Human Versus Analogue Insulin for Youth With Type 1 Diabetes in Low-Resource Settings

Phase 4

Completed

Conditions: Diabetes Mellitus, Type 1
Type 1 Diabetes

Interventions: Drug: Insulin Glargine
Drug: NPH or premixed 70/30 (human insulin)

Registration Number: NCT05614089

Lead Sponsor: Jing Luo

Brief Summary: The primary objective of this trial is to determine whether insulin glargine reduces the risk of serious hypoglycemia or improves Time in Range at 6 months when compared against standard of care human insulin (e.g. NPH or premixed 70/30) among youth living with type 1 diabetes (T1D) in low resource settings.

Detailed Description: Long-acting insulin analogues have become a de-facto standard of care for patients with T1D living in high-income countries. Unfortunately, insulin analogues remain unavailable or unaffordable for much of the global population. In both 2017 and 2019, applications to add long-acting insulin analogues to the WHO's Model List of Essential Medicines (EML) were rejected due to insufficient evidence of superiority and an unfavorable cost-effectiveness profile when compared against older, less expensive, human insulins (e.g., NPH insulin and premixed 70/30 insulin). In 2021, long-acting insulin analogues were added to the EML but the decision remains controversial since the WHO concluded that "magnitude of clinical benefit of long-acting insulin analogues over human insulin for most clinical outcomes was small." Moreover, studies that compare long-acting insulin analogues versus human insulins conducted in high-income settings may not generalize to children and young adults living with T1D in very low-resource settings.

To address this unmet need, Pitt has partnered with Brigham and Women's Hospital, The London School of Hygiene and Tropical Medicine, the Clinton Health Access Initiative and Life For a Child to conduct a randomized controlled trial comparing insulin glargine, a long-acting analogue insulin, against intermediate human insulin among 400 children and young adults living with T1D in a lower resource setting.

Note: In preparation for results submission, we made minor changes to the outcomes sections to reflect what is listed in the protocol.

For Primary Outcomes #1 and #2, and Secondary Outcomes #3,#4, #5, #7, #8: we added 12 months measurements (in addition to the 6 months measurement). We updated Secondary Outcome #9 to specify the PedsQL Diabetes Symptoms Score. We added Secondary Outcome #10 to include the PedsQL Diabetes Management Score. We added Secondary Outcome #11 for ITSQ scores.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 400

Inclusion Criteria

Children and young adults (age 7-25)
Have a clinical diagnosis of type 1 diabetes (T1D)

Exclusion Criteria

Prior use of any insulin analogue
Patients (or parents for children <18 years old) who refuse to or cannot provide informed consent
Who are currently pregnant or plan to become pregnant over the next year
Who have previously used a continuous glucose monitor (CGM) for glucose monitoring
Who were first diagnosed with T1D less than 12 months ago
Who is diagnosed with severe malnutrition

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Glargine	Insulin Glargine	Insulin glargine (long-acting insulin analogue)
NPH or premixed 70/30 (human insulin)	NPH or premixed 70/30 (human insulin)	NPH or premixed 70/30 (human insulin)

Primary Outcome Measures

Name	Time	Method
Time-in-serious Hypoglycemia	6 and 12 months after randomization	% time spent less than 54 mg/dl averaged across all daily measures. For 6-month outcome, these data were averaged across two CGM sensors (placed at 6 and 6.5 months). For 12-month outcome, these data were from one CGM sensor placed at 11.5 months.
Time-in-range (TIR)	6 and 12 months after randomization	% time spent between 70 and 180mg/dl inclusive averaged across all daily measures. For 6-month outcome, these data were averaged across two CGM sensors (placed at 6 and 6.5 months). For 12-month outcome, these data were from one CGM sensor placed at 11.5 months.

Secondary Outcome Measures

Name	Time	Method
Time-in-hypoglycemia	6 and 12 months after randomization	% time spent less than 70mg/dl averaged across all daily measures. For 6-month outcome, these data were averaged across two CGM sensors (placed at 6 and 6.5 months). For 12-month outcome, these data were from one CGM sensor placed at 11.5 months.
Time-above-range	6 and 12 months after randomization	% time spent greater than 180mg/dl averaged across all daily measures. For 6-month outcome, these data were averaged across two CGM sensors (placed at 6 and 6.5 months). For 12-month outcome, these data were from one CGM sensor placed at 11.5 months.
Nocturnal Hypoglycemic Events	6 and 12 months after randomization	Number of events defined as ≥15 minutes in duration \<70 mg/dL between midnight and 6:00 am; specifically, at least 2 sensor values \<70 mg/dL that are ≥15 minutes apart plus no intervening values ≥70 mg/dL For 6-month outcome, these data were averaged across two CGM sensors (placed at 6 and 6.5 months). For 12-month outcome, these data were from one CGM sensor placed at 11.5 months.
Glycemic Control (HbA1c)	baseline, 3, 6, 9 and 12 months after randomization	Mean HbA1c lab result reported as percent, which is typically how it is reported.
Rate of Severe Hypoglycemic Events	6 and 12 months after randomization	Severe hypoglycemic events (requiring assistance of another person to correct) reported by participant per 1000 person-years
Rate of Diabetic Ketoacidosis (DKA)	6 and 12 months after randomization	Hospitalization or Emergency Room Visit (serious adverse event) with primary diagnosis of Diabetic Ketoacidosis. This was measured by self-report and confirmed through review of hospital records
Pediatric Quality of Life Inventory 3.2 Diabetes Module (PedsQL 3.2 DM) Diabetes Symptoms Score	Baseline and at 6 and 12 months after randomization	Mean PedsQL 3.2 DM Diabetes Symptoms score. PedsQL 3.2 DM Diabetes Symptoms scale is composed of 15 items. All items use the same 5-point Likert response scale, with responses ranging from "never" (0) to "almost always" (4). Items are reverse scored and transformed on a scale ranging from 0 to 100. The score is the sum of all the items over the number of items answered. Higher scores indicate fewer diabetes symptoms and therefore improved diabetes-specific health-related quality of life (D-HRQoL).
Pediatric Quality of Life Inventory 3.2 Diabetes Module (PedsQL 3.2 DM) Diabetes Management Score	Baseline and at 6 and 12 months after randomization	Mean PedsQL 3.2 DM Diabetes Management score. PedsQL 3.2 DM Diabetes Management scale is composed of 18 items. All items use the same 5-point Likert response scale, with responses ranging from "never" (0) to "almost always" (4). Items are reverse scored and transformed on a scale ranging from 0 to 100. Higher scores indicate fewer diabetes management problems and therefore improved D-HRQoL.
Insulin Treatment Satisfaction Questionnaire (ITSQ) Scores	Baseline and at 6 and 12 months after randomization	The ITSQ is composed of 22 items. A total 22-item score is reported, and the items are also divided into five subscales: Regimen Inconvenience (5 items), Lifestyle Flexibility (3 items), Glycemic Control (3 items), Hypoglycemic Control (5 items), and Insulin Delivery Device Satisfaction (6 items). Items use 7-point Likert scale responses, ranging from 1 (positive, e.g. "No bother at all") to 7 (negative, e.g. "A tremendous bother"), though the specific response labels vary by question. Items were reverse scored and transformed to range from 0 to 100. Higher scores indicate higher treatment satisfaction.

Trial Locations

Locations (3): BIRDEM Hospital
🇧🇩
Dhaka, Bangladesh
Bugando Medical Center
🇹🇿
Mwanza, Tanzania
Sekou-Toure Hospital
🇹🇿
Mwanza, Tanzania
BIRDEM Hospital
🇧🇩Dhaka, Bangladesh