Effect of Insulin Detemir on Use of Energy in Type 1 Diabetes

Phase 4

Terminated

Conditions: Diabetes
Diabetes Mellitus, Type 1

Interventions: Drug: insulin detemir
Drug: insulin NPH
Drug: insulin aspart

Registration Number: NCT00509925

Lead Sponsor: Novo Nordisk A/S

Brief Summary: This trial is conducted in Europe. The purpose of this trial is to investigate if there is any change in the mechanism of energy expenditure (i.e. the way in which energy is used) in patients with type 1 diabetes, whilst taking two different, commercially available insulins for the treatment of their diabetes.

Detailed Description: The study had been temporarily halted due to an unplanned interim analysis. The Sponsor is now aware that a further interim analysis has been performed by the site and therefore a decision has been made not to recommence the study

Recruitment & Eligibility

Status: TERMINATED

Sex: All

Target Recruitment: 23

Inclusion Criteria

Type 1 diabetes for more than 12 months
Current treatment: Basal-bolus insulin regimen for more than three months (i.e. at least one daily injection of long-acting insulin (including insulin glargine) and fast-acting insulin with each main meal)
HbA1c (glycosylated haemoglobin A1c) between 7.0 and 11.0%
Able and willing to maintain consistent physical activity level throughout the entire study period
Able and willing to maintain consistent eating habits throughout the entire study period

Exclusion Criteria

Proliferative retinopathy that has required acute treatment within the last six months
Recurrent major hypoglycaemia or hypoglycaemic unawareness as judged by the Investigator
Liver, kidney or heart problems as judged by the Investigator
Pregnancy, breast-feeding, the intention of becoming pregnant or not using adequate contraceptive measures
Known or suspected allergy to trial products or related products
Receipt of any investigational drug within one month prior to this trial

Study & Design

Study Type: INTERVENTIONAL

Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Treatment period 1	insulin NPH	Insulin detemir for 16 weeks (treatment period 1) followed by insulin NPH treatment for 16 weeks (treatment period 2) in addition to meal-time insulin aspart
Treatment period 2	insulin detemir	Insulin NPH for 16 weeks (treatment period 1) followed by insulin detemir treatment for 16 weeks (treatment period 2) in addition to meal-time insulin aspart
Treatment period 2	insulin NPH	Insulin NPH for 16 weeks (treatment period 1) followed by insulin detemir treatment for 16 weeks (treatment period 2) in addition to meal-time insulin aspart
Treatment period 1	insulin detemir	Insulin detemir for 16 weeks (treatment period 1) followed by insulin NPH treatment for 16 weeks (treatment period 2) in addition to meal-time insulin aspart
Treatment period 1	insulin aspart	Insulin detemir for 16 weeks (treatment period 1) followed by insulin NPH treatment for 16 weeks (treatment period 2) in addition to meal-time insulin aspart
Treatment period 2	insulin aspart	Insulin NPH for 16 weeks (treatment period 1) followed by insulin detemir treatment for 16 weeks (treatment period 2) in addition to meal-time insulin aspart

Primary Outcome Measures

Name	Time	Method
Total Energy Expenditure, Dietary Record Method	Weeks 14-16, weeks 30-32	The total energy expenditure (TEE) measured after each treatment period by the dietary record method. The calculation of energy balance is accomplished by compiling an accurate record of food intake over a period of time and measuring any changes in body weight that occur during that time. Data from the 7-day food diary was used to calculate TEE.
Total Energy Expenditure, Double-labelled Water Method	Weeks 14-16, weeks 30-32	Total energy expenditure (TEE) measured after each treatment period by the double-labelled water (DLW) method. This technique required subjects to label their body water using oral administration of water labelled with 2 stable isotopes (2H218O). The clearance of 2H and 18O was measured over a two week period with daily collections of urine. The difference between the clearance of 2H and 18O is a measure of CO2 production rate. This can be converted to provide a measure of energy expenditure.

Secondary Outcome Measures

Name	Time	Method
Component of Total Energy Expenditure: Physical Activity Thermogenesis	Week 16, week 32	Physical activity thermogenesis is a component of TEE (total energy expenditure). Subjects were asked not to change their physical activity levels. Physical activity thermogenesis can be calculated as the difference between TEE minus (REE + DIT), as long as volitional exercise is unchanged. Volitional exercise was assessed using Actiheart 3-D monitor readings. Subjects were asked to measure their normal activity for between 1 and 5 days prior to their visits at week 16 and week 32).
Body Weight	Week 16, week 32	Body weight after each treatment period.
Component of Total Energy Expenditure: Resting Energy Expenditure (REE)	Week 14, week 30	Resting energy expenditure (REE) is a component of TEE (total energy expenditure). It was measured at 2 different timepoints during the trial using indirect calorimetry (measurement of O2 consumption/CO2 production) after an overnight fast when subjects would be metabolising a mixture of carbohydrate and free fatty acid. This technique allowed the calculation of the rate of carbohydrate and lipid oxidation.
Component of Total Energy Expenditure: Diet Induced Thermogenesis (DIT)	Week 14, week 30	Diet induced thermogenesis (DIT) is a component of TEE (total energy expenditure) and is the energy expenditure following feeding for anabolic processes. Subjects fasted overnight and rested for 1 hour. Multiple measurements of REE (resting energy expenditure) were taken. A fixed 600 kcal liquid meal was given and REE was measured over the next 3 hours. DIT was calculated as area under the curve of total REE-resting REE for the 3-hour period and was then converted to a per day measurement by taking into account each individual's average daily food intake.
Component of Total Energy Expenditure: Non-exercise Activity Thermogenesis (NEAT)	Week 16, week 32	Non-exercise activity thermogenesis is a component of TEE (total energy expenditure). Thermic efficiency was assessed by measuring O2 consumption/CO2 production while the subject exercised on a bike for 20 minutes while hooked up to a device that recorded their respiration (visit in week 14 and week 30). If thermic efficiency was unchanged and volitional exercise was unchanged, then any change in physical activity thermogenesis was due to changes in NEAT.
Lean Body Mass	Week 16, week 32	Lean body mass was measured using Bioelectrical Impedance Analysis (BIA), a method used for estimating body composition.
Waist:Hip Ratio	Week 16, week 32	At each time-point, 3 measurements each of waist and hip circumference were taken, then an average across the three measurements was calculated for both and the ratio was calculated as the waist average in cm divided by hip average in cm, and multiplied by 100.
Glycosylated Haemoglobin A1c (HbA1c)	Week 16, week 32	Glycosylated haemoglobin A1c (HbA1c) after each treatment period.
Fasting Plasma Glucose	Week 16, week 32	Fasting plasma glucose (FPG) after each treatment period.
Hypoglycaemic Episodes	Weeks 0-32	Total number of hypoglycaemic episodes experienced in the study.
Fat Mass	Week 16, week 32	Fat mass was measured using Bioelectrical Impedance Analysis (BIA), a method used for estimating body composition.
Hormonal Assessment: Adiponectin	Week 14, week 30	Adiponectin levels after each treatment period.
Hormonal Assessment: Insulin-like Growth Factor-1	Week 14, week 30	Insulin-like growth factor-1 (IGF-1) levels after each treatment period.
Hormonal Assessment: Resistin	Week 14, week 30	Resistin levels after each treatment period.
Hormonal Assessment: Leptin	Week 14, week 30	Leptin levels after each treatment period.
Hypoglycaemic Episodes, Diurnal/Nocturnal	Weeks 0-32	Total number of hypoglycaemic episodes during the day (diurnal) and the night (nocturnal) experienced in the study.