Comparing the Metabolic Control of Once to Twice-daily Insulin Detemir Injections

Comparing the Metabolic Control of Once to Twice-daily Insulin Detemir Injections in Children and Adolescence With Type 1 Diabetes Mellitus.

An open-label, treat to target, intervention study in order to compare the metabolic control of once to twice-daily insulin Detemir injections in children and adolescence with type 1 diabetes mellitus.

All eligible patients will be assigned to receive insulin Detemir once daily before breakfast. Short acting insulin analog, Novorapid, will be used for mealtime insulin. The starting dose of insulin Detemir will be individually determined.Based on self-measured fasting blood glucose levels, insulin doses will be titrated throughout the trial, aiming at pre-breakfast and premeal concentrations of 90-180 mg/dl for subjects aged 6-12 years and 80-130 mg/dl for subjects aged 13-18 years.Patients that after 4 weeks titration phase will not achieve the target blood glucose and up titration of insulin Detemir cannot be done, due to hypoglycemic episodes would be switched to treatment consist of twice daily insulin Detemir. If the target blood glucose are not achieved at the end of the 4 weeks titration phase, but further up titration is possible and patient does not suffer from hypoglycemic episodes, the titration period would be extended and patient would not be switched to treatment with 2 injections of insulin Detemir.When achieving blood glucose targets patient will continue until study end on the maintenance phase.

Study Overview

• Status: Completed
• Conditions: Type 1 Diabetes Mellitus
• Intervention / Treatment: Drug: Levemir (insulin detemir); Drug: Levemir twice a day

Detailed Description

An open label,treat to target, prospective, intervention study in order to compare the metabolic control of once to twice-daily insulin detemir injections in children and adolescence with type 1 diabetes mellitus.

Study objectives:

1. To assess the efficacy and safety of insulin detemir therapy (once or twice daily) using a treat to target titration protocol for initiating and maintaining therapy in children and adolescents with type 1 diabetes.
2. To evaluate the percentage of patients That will achieve a reduction of 0.5% of HbA1c from baseline to end of study evaluation.
3. To evaluate Incidence of sever, nocturnal, symptomatic and asymptomatic hypoglycemia and glucose excursions of both hyper and hypoglycemia as measured by the area under the curve determined by the CGMS technique.

Treatment plan:

Patients will be assigned to receive insulin detemir once daily before breakfast. Short acting insulin analog , Novorapid, will be used for mealtime insulin. The starting dose of insulin detemir will be individually determined. Based on self-measured fasting blood glucose levels, insulin doses will be titrated throughout the trial, aiming at pre breakfast and premeal concentrations of 90-180 mg/dl for subjects aged 6-12 years and 80-130 mg/dl for subjects aged 13-18 years.

Patients that after 4 weeks titration phase will not achieve the target blood glucose and up titration of insulin Detemir cannot be done, due to hypoglycemic episodes, would be switched to treatment consist of twice daily insulin Detemir.

If the target blood glucose are not achieved at the end of the 4 weeks titration phase, but further up titration is possible and patient does not suffer from hypoglycemic episodes, the titration period would be extended and patient would not be switched to treatment with 2 injections of insulin Detemir.

• Study Type: Interventional
• Enrollment (Anticipated): 50
• Phase: Phase 4

Contacts and Locations

Study Locations

• Israel
  • Petach-Tikva, Israel
    • Schneider Children's Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 6 years to 18 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Informed consent obtained before any trial related activity
2. Children with type 1 diabetes who have been treated with insulin for at least 12 months prior to the study.
3. Age > 6 years and < 18 years
4. HbA1c > 7.7%
5. Ability and willingness to accept the study conditions and to inject insulin detemir

Exclusion Criteria:

1. Impaired renal function or current renal dialysis.
2. Acute or chronic metabolic acidosis, including diabetic ketoacidosis.
3. Known hypoglycemia unawareness.
4. Known or suspected allergy to trial products.
5. Clinical evidence of active liver disease or impaired hepatic function
6. Participation in another study (with study drug) within the last 3 months prior to this trial.
7. Significant concomitant disease likely to interfere with glucose metabolism
8. Proven eating disorders
9. Malignancy within the last 5 years
10. History of repeated severe hypoglycemia within the last year.
11. Known diabetes retinopathy

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 1; once a day	Drug: Levemir (insulin detemir); Levemir once a day
Experimental: 2; twice a day	Drug: Levemir twice a day; Levemir twice a day

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
HbA1C	at screening visit, at the middle of the study, at the end of the study and prior to sweetching to twice daily treatment
SBGM	4-8 times a day
CGMS	72 hours prior to switching to twice daily treatment and at the end of study
Total daily basal and bolus insulin	will be calculated every visit

Secondary Outcome Measures

Outcome Measure	Time Frame
documentation of hypoglycemic and hyperglycemic episodes	diary will be collected every visit

Collaborators and Investigators

• Sponsor: Rabin Medical Center
• Investigators: Principal Investigator: Moshe Phillip, Professor, Schneider Children Medical Center

Publications and helpful links

General Publications

• Nimri R, Lebenthal Y, Shalitin S, Benzaquen H, Demol S, Phillip M. Metabolic control by insulin detemir in basal-bolus therapy: treat-to-target study in children and adolescents with type 1 diabetes. Pediatr Diabetes. 2013 May;14(3):196-202. doi: 10.1111/pedi.12012. Epub 2013 Jan 4.

Study record dates

Study Major Dates

• Study Start: November 1, 2007
• Primary Completion (Actual): January 1, 2010
• Study Completion (Actual): March 1, 2010

Study Registration Dates

• First Submitted: October 10, 2007
• First Submitted That Met QC Criteria: October 10, 2007
• First Posted (Estimate): October 11, 2007

Study Record Updates

• Last Update Posted (Estimate): November 2, 2011
• Last Update Submitted That Met QC Criteria: November 1, 2011
• Last Verified: July 1, 2010

More Information

Terms related to this study

• Keywords: type 1 diabetes; levemir
• 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 Detemir
• Other Study ID Numbers: rmc004543ctil