Back to resultsEffect of Insulin Detemir on Use of Energy in Type 1 Diabetes
Primary Purpose
Diabetes, Diabetes Mellitus, Type 1
Status
Terminated
Phase
Phase 4
Locations
United Kingdom
Study Type
Interventional
Intervention
insulin detemir
insulin NPH
insulin aspart
Sponsored by
About this trial
This is an interventional treatment trial for Diabetes
Eligibility Criteria
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
Sites / Locations
- Novo Nordisk Investigational Site
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
Treatment period 1
Treatment period 2
Arm Description
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
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
Outcomes
Primary Outcome Measures
Total Energy Expenditure, Double-labelled Water Method
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.
Total Energy Expenditure, Dietary Record Method
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.
Secondary Outcome Measures
Component of Total Energy Expenditure: Resting Energy Expenditure (REE)
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)
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: Physical Activity Thermogenesis
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).
Component of Total Energy Expenditure: Non-exercise Activity Thermogenesis (NEAT)
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.
Body Weight
Body weight after each treatment period.
Lean Body Mass
Lean body mass was measured using Bioelectrical Impedance Analysis (BIA), a method used for estimating body composition.
Fat Mass
Fat mass was measured using Bioelectrical Impedance Analysis (BIA), a method used for estimating body composition.
Waist:Hip Ratio
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.
Hormonal Assessment: Adiponectin
Adiponectin levels after each treatment period.
Hormonal Assessment: Insulin-like Growth Factor-1
Insulin-like growth factor-1 (IGF-1) levels after each treatment period.
Hormonal Assessment: Resistin
Resistin levels after each treatment period.
Hormonal Assessment: Leptin
Leptin levels after each treatment period.
Glycosylated Haemoglobin A1c (HbA1c)
Glycosylated haemoglobin A1c (HbA1c) after each treatment period.
Fasting Plasma Glucose
Fasting plasma glucose (FPG) after each treatment period.
Hypoglycaemic Episodes
Total number of hypoglycaemic episodes experienced in the study.
Hypoglycaemic Episodes, Diurnal/Nocturnal
Total number of hypoglycaemic episodes during the day (diurnal) and the night (nocturnal) experienced in the study.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT00509925
Brief Title
Effect of Insulin Detemir on Use of Energy in Type 1 Diabetes
Official Title
A 32-week National, Single-centre, Open-labelled, Randomised, Crossover Trial Comparing Energy Expenditure With Insulin Detemir Versus NPH Insulin Using a Basal-Bolus Regimen With Insulin Aspart as Mealtime Insulin in Subjects With Type 1 Diabetes
Study Type
Interventional
2. Study Status
Record Verification Date
January 2017
Overall Recruitment Status
Terminated
Why Stopped
See detailed description
Study Start Date
July 2007 (undefined)
Primary Completion Date
July 2008 (Actual)
Study Completion Date
July 2008 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Novo Nordisk A/S
4. Oversight
Data Monitoring Committee
No
5. Study Description
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
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Diabetes, Diabetes Mellitus, Type 1
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Crossover Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
23 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Treatment period 1
Arm Type
Experimental
Arm Description
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
Arm Title
Treatment period 2
Arm Type
Experimental
Arm Description
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
Intervention Type
Drug
Intervention Name(s)
insulin detemir
Intervention Description
Treat-to-target dose tritation (dose adjusted individually), s.c. (under the skin) injection
Intervention Type
Drug
Intervention Name(s)
insulin NPH
Intervention Description
Treat-to-target dose tritation (dose adjusted individually), s.c. (under the skin) injection
Intervention Type
Drug
Intervention Name(s)
insulin aspart
Intervention Description
Treat-to-target dose tritation (dose adjusted individually), s.c. (under the skin) injection
Primary Outcome Measure Information:
Title
Total Energy Expenditure, Double-labelled Water Method
Description
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.
Time Frame
Weeks 14-16, weeks 30-32
Title
Total Energy Expenditure, Dietary Record Method
Description
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.
Time Frame
Weeks 14-16, weeks 30-32
Secondary Outcome Measure Information:
Title
Component of Total Energy Expenditure: Resting Energy Expenditure (REE)
Description
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.
Time Frame
Week 14, week 30
Title
Component of Total Energy Expenditure: Diet Induced Thermogenesis (DIT)
Description
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.
Time Frame
Week 14, week 30
Title
Component of Total Energy Expenditure: Physical Activity Thermogenesis
Description
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).
Time Frame
Week 16, week 32
Title
Component of Total Energy Expenditure: Non-exercise Activity Thermogenesis (NEAT)
Description
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.
Time Frame
Week 16, week 32
Title
Body Weight
Description
Body weight after each treatment period.
Time Frame
Week 16, week 32
Title
Lean Body Mass
Description
Lean body mass was measured using Bioelectrical Impedance Analysis (BIA), a method used for estimating body composition.
Time Frame
Week 16, week 32
Title
Fat Mass
Description
Fat mass was measured using Bioelectrical Impedance Analysis (BIA), a method used for estimating body composition.
Time Frame
Week 16, week 32
Title
Waist:Hip Ratio
Description
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.
Time Frame
Week 16, week 32
Title
Hormonal Assessment: Adiponectin
Description
Adiponectin levels after each treatment period.
Time Frame
Week 14, week 30
Title
Hormonal Assessment: Insulin-like Growth Factor-1
Description
Insulin-like growth factor-1 (IGF-1) levels after each treatment period.
Time Frame
Week 14, week 30
Title
Hormonal Assessment: Resistin
Description
Resistin levels after each treatment period.
Time Frame
Week 14, week 30
Title
Hormonal Assessment: Leptin
Description
Leptin levels after each treatment period.
Time Frame
Week 14, week 30
Title
Glycosylated Haemoglobin A1c (HbA1c)
Description
Glycosylated haemoglobin A1c (HbA1c) after each treatment period.
Time Frame
Week 16, week 32
Title
Fasting Plasma Glucose
Description
Fasting plasma glucose (FPG) after each treatment period.
Time Frame
Week 16, week 32
Title
Hypoglycaemic Episodes
Description
Total number of hypoglycaemic episodes experienced in the study.
Time Frame
Weeks 0-32
Title
Hypoglycaemic Episodes, Diurnal/Nocturnal
Description
Total number of hypoglycaemic episodes during the day (diurnal) and the night (nocturnal) experienced in the study.
Time Frame
Weeks 0-32
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Global Clinical Registry (GCR, 1452)
Organizational Affiliation
Novo Nordisk A/S
Official's Role
Study Director
Facility Information:
Facility Name
Novo Nordisk Investigational Site
City
Guildford
ZIP/Postal Code
GU2 7XX
Country
United Kingdom
12. IPD Sharing Statement
Citations:
PubMed Identifier
21593292
Citation
Zachariah S, Sheldon B, Shojaee-Moradie F, Jackson NC, Backhouse K, Johnsen S, Jones RH, Umpleby AM, Russell-Jones DL. Insulin detemir reduces weight gain as a result of reduced food intake in patients with type 1 diabetes. Diabetes Care. 2011 Jul;34(7):1487-91. doi: 10.2337/dc11-0098. Epub 2011 May 18.
Results Reference
result
Links:
URL
http://novonordisk-trials.com
Description
Clinical Trials at Novo Nordisk
Learn more about this trial
Effect of Insulin Detemir on Use of Energy in Type 1 Diabetes
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