Flat and Circadian Insulin Infusion Rates in Continuous Subcutaneous Insulin Infusion

Study Overview
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Brief Summary
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Randomised controlled trial to contribute to the evidence base for the optimal initial insulin profile for adults with type 1 diabetes commencing insulin pump therapy.

Detailed Description
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Initiation of insulin pump therapy in people with type 1 diabetes requires conversion of a basal insulin dose, given as once or twice daily long-acting insulin, to a continuous basal infusion regimen. This conversion may be based on basal insulin dose only, or total daily insulin dose, and may result in a flat basal insulin profile or an initial variable basal rate. Initial variable basal rates aim to replicate circadian changes in insulin requirements and are derived from total basal insulin in adults over 24 years old, and from weight in adults aged 18 to 24 years. Initial rates were developed from 63 well-controlled people with type 1 diabetes over 14 years of age and have been assessed against a flat basal rate in a small randomised controlled trial with 12 participants. Mean glucose was lower in the circadian basal rate group with particular differences noted in the early morning when glucose rises were more pronounced in the flat basal rate group1. In 50 people with type 1 diabetes treated with insulin pump therapy, HbA1c was lower in those with lower basal rates at midnight, and in those with higher basal rates in the afternoon, suggesting a benefit of circadian patterns2. In 33 people with type 1 diabetes over 16 years of age basal rate distribution established at commencement of pump therapy did not alter over 6 months3. However, a 6 month cross-over study of circadian rates and oligophasic basal rates showed no difference in HbA1c4. Following initiation on insulin pump therapy basal rates are personalised to capillary blood and continuous interstitial fluid glucose monitoring. In adults with type 1 diabetes starting insulin pump therapy there are limited data to guide the optimal insulin profile to rapidly achieve target glucose and minimise healthcare professional input.

Official Title
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A Study of Flat and Circadian Insulin Infusion Rates in Continuous Subcutaneous Insulin Infusion (CSII) in Adults With Type 1 Diabetes

Conditions
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Type 1 Diabetes

Intervention / Treatment
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* Drug: Insulin (circadian)
* Drug: Insulin (flat rate)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adults ≥18 years of age Diagnosis of T1DM for > 1 year On MDI with decision made to commence CSII Structured education in previous 3 years HbA1c ≤ 75mmol/mol (9%) Stimulated c-peptide <200pmol/L No severe hypoglycaemia (defined as needing 3rd party assistance) in previous year Exclusion Criteria: Previous CSII Night or shift worker Recurrent severe hypoglycaemia Pregnant or planning pregnancy Breastfeeding Enrolled in other clinical trials Have active malignancy or under investigation for malignancy Addison's Disease Gastroparesis Autonomic neuropathy Concomitant use of GLP-1 analogues and gliptins Visual impairment Reduced manual dexterity

Ages Eligible for Study
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Minimum Age: 18 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: Supportive Care
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: circadian insulin infusion rates<br>Initial variable basal rates aim to replicate circadian changes in insulin requirements and are derived from total basal insulin in adults over 24 years old, and from weight in adults aged 18 to 24 years. | Drug: Insulin (circadian)<br>* Participant's own insulin adjusted to circadian infusion rates<br>|
| Active Comparator: flat rates<br>flat basal rate | Drug: Insulin (flat rate)<br>* Participant's own insulin set to flat basal rates<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Basal Insulin Rate | Absolute change in insulin basal rate over 24 hours after 3 rounds of basal rate testing (calculated by the sum of absolute changes for each 1 hour block compared with baseline) | over 24 hours after 3 rounds of basal rate testing |