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

Human Versus Analogue Insulin for Youth With Type 1 Diabetes in Low-Resource Settings: A Randomized Controlled Trial

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Diabetes Mellitus, Type 1; Type 1 Diabetes
• Intervention / Treatment: Drug: Insulin Glargine; Drug: NPH or premixed 70/30 (human insulin)

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.

• Study Type: Interventional
• Enrollment (Estimated): 400
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Jing Luo, MD, MPH; Phone Number: +1(412) 383-0627; Email: luoj@pitt.edu

Study Locations

• Bangladesh
  • Dhaka, Bangladesh
    • BIRDEM Hospital
• Tanzania
  • Mwanza, Tanzania
    • Bugando Medical Center
  • Mwanza, Tanzania
    • Sekou-Toure Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 7 years to 25 years (Child, Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

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

Exclusion Criteria:

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Glargine; Insulin glargine (long-acting insulin analogue)	Drug: Insulin Glargine; Formulation: Available as a clear liquid in a glass cartridge (1 cartridge =3ml=300 units). Route: Reusable pen Amount of each dose: varies depending on baseline basal insulin needs Dose escalation scheme: Participants randomly assigned to glargine will start with a dose that is generally equal to 80% of their total basal human insulin dose prior to the switch (per ISPAD guidelines and the switching guide developed by Life for a Child with the guidance of Dr. Ragnar Hanas and two other ISPAD members familiar with less-resourced settings). Frequency of dose: once per day (usually administered before bedtime)
Active Comparator: NPH or premixed 70/30 (human insulin)	Drug: NPH or premixed 70/30 (human insulin); Drug: NPH or Premixed 70/30 Formulation: Available as a liquid in a glass vial or glass cartridge (10ml=1000IU). Route: Bangladesh = syringes or reusable pens; Tanzania = disposable pens Subcutaneous injection using insulin syringe and needle Amount of each dose: varies depending on baseline basal insulin needs (per usual care or treating clinician) Frequency of dose: once or twice per day (per usual care or treating clinician) Duration of therapy: 12 months Participants in both groups will receive the same frequency of blood glucose testing and same intensity of education and counseling (e.g. titration advice according to fasting glucose targets and strategies to avoid hypoglycemia). Participants in both groups will have equal access to test strips (sufficient to test up to 5 times per day during the active titration phase and after 3 times/day).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time-in-serious hypoglycemia	% spent less than 54mg/dl, averaged across all daily measures averaged across two CGM sensors	6 months after randomization
Time-in-range (TIR)	% between 70 and 180mg/dl inclusive, averaged across two CGM sensors	6 months after randomization

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time-in-hypoglycemia	% spent less than 70mg/dl	6 months after randomization
Time-above-range	% spent greater than 180mg/dl	6 months after randomization
Nocturnal hypoglycemic events	Number of events (defined as >=15mins in duration < 70mg/dl) between 1200 and 0600	6 months after randomization
Glycemic control (HbA1c)	Mean HbA1c lab result	baseline, 3, 6, 9 and 12 months after randomization
Rate of severe hypoglycemic events	Events requiring the assistance of an external third party person	6 months after randomization
Rate of Diabetic Ketoacidosis	Hospitalization or Emergency Room Visit with primary diagnosis of Diabetic Ketoacidosis. This will be measured by self-report and confirmed through review of hospital records	6 months after randomization
Quality of Life (e.g. PedsQL Pediatric Quality of Life Inventory)	The PedsQLTM 3.2 Diabetes Module is composed of 33 items comprising 5 dimensions for ages 8- 45 years. Items are scaled on a 5-point scale from 0 (never) to 4 (almost always). Scores are transformed on a scale range from 0 to 100. The total score is the sum of all the items over the number of items answered on all scales.	Baseline and at 6 and 12 months after randomization

Collaborators and Investigators

• Sponsor: Jing Luo
• Collaborators: The Leona M. and Harry B. Helmsley Charitable Trust
• Investigators: Principal Investigator: Jing Luo, MD, MPH, University of Pittsburgh

Study record dates

Study Major Dates

• Study Start (Actual): March 15, 2023
• Primary Completion (Estimated): June 14, 2024
• Study Completion (Estimated): December 14, 2024

Study Registration Dates

• First Submitted: October 28, 2022
• First Submitted That Met QC Criteria: November 4, 2022
• First Posted (Actual): November 14, 2022

Study Record Updates

• Last Update Posted (Actual): March 12, 2024
• Last Update Submitted That Met QC Criteria: March 6, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: Tanzania; Type 1 Diabetes; Bangladesh; Insulin Glargine; Insulin Analogue; Human Insulin; Iraq
• 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 Glargine
• Other Study ID Numbers: STUDY21110122

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: De-identified, summary level data will be shared with other researchers, upon request.
• IPD Sharing Time Frame: 2 years after conclusion of study
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes