Therapy Untethered Insulin Regimen in Avidly Exercising Patients With Type 1 Diabetes: FIT Untethered
Official title: Flexible Insulin Therapy Untethered Insulin Regimen Using Insulin Degludec and Continuous Subcutaneous Insulin Infusion in Avidly Exercising Patients With Type 1 Diabetes: FIT Untethered
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: Type 1 Diabetes Mellitus
Keywords: Exercise
Insulin Degludec
Continuous glucose monitoring (CGM)
Continuous Subcutaneous Insulin Infusion (CSII)
Lead sponsor: LMC Diabetes & Endocrinology Ltd.
Sponsor class: OTHER
First posted: 2019-02-12
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention 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.
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Time in range within 6 hours
timeFrame: 6 hours
Secondary outcomes:
measure: Change in glucose within 60 mins after high-intensity exercise starts
timeFrame: 60 mins
measure: Change in glucose within 120 mins after moderate-intensity exercise starts
timeFrame: 120 mins
measure: Time spent in hypoglycemia 24 hours after exercise
timeFrame: 24 hours
measure: Time in range 24 hours after exercise
timeFrame: 24 hours
measure: Time spent in hyperglycemia 24 hours after exercise
timeFrame: 24 hours
measure: Time in range in the last 4 weeks of each study phase
timeFrame: 4 weeks
measure: Frequency of hypoglycemia 24 hours after exercise
timeFrame: 24 hours
measure: Frequency of hypoglycemia in the last 4 weeks of each study phase
timeFrame: 4 weeks
measure: Change in Diabetes Medication Satisfaction (DiabMedSat) Score
timeFrame: 11 weeks
measure: Change in Hypoglycemia Fear Score
timeFrame: 11 weeks
measure: Change in TRIM-D Score
timeFrame: 11 weeks
Other outcomes:
Locations:
city: Toronto
country: Canada
facility: LMC Diabetes & Endocrinology Ltd.
state: Ontario
Study officials:
References:
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citation: Delvecchio M, Zecchino C, Salzano G, Faienza MF, Cavallo L, De Luca F, Lombardo F. Effects of moderate-severe exercise on blood glucose in Type 1 diabetic adolescents treated with insulin pump or glargine insulin. J Endocrinol Invest. 2009 Jun;32(6):519-24. doi: 10.1007/BF03346499.
citation: Yardley JE, Zaharieva DP, Jarvis C, Riddell MC. The "ups" and "downs" of a bike race in people with type 1 diabetes: dramatic differences in strategies and blood glucose responses in the Paris-to-Ancaster Spring Classic. Can J Diabetes. 2015 Apr;39(2):105-10. doi: 10.1016/j.jcjd.2014.09.003. Epub 2014 Dec 6.
citation: Riddell MC, Gallen IW, Smart CE, Taplin CE, Adolfsson P, Lumb AN, Kowalski A, Rabasa-Lhoret R, McCrimmon RJ, Hume C, Annan F, Fournier PA, Graham C, Bode B, Galassetti P, Jones TW, Millan IS, Heise T, Peters AL, Petz A, Laffel LM. Exercise management in type 1 diabetes: a consensus statement. Lancet Diabetes Endocrinol. 2017 May;5(5):377-390. doi: 10.1016/S2213-8587(17)30014-1. Epub 2017 Jan 24.
citation: Aronson R, Li A, Brown RE, McGaugh S, Riddell MC. Flexible insulin therapy with a hybrid regimen of insulin degludec and continuous subcutaneous insulin infusion with pump suspension before exercise in physically active adults with type 1 diabetes (FIT Untethered): a single-centre, open-label, proof-of-concept, randomised crossover trial. Lancet Diabetes Endocrinol. 2020 Jun;8(6):511-523. doi: 10.1016/S2213-8587(20)30114-5.