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

LMC Diabetes & Endocrinology Ltd.

Status and phase: Unknown; Phase 4

Conditions: Diabetes Mellitus, Type 1

Treatments: Drug: 150% bolus insulin correction; Other: 0% bolus insulin correction; Drug: 100% bolus insulin correction; Drug: 50% bolus insulin correction

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT03057470

FIT

Details and patient eligibility

About

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.

Full description

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.

Enrollment: 18 estimated patients

Sex: All

Ages: 18 to 55 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: None (Open label)

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18 participants in 4 patient groups

0% Bolus Insulin Correction

Active Comparator group

Description:

0% Bolus Insulin Correction

Treatment:

Other: 0% bolus insulin correction

50% Bolus Insulin Correction

Active Comparator group

Description:

50% Bolus Insulin Correction

Treatment:

Drug: 50% bolus insulin correction

100% Bolus Insulin Correction

Active Comparator group

Description:

100% Bolus Insulin Correction

Treatment:

Drug: 100% bolus insulin correction

150% Bolus Insulin Correction

Active Comparator group

Description:

150% Bolus Insulin Correction

Treatment:

Drug: 150% bolus insulin correction