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

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

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.

Study Overview

• Status: Unknown
• Conditions: Type 1 Diabetes Mellitus
• Intervention / Treatment: Drug: Insulin Degludec

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.

• Study Type: Interventional
• Enrollment (Anticipated): 30
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Ronnie Aronson, MD; Phone Number: 416-645-2929; Email: aronsonresearch@LMC.ca

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada, M4G 3E8
      • Recruiting
      • LMC Diabetes & Endocrinology Ltd.
      • Contact: Nichole Mckay, MSc

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: Usual CSII; Continue to use the established CSII insulin therapy
Experimental: Untethered CSII; 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; 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; Other Names: Tresiba

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: LMC Diabetes & Endocrinology Ltd.

Publications and helpful links

General Publications

• Doyle EA, Weinzimer SA, Steffen AT, Ahern JA, Vincent M, Tamborlane WV. A randomized, prospective trial comparing the efficacy of continuous subcutaneous insulin infusion with multiple daily injections using insulin glargine. Diabetes Care. 2004 Jul;27(7):1554-8. doi: 10.2337/diacare.27.7.1554.
• 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. Erratum In: Lancet Diabetes Endocrinol. 2017 May;5(5):e3.
• Binek A, Rembierz-Knoll A, Polanska J, Jarosz-Chobot P. Reasons for the discontinuation of therapy of personal insulin pump in children with type 1 diabetes. Pediatr Endocrinol Diabetes Metab. 2016 Feb 18;21(2):65-9. doi: 10.18544/PEDM-21.02.0026.
• Wong JC, Boyle C, DiMeglio LA, Mastrandrea LD, Abel KL, Cengiz E, Cemeroglu PA, Aleppo G, Largay JF, Foster NC, Beck RW, Adi S; T1D Exchange Clinic Network. Evaluation of Pump Discontinuation and Associated Factors in the T1D Exchange Clinic Registry. J Diabetes Sci Technol. 2017 Mar;11(2):224-232. doi: 10.1177/1932296816663963. Epub 2016 Sep 25.
• Benbenek-Klupa T, Matejko B, Klupa T. Metabolic control in type 1 diabetes patients practicing combat sports: at least two-year follow-up study. Springerplus. 2015 Mar 17;4:133. doi: 10.1186/s40064-015-0919-5. eCollection 2015.
• 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.
• 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.
• 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.

Study record dates

Study Major Dates

• Study Start (Actual): May 15, 2018
• Primary Completion (Anticipated): April 30, 2019
• Study Completion (Anticipated): June 30, 2019

Study Registration Dates

• First Submitted: July 26, 2018
• First Submitted That Met QC Criteria: February 11, 2019
• First Posted (Actual): February 12, 2019

Study Record Updates

• Last Update Posted (Actual): February 12, 2019
• Last Update Submitted That Met QC Criteria: February 11, 2019
• Last Verified: February 1, 2019

More Information

Terms related to this study

• Keywords: Exercise; Insulin Degludec; Continuous Subcutaneous Insulin Infusion (CSII); Continuous glucose monitoring (CGM)
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Immune System Diseases; Autoimmune Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 1; Hypoglycemic Agents; Physiological Effects of Drugs; Insulin
• Other Study ID Numbers: FIT Untethered

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No