Comparative Efficacy of a Two Daily Mixed Insulin Injection Versus a Basal-bolus Scheme With Human Insulin

Study Overview
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Brief Summary
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The goal of this clinical trial is to compare glycemic control and variability between children and adolescents with type 1 diabetes treated by a two daily injection of premixed human insulin (Humulin 30/70) and those who have a basal bolus scheme (Humulin N + Humulin R) in a resources limited setting. The main question it aims to answer is: what is the effectiveness of premixed human insulin on glycemic control? Ten participants will be randomized initially to premix insulin human isophane suspension and insulin human injection (Humulin 30/70) twice daily, and 10 persons to insulin human isophane suspension (Humulin N) twice daily plus regular human insulin (Humulin R) before meals. At the end of the initial 16-wk treatment (period 1), all patients will be crossed over to the alternate treatment arm for an additional 16 wk (period 2). Insulin doses will be adjusted weekly by the clinical site according to a prespecified insulin intensification algorithm to achieve target fasting [<110 mg/dl (6.1 mmol/liter)], bedtime [<130 mg/dl (7.2 mmol/liter)], and premeal [<110 mg/dl (6.1 mmol/liter)] glucose levels until HbA1c was below 7.0%. Subjects will receive training on the FreeStyle Libre CGMS System, electronic hand-held personal digital assistant (e-diary), and self-monitoring of blood glucose (SMBG), including recording glucose, insulin doses, and symptoms of hypo- or hyperglycemia.

Official Title
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Comparative Efficacy of a Two Daily Mixed Insulin Injection Versus a Basal-bolus Scheme With Human Insulin in a Limited Resources Setting: a Multicenter Randomized Controlled Crossover Clinical Trial

Conditions
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Type 1 Diabetes

Intervention / Treatment
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* Drug: premix insulin human isophane suspension and insulin human
* Drug: Humulin N plus Humulin R


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female 5 - 18 years of age Be diagnosed for at least 1 year at the date of inclusion. Have been regular at consultations during the last 12 years preceding inclusion (at least 3 visits) Willing and able to inject insulin human isophane and multi-day dosing of rapid acting human insulin. Willing and able to perform self-monitoring of blood glucose (SMBG) four times a day and continuous glucose monitoring (CGMS) for 48 hours at three time periods during the study Have (patient or guardian) a minimum 4 years primary school level Have (patient or guardian) a connected cellphone that can install the free FreeStyle link application and use connected messaging app Exclusion Criteria: pregnant or lactating females opposition to participating in the study residing outside the towns where the care centers are located Any disease or condition (including abuse of illicit drugs, prescription medicines or alcohol) that in the opinion of the investigator or sponsor may interfere with the study compliance and completion of the study.

Ages Eligible for Study
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Minimum Age: 5 Years
Maximum 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: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Humulin N plus Humulin R<br>10 subjects will receive insulin human isophane suspension (Humulin N) twice daily plus regular human insulin (Humulin R) before meals | Drug: Humulin N plus Humulin R<br>* Sequence (Humulin N + Humulin R first, then Premix): Subjects randomized to this sequence will receive basal bolus insulin scheme with Humulin N (twice daily) and Humulin R (before meals) for 16 weeks. After the first 16 weeks, subjects will cross over to the Premix sequence for a further treatment of 16 weeks<br>|
| Experimental: Premix human isophane suspension plus insulin human injection<br>10 subjects will receive premix insulin human isophane suspension and insulin human injection twice daily | Drug: premix insulin human isophane suspension and insulin human<br>* Sequence (Premix first, then Humulin N + Humulin R): Subjects randomized to this sequence will receive premix insulin, twice per day for 16 weeks. After the first 16 weeks, subjects will cross over to the Humulin N plus Humulin R sequence for a further treatment of 16 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To compare improvements from baseline in patient HbA1c when aggressively treated with insulin human isophane plus rapid acting human insulin vs treatment with Premix human insulin |  | 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| frequency of hypo events (throughout the trial) | weekly frequency of hypo events and time below range | 8 months | 
| Quality of life score (baseline, week 32) (Using the Pediatric Quality of Life Inventory, 3.2 Diabetes module.) | The PedsQL 3.2 Diabetes Module is composed of 33 items comprising 5 dimensions for ages 8- 45 years and 32 items for ages 2-7 years. Items are reversed scored and linearly transformed to a 0-100 scale. Higher scores indicate lower problems | 8 months | 
| correlation between patient QoL and glucose variability as measured by CGMS (baseline, week 16 and week 32) |  | 8 months |