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

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

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.

Study Overview

• Status: Recruiting
• Conditions: Type 1 Diabetes
• Intervention / Treatment: Drug: Humulin N plus Humulin R; Drug: premix insulin human isophane suspension and insulin human

• Study Type: Interventional
• Enrollment (Estimated): 20
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Yempabou Sagna; Phone Number: +22671221937; Email: my_sagna@yahoo.fr

Study Locations

• Burkina Faso
  • Houet
    • Bobo-Dioulasso, Houet, Burkina Faso
      • Recruiting
      • CHU Souro Sanou
      • Contact: Abraham Bagbila, MD; Phone Number: +22671665138
  • Kadiogo
    • Ouagadougou, Kadiogo, Burkina Faso
      • Recruiting
      • CHU de Tengandogo
      • Contact: Lassina Séré, MD; Phone Number: +22671483284
    • Ouagadougou, Kadiogo, Burkina Faso
      • Recruiting
      • CHU Yalgado Ouedraogo
      • Contact: Yempabou Sagna, MD
      • Contact: Pouikomba Patrice Savadogo, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 5 years to 18 years (Child, Adult)
• Accepts Healthy Volunteers: No

Description

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.

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
Active Comparator: Humulin N plus Humulin R; 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; 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
Experimental: Premix human isophane suspension plus insulin human injection; 10 subjects will receive premix insulin human isophane suspension and insulin human injection twice daily	Drug: premix insulin human isophane suspension and insulin human; 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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

Collaborators and Investigators

• Sponsor: Université NAZI BONI
• Collaborators: Juvenile Diabetes Research Foundation; International Society for Pediatric and Adolescent Diabetes; Société de Médecine Interne du Burkina Faso; Association pour la Formation, la Recherche et l'Education sur le Diabète, Burkina Faso

Study record dates

Study Major Dates

• Study Start (Actual): June 15, 2023
• Primary Completion (Estimated): April 15, 2024
• Study Completion (Estimated): June 15, 2024

Study Registration Dates

• First Submitted: March 1, 2023
• First Submitted That Met QC Criteria: March 12, 2023
• First Posted (Actual): March 14, 2023

Study Record Updates

• Last Update Posted (Actual): July 10, 2023
• Last Update Submitted That Met QC Criteria: July 6, 2023
• Last Verified: July 1, 2023

More Information

Terms related to this study

• 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; Insulin, Globin Zinc; Insulin, Isophane; Isophane Insulin, Human; Isophane insulin, beef
• Other Study ID Numbers: 2023-SOMIBF-01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; CSR

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