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Completed

NCT Number: NCT00993473

6-month Comparison of Morning Lantus Versus Neutral Protamine Hagedorn Insulin in Young Children With Type 1 Diabetes

The primary study objective was to compare the rate of "all hypoglycemia" (composite outcome of the following hypoglycemia events: symptomatic hypoglycemia episodes, low continuous glucose monitoring system (CGMS) excursions confirmed by fingerstick blood glucose (FSBG), low FSBG readings performed at other times) between children treated with Lantus (insulin glargine) and Neutral Protamine Hagedorn (NPH) insulin.

Secondary objectives were to compare insulin glargine and NPH in terms of:

* rates of specific types of hypoglycemia: symptomatic, severe, nocturnal, nocturnal symptomatic, and severe nocturnal symptomatic hypoglycemia * HbA1c change from baseline to end-of-treatment, and HbA1c at end-of-treatment * percentage of patients reaching HbA1c less than 7.5% (target value) at end of treatment * average blood glucose over whole trial and at end of trial, as estimated by continuous glucose monitoring (CGM), and blood glucose variability

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Key information

Conditions

Type 1 Diabetes Mellitus Autoimmune Diseases Diabetes Mellitus Diabetes Mellitus, Type 1 Endocrine System Diseases Glucose Metabolism Disorders Immune System Diseases Metabolic Diseases Nutritional and Metabolic Diseases

Age range

1 year–6 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 3

Primary location

Sanofi-Aventis Investigational Site Number 040001, Vienna, Austria

Loading trial locations.

About this study

Screening phase: 2 to 4 weeks

Treatment phase: 24 weeks

At randomization, patients were stratified with respect to their baseline HbA1c level (<8.5% or ≥8.5%) and hypoglycemic event rate (number of CGMS hypoglycemic excursions <0.5 or ≥0.5 events per 24 hours). Following randomization, trial basal insulin was initiated and up-titrated within the first 12 weeks to reach a stable dose.

Follow-up phase: 2 weeks

All Phases: 28 to 30 weeks

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Pediatric patients with type 1 diabetes mellitus aged at least one year to less than 6 years at screening, for whom signed written informed consent has been obtained from parent or legal guardian to participate in the study

Exclusion criteria

  • Diagnosis of type 1 diabetes for less than one year
  • HbA1c at screening >12% or <6%
  • Diabetes other than type 1 diabetes
  • Parents and patients not willing to undergo all study assessments and treatments, including home blood glucose monitoring, Continuous Glucose Monitoring System (CGMS) sensor placement and maintenance both at the site and at home, multiple daily insulin injections, and visits, as dictated by the protocol (if a telephone is not available patients may undergo all visits in person)
  • Patients and families for whom 6 days in total (not necessarily continuous) of useable CGMS data cannot be obtained (either by home sensor replacement, or by sensor replacement at the site at additional screening visits if needed) during the screening CGMS evaluations between Visit 2 and the randomization visit
  • Patients treated with insulin pump therapy during the two months prior to screening
  • History of primary seizure disorder
  • History of severe hypoglycemic episode accompanied by seizure and/or coma, or diabetic ketoacidosis leading to hospitalization or to care in the emergency ward, in the 2 months prior to the screening visit
  • Need for chronic treatment with acetaminophen (paracetamol)-containing medications
  • Serum creatinine > 2.0mg/dL at screening
  • Serum ALT or AST greater than 3x upper limit of normal for the patient's age and gender, at screening
  • Hemoglobin < 10g/dL, or platelet count less than 100,000/cu mm, at screening
  • Treatment with any pharmacologic anti-hyperglycemic oral agent for more than 3 months at any time
  • Treatment with any non-insulin antihyperglycemic medication (eg, Symlin®) for the 3 months prior to screening
  • Treatment with systemic glucocorticoids within the month prior to screening

Above information not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.

Treatment and study plan

Insulin glargine (HOE901)

Drug

100 U/mL commercial solution for injection available as both disposable pen devices Solostar® each containing 300 U and as 10 mL vials each containing 1000 U

Dose: titrated to achieve the following glycemic targets without hypoglycemia:

  • Fasting blood glucose (BG) between 90 and 145 mg/dL (5.0 to 8.0 mmol/L), inclusive,
  • Bedtime BG between 120 and 180 mg/dL (6.7 to10.0 mmol/L), inclusive,
  • Nocturnal BG between 80 and 162 mg/dL (4.4 to 9.0 mmol/L), inclusive; and
  • HbA1c <7.5%.

Other names: Lantus®

Neutral Protamine Hagedorn (NPH) insulin

Drug

NPH insulin 100 U/mL commercial (Huminsulin Basal) solution for injection available as both disposable pen devices (Huminsulin Basal Pen) each containing 300 U and as 10 mL vials each containing 1000 U

Dose: titrated to achieve glycemic targets as described above for insulin glargine

Insulin Lispro

Drug

Insulin lispro used as the principal bolus insulin; regular human insulin permitted. Administration: multiple injection before meals and/or at bedtime at the discretion of the Investigator.

Other names: Humalog®

Primary outcomes

  1. Event Rate of "All Hypoglycemia" Defined as the Total Number of Episodes Divided by the Total Duration of the On-treatment Period in Years (Events Per Patient-year)

    Time frame: 6 months

    The rate of "all hypoglycemia" was calculated from "all hypoglycemia" episodes which occurred during the 24-week on-treatment period and consisted of: - symptomatic hypoglycemia episodes validated by the study investigator based on entries in patients' diaries, - low continuous glucose monitoring system (CGMS) excursions (interstitial glucose <70 mg/dL [3.9 mmol/L]) confirmed by fingerstick blood glucose (FSBG) <70 mg/dL, - low FSBG readings (values <70 mg/dL) performed at other times.

Secondary outcomes

  1. Event Rate of Symptomatic Hypoglycemia (Individual Component of Primary Endpoint) Defined as the Total Number of Episodes Divided by the Total Duration of the On-treatment Period in Years (Events Per Patient-year)

    Time frame: 6 months

    Symptomatic hypoglycemia: any event with clinical symptoms considered to result from hypoglycemia, validated by the study investigator based on data from patient diaries.

  2. Event Rate of Severe Symptomatic Hypoglycemia Defined as the Total Number of Episodes Divided by the Total Duration of the On-treatment Period in Years

    Time frame: 6 months

    Severe symptomatic hypoglycemia: any event with clinical symptoms considered to result from a hypoglycemic episode for which the patients required the assistance of a third party (ie, other than the patient, or a parent/usual caregiver; eg, from emergency personnel), because the patients/parents could not treat the event with acute neurological impairment directly resulting from the hypoglycemic event. The occurrence of seizure, coma, unconsciousness, or the use of glucagon, were also to qualify a hypoglycemic episode as severe.

  3. Event Rate of Nocturnal Hypoglycemia Defined as the Total Number of "All Hypoglycemia" Episodes Divided by the Total Duration of the On-treatment Period in Years

    Time frame: 6 months

    Nocturnal hypoglycemia: any event from the "all hypoglycemia" total that occurred between 23:00 and 07:00 hours.

  4. Event Rate of Nocturnal Symptomatic Hypoglycemia Defined as the Total Number of Episodes Divided by the Total Duration of the On-treatment Period in Years

    Time frame: 6 months

    Nocturnal symptomatic hypoglycemia: any symptomatic hypoglycemic event that occurred between 23:00 and 07:00 hours.

  5. Event Rate of Severe Nocturnal Hypoglycemia Defined as the Total Number of Episodes Divided by the Total Duration of the On-treatment Period in Years

    Time frame: 6 months

    Severe nocturnal symptomatic hypoglycemia: any severe symptomatic hypoglycemic event that occurred between 23:00 and 07:00 hours.

  6. Glycosylated Hemoglobin A1c (HbA1c): End of Treatment and Change From Baseline to End of Treatment

    Time frame: baseline, 6 months

  7. Glycosylated Hemoglobin A1c (HbA1c): End of Treatment and Change From Baseline to End of Treatment (ANCOVA Estimates)

    Time frame: baseline, 6 months

    Assessed using an analysis of covariance (ANCOVA) model with treatment, and randomization strata (baseline number of CGM hypoglycemic excursions <0.5 events/24hours or ≥0.5 events/24 hours, and baseline HbA1c <8.5% or ≥8.5%) as fixed effects, and using the baseline value as covariate.

  8. Percentage of Patients Reaching HbA1c Target of Less Than 7.5% at the End of Treatment Visit

    Time frame: 6 months

    Percentage of patients reaching International Society for Pediatric and Adolescent Diabetes (ISPAD)-recommended goals of Glycosylated Hemoglobin A1c <7.5% at the end of treatment visit.

  9. Average Daily Blood Glucose (BG) Based on CGMS Values: End of Treatment and Change From Baseline to End of Treatment

    Time frame: baseline, 6 months

Other outcomes

  1. Number of Patients With Different Types of Hypoglycemia Events

    Time frame: 6 months

    Definitions of the different types of hypoglycemia events provided in the outcome measure description of the corresponding event rates.

  2. Percent of Blood Glucose (BG) Within the Range of 70 - 180 mg/dL (3.9-10 mmol/L)

    Time frame: 6 months

    Calculated for each patient as the percent of all on-treatment CGMS values falling within the range of 70 - 180 mg/dL (3.9 - 10 mmol/L) inclusive.

  3. Blood Glucose Variability Based on All On-treatment CGMS Values

    Time frame: 6 months

    Calculated for any given patient as the standard deviation (SD) of all CGMS interstitial glucose values recorded over all CGMS placements.

  4. Nocturnal Blood Glucose Variability Based on All On-treatment CGMS Values

    Time frame: 6 months

    Calculated for any given patient as the standard deviation (SD) of all CGMS interstitial glucose values recorded during the nocturnal time period (between 23:00 and 07:00 hours).

Sponsors and collaborators

Lead sponsor

Sanofi

Industry

Registry information

Official study title

A 24-week, Randomized, Open-label, Parallel Group Multinational Comparison of Lantus® (Insulin Glargine) Given in the Morning as Once-a-day Basal Insulin Versus Neutral Protamine Hagedorn (NPH) Insulin, in Children With Type 1 Diabetes Mellitus Aged at Least 1 Year to Less Than 6 Years

Acronym: PRESCHOOL

Important dates

Study start
2009
Primary completion
2011
Study completion
2011
First posted
Oct 12, 2009
Registry last updated
Jun 27, 2012

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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