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

This study has been terminated.
(See detailed description)
Sponsor:
Information provided by:
Novo Nordisk A/S
ClinicalTrials.gov Identifier:
NCT00509925
First received: July 31, 2007
Last updated: June 26, 2012
Last verified: June 2012
  Purpose

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.


Condition Intervention Phase
Diabetes
Diabetes Mellitus, Type 1
Drug: insulin detemir
Drug: insulin NPH
Drug: insulin aspart
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Crossover Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Effect of Insulin Detemir Compared to Insulin NPH Combined With Insulin Aspart on Energy Expenditure in Subjects With Type 1 Diabetes

Resource links provided by NLM:


Further study details as provided by Novo Nordisk A/S:

Primary Outcome Measures:
  • Total Energy Expenditure, Double-labelled Water Method [ Time Frame: Weeks 14-16, weeks 30-32 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Weeks 14-16, weeks 30-32 ] [ Designated as safety issue: No ]
    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) [ Time Frame: Week 14, week 30 ] [ Designated as safety issue: No ]
    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) [ Time Frame: Week 14, week 30 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Week 16, week 32 ] [ Designated as safety issue: No ]
    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) [ Time Frame: Week 16, week 32 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Week 16, week 32 ] [ Designated as safety issue: No ]
    Body weight after each treatment period.

  • Lean Body Mass [ Time Frame: Week 16, week 32 ] [ Designated as safety issue: No ]
    Lean body mass was measured using Bioelectrical Impedance Analysis (BIA), a method used for estimating body composition.

  • Fat Mass [ Time Frame: Week 16, week 32 ] [ Designated as safety issue: No ]
    Fat mass was measured using Bioelectrical Impedance Analysis (BIA), a method used for estimating body composition.

  • Waist:Hip Ratio [ Time Frame: Week 16, week 32 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Week 14, week 30 ] [ Designated as safety issue: No ]
    Adiponectin levels after each treatment period.

  • Hormonal Assessment: Insulin-like Growth Factor-1 [ Time Frame: Week 14, week 30 ] [ Designated as safety issue: No ]
    Insulin-like growth factor-1 (IGF-1) levels after each treatment period.

  • Hormonal Assessment: Resistin [ Time Frame: Week 14, week 30 ] [ Designated as safety issue: No ]
    Resistin levels after each treatment period.

  • Hormonal Assessment: Leptin [ Time Frame: Week 14, week 30 ] [ Designated as safety issue: No ]
    Leptin levels after each treatment period.

  • Glycosylated Haemoglobin A1c (HbA1c) [ Time Frame: Week 16, week 32 ] [ Designated as safety issue: No ]
    Glycosylated haemoglobin A1c (HbA1c) after each treatment period.

  • Fasting Plasma Glucose [ Time Frame: Week 16, week 32 ] [ Designated as safety issue: No ]
    Fasting plasma glucose (FPG) after each treatment period.

  • Hypoglycaemic Episodes [ Time Frame: Weeks 0-32 ] [ Designated as safety issue: Yes ]
    Total number of hypoglycaemic episodes experienced in the study.

  • Hypoglycaemic Episodes, Diurnal/Nocturnal [ Time Frame: Weeks 0-32 ] [ Designated as safety issue: Yes ]
    Total number of hypoglycaemic episodes during the day (diurnal) and the night (nocturnal) experienced in the study.


Enrollment: 23
Study Start Date: July 2007
Study Completion Date: July 2008
Primary Completion Date: July 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment period 1
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
Drug: insulin detemir
Treat-to-target dose tritation (dose adjusted individually), s.c. (under the skin) injection
Drug: insulin NPH
Treat-to-target dose tritation (dose adjusted individually), s.c. (under the skin) injection
Drug: insulin aspart
Treat-to-target dose tritation (dose adjusted individually), s.c. (under the skin) injection
Experimental: Treatment period 2
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
Drug: insulin detemir
Treat-to-target dose tritation (dose adjusted individually), s.c. (under the skin) injection
Drug: insulin NPH
Treat-to-target dose tritation (dose adjusted individually), s.c. (under the skin) injection
Drug: insulin aspart
Treat-to-target dose tritation (dose adjusted individually), s.c. (under the skin) injection

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

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00509925

Locations
United Kingdom
Guildford, United Kingdom, GU2 7XX
Sponsors and Collaborators
Novo Nordisk A/S
Investigators
Study Director: Nerys John, MD Novo Nordisk Ltd.
  More Information

Additional Information:
No publications provided by Novo Nordisk A/S

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Public Access to Clinical Trials, Novo Nordisk A/S
ClinicalTrials.gov Identifier: NCT00509925     History of Changes
Other Study ID Numbers: NN304-1761, 2006-003060-59
Study First Received: July 31, 2007
Results First Received: April 19, 2010
Last Updated: June 26, 2012
Health Authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 1
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Autoimmune Diseases
Immune System Diseases
Insulin aspart
Insulin
Insulin, NPH
Insulin, Long-Acting
Hypoglycemic Agents
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on July 22, 2014