Optimal Insulin Correction Factor in Post- High Intensity Exercise Hyperglycemia in Adults With Type 1 Diabetes (FIT)

Study Overview
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Brief Summary
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The overall objective of this study is to investigate the glycemic response of a 0%, 50%, 100% and 150% bolus insulin correction (based on personal insulin correction factor) of post-exercise hyperglycemia in physically active adults with type 1 diabetes (T1D) using multiple daily injections (MDI) in a controlled, but clinically representative, experimental setting.

Detailed Description
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FIT is an open-label, repeated measures cross-over study. The overall objective of this study is to investigate the glycemic response of a 0%, 50%, 100% and 150% bolus insulin correction (based on personal insulin correction factor) of post-exercise hyperglycemia in physically active adults with type 1 diabetes (T1D) using multiple daily injections (MDI) in a controlled, but clinically representative, experimental setting. Following a 2 week screening phase, patients will enter an 8 week transition to insulin glargine U300 (Toujeo®) if on another basal insulin, in order to optimize their insulin dose and determine their individual insulin correction factor. The final phase of the study is the intervention phase, which consists of 4 separate visits. At each visit, the patient will perform 15 minutes of high intensity exercise in the morning. If they become hyperglycemic following exercise (blood glucose >8.0 mmol/L), they will receive one of four insulin correction doses (0% 50%, 100%, or 150% of their usual correction factor) in a randomized order. They will be monitored in the clinical pharmacology unit by study staff for the rest of the day and overnight. The patient will wear a continuous glucose monitor (CGM) during each intervention visit. The primary outcome of the study is the greatest net reduction in plasma glucose (YSI) following a 50%, 100% and 150% bolus insulin correction of post-exercise hyperglycemia, compared to no bolus insulin correction. Key secondary outcomes include the mean time spent in post-exercise hyperglycemia (>8.0 mmol/L), post-exercise euglycemia (4.0-8.0 mmol/L) and post-exercise hypoglycaemia (≤ 3.9 mmol/L) within 180 minutes and 24 hours following bolus insulin correction.

Official Title
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Optimal Insulin Correction Factor in Post- High Intensity Exercise Hyperglycemia in Adults With Type 1 Diabetes: The FIT Study

Conditions
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Diabetes Mellitus, Type 1

Intervention / Treatment
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* Drug: 50% bolus insulin correction
* Drug: 100% bolus insulin correction
* Drug: 150% bolus insulin correction
* Other: 0% bolus insulin correction


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria Male or female Clinical diagnosis of presumed autoimmune T1D Age 18-55 years, inclusive Duration of T1D ≥ 6 months Using MDI therapy for at least 6 months Fasting C-peptide value of < 0.7 ng/mL (0.23 nmol/L) at screening visit Patient must be willing to undergo an 8-week run-in phase prior to the study period where they will be required to use MDI therapy at least 4 times per day, and switch from their usual basal insulin to insulin glargine U300 Exercise regularly: i.e. ≥ 30 minutes of moderate or vigorous aerobic activity ≥ 3 times/week for a minimum of 90 minutes weekly VO2peak ≥32 ml/kg/min for females and ≥ 35 ml/kg/min for males HbA1c between 6.0-9.0% inclusive at screening visit. Insulin total daily dose (TDD) ≥ 30 U/day In good general health with no known conditions that could influence the outcome of the trial, and in the judgement of the Investigator is a good candidate for the study based on review of available medical history, physical examination and clinical laboratory evaluations Willing to adhere to the protocol requirements for the duration of the study Exclusion Criteria Pregnant or lactating Active diabetic retinopathy (proliferative diabetic retinopathy, or vitreous haemorrhage 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 run-in phase or study period Medications other than insulin that might impact outcome measures: Beta blockers Agents that affect hepatic glucose production such as beta adrenergic agonists and antagonists, 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
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: 0% Bolus Insulin Correction<br>0% Bolus Insulin Correction | Other: 0% bolus insulin correction<br>* Patients will receive no bolus insulin correction for post-exercise hyperglycemia<br>|
| Active Comparator: 50% Bolus Insulin Correction<br>50% Bolus Insulin Correction | Drug: 50% bolus insulin correction<br>* Patients will receive 50% of their usual bolus insulin correction for post-exercise hyperglycemia<br>|
| Active Comparator: 100% Bolus Insulin Correction<br>100% Bolus Insulin Correction | Drug: 100% bolus insulin correction<br>* Patients will receive 100% of their usual bolus insulin correction for post-exercise hyperglycemia<br>|
| Active Comparator: 150% Bolus Insulin Correction<br>150% Bolus Insulin Correction | Drug: 150% bolus insulin correction<br>* Patients will receive 150% of their usual bolus insulin correction for post-exercise hyperglycemia<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Reduction In Plasma Glucose (YSI) |  | 147 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Investigate Glycemic Response of a 0%, 50%, 100% and 150% Bolus Insulin Correction of Post-exercise Hyperglycemia Compared to no Bolus Insulin Correction |  | 147 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Diabetes, Exercise, Insulin