Clinical trial NCT00542399: Comparing the Metabolic Control of Once to Twice-daily Insulin Detemir Injections
Official title: Comparing the Metabolic Control of Once to Twice-daily Insulin Detemir Injections in Children and Adolescence With Type 1 Diabetes Mellitus.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Type 1 Diabetes Mellitus
Keywords: levemir
type 1 diabetes
Lead sponsor: Rabin Medical Center
Sponsor class: OTHER
First posted: 2007-10-11
Enrollment: 50
Sex: ALL
Minimum age (years): 6
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: HbA1C
timeFrame: at screening visit, at the middle of the study, at the end of the study and prior to sweetching to twice daily treatment
measure: SBGM
timeFrame: 4-8 times a day
measure: CGMS
timeFrame: 72 hours prior to switching to twice daily treatment and at the end of study
measure: Total daily basal and bolus insulin
timeFrame: will be calculated every visit
Secondary outcomes:
measure: documentation of hypoglycemic and hyperglycemic episodes
timeFrame: diary will be collected every visit
Other outcomes:
Locations:
city: Petach-Tikva
country: Israel
facility: Schneider Children's Medical Center
Study officials:
affiliation: Schneider Children Medical Center
name: Moshe Phillip, Professor
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.