Comparison of the Change in Fat Distribution in Overweight and Obese Subjects With Type 2 Diabetes After Insulin Treatment

• ClinicalTrials.gov Identifier: NCT00795600
• Recruitment Status: Completed
• First Posted: November 21, 2008
• Results First Posted: June 17, 2013
• Last Update Posted: March 16, 2016
• Sponsor: Novo Nordisk A/S
• Information provided by (Responsible Party): Novo Nordisk A/S

Study Description

Brief Summary:

This trial is conducted in Europe. The aim of this clinical trial is to compare the change in trunk fat mass, assessed by Double Energy X-ray Absorptiometry (DEXA) after 26 weeks of treatment with insulin detemir or insulin NPH (Neutral Protamine Hagedorn) (both combined with insulin aspart at the main meals) in overweight and obese subjects with type 2 diabetes.

Condition or disease	Intervention/treatment	Phase
Diabetes; Diabetes Mellitus, Type 2	Drug: insulin detemir; Drug: insulin NPH	Phase 4

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 60 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Multi-centre, Open-labelled, Randomised, Two-group Parallel Trial Comparing the Change in Fat Distribution in Overweight and Obese Subjects With Type 2 Diabetes After 26 Weeks of Treatment With Insulin Detemir Once Daily Versus Insulin NPH Once Daily, Both With Insulin Aspart at Mealtimes
• Study Start Date: April 2009
• Actual Primary Completion Date: August 2010
• Actual Study Completion Date: August 2010

Arms and Interventions

Arm	Intervention/treatment
Experimental: insulin detemir; Insulin detemir injected subcutaneously (s.c.) in the evening in combination with insulin aspart injected s.c. as mealtime insulin for 26 weeks	Drug: insulin detemir; Insulin detemir once daily plus insulin aspart at mealtime
Active Comparator: insulin NPH; Insulin isophane (Neutral Protamine Hagedorn, NPH) injected subcutaneously (s.c.) in the evening in combination with insulin aspart injected s.c. as mealtime insulin for 26 weeks	Drug: insulin NPH; Insulin NPH once daily plus insulin aspart at mealtime

Outcome Measures

Primary Outcome Measures :

1. Percentage Change in Trunk Fat Mass (Defined as Peripheral Fat Ratio) [ Time Frame: week 0, week 26 ]
   Percentage of change of trunk fat mass as the dependent variable, baseline value (trunk fat mass at week 0) as covariate, treatment with metformin (yes/no) and gender (male/female) as effect and the treatment received (insulin detemir/insulin NPH) as the main factor.
2. Absolute Change in Trunk Fat Mass [ Time Frame: week 0, week 26 ]
   Absolute change in trunk fat mass as response variable with treatment, sex and Metformin use as fixed factors, and trunk fat mass at week 0 as covariate.

Secondary Outcome Measures :

1. Absolute Change in Whole Body Fat Mass [ Time Frame: Week 0, week 26 ]
   Absolute change in whole body fat mass as response variable with treatment, sex and Metformin use as fixed factors, and trunk fat mass at week 0 as covariate.
2. Percentage Change in Whole Body Fat Mass [ Time Frame: Week 0, week 26 ]
   Percentage Change in Whole Body Fat Mass as response variable with treatment, sex and Metformin use as fixed factors, and whole Body Fat Mass at week 0 as covariate.
3. Absolute Change in Whole Body Lean Mass [ Time Frame: Week 0, week 26 ]
   Absolute change in whole body lean mass as response variable with treatment, sex and Metformin use as fixed factors, whole body lean mass at week 0 as covariate.
4. Percentage Change in Whole Body Lean Mass [ Time Frame: Week 0, week 26 ]
   Percentage Change in Whole Body Lean Mass as response variable with treatment, sex and Metformin use as fixed factors, and whole Body Lean Mass at week 0 as covariate.
5. Absolute Change in Trunk Lean Mass [ Time Frame: Week 0, week 26 ]
   Absolute change in trunk lean mass as response variable with treatment, sex and Metformin use as fixed factors, and trunk lean mass at week 0 as covariate
6. Percentage Change in Trunk Lean Mass [ Time Frame: Week 0, week 26 ]
   Percentage Change in Trunk Lean Mass as response variable with treatment, sex and Metformin use as fixed factors, and Trunk Lean Mass at week 0 as covariate.
7. Absolute Change in Calculated Whole Body Fat Percentage [ Time Frame: Week 0, week 26 ]
   Absolute change in calculated whole body fat percentage as response variable with treatment, sex and Metformin use as fixed factors, and calculated whole body fat percentage at week 0 as covariate
8. Percentual Change in Calculated Whole Body Fat Percentage [ Time Frame: Week 0, week 26 ]
   Percentual Change in Calculated Whole Body Fat Percentage as response variable with treatment, sex and Metformin use as fixed factors, and Calculated Whole Body Fat Percentage at week 0 as covariate.
9. Absolute Change in Calculated Trunk Fat Percentage [ Time Frame: Week 0, week 26 ]
   Absolute change in calculated trunk fat percentage as response variable with treatment, sex and Metformin use as fixed factors, and calculated trunk fat percentage at week 0 as covariate
10. Percentual Change in Calculated Trunk Fat Percentage [ Time Frame: Week 0, week 26 ]
    Percentual Change in Calculated Trunk Fat Percentage as response variable with treatment, sex and Metformin use as fixed factors, and Calculated Trunk Fat Percentage at week 0 as covariate.
11. Absolute Change in Visceral Adipose Tissue Area [ Time Frame: Week 0, week 26 ]
    Absolute change in visceral adipose tissue area as response variable with treatment, sex and Metformin use as fixed factors, and visceral adipose tissue area at week 0 as covariate
12. Percentage Change in Visceral Adipose Tissue Area [ Time Frame: Week 0, week 26 ]
    Percentage Change in Visceral Adipose Tissue Area as response variable with treatment, sex and Metformin use as fixed factors, and Visceral Adipose Tissue Area at week 0 as covariate.
13. Absolute Change in Subcutaneous Adipose Tissue Area [ Time Frame: Week 0, week 26 ]
    Absolute change in subcutaneous adipose tissue area as response variable with treatment, sex and Metformin use as fixed factors, and subcutaneous adipose tissue area at week 0 as covariate
14. Percentage Change in Subcutaneous Adipose Tissue Area [ Time Frame: Week 0, week 26 ]
    Percentage Change in Subcutaneous Adipose Tissue Area as response variable with treatment, sex and Metformin use as fixed factors, and Subcutaneous Adipose Tissue Area at week 0 as covariate.
15. Absolute Change in Calculated Visceral/Subcutaneous Adipose Tissue Ratio [ Time Frame: Week 0, week 26 ]
    Absolute change in Calculated Visceral/Subcutaneous Adipose Tissue Ratio as response variable with treatment, sex and Metformin use as fixed factors, and Calculated Visceral/Subcutaneous Adipose Tissue Area at week 0 as covariate.
16. Percentage Change in Calculated Visceral/Subcutaneous Adipose Tissue Ratio [ Time Frame: Week 0, week 26 ]
    Percentage Change in Calculated Visceral/Subcutaneous Adipose Tissue Area as response variable with treatment, sex and Metformin use as fixed factors, and Calculated Visceral/Subcutaneous Adipose Tissue Area at week 0 as covariate.
17. Absolute Change in Liver/Spleen Attenuation Ratio [ Time Frame: Week 0, week 26 ]
    Absolute change in Liver/Spleen Attenuation Ratio as response variable with treatment, sex and Metformin use as fixed factors, and Liver/Spleen Attenuation Ratio at week 0 as covariate.
18. Percentage Change in Liver/Spleen Attenuation Ratio [ Time Frame: Week 0, week 26 ]
    Percentage Change in Liver/Spleen Attenuation Ratio as response variable with treatment, sex and Metformin use as fixed factors, and Liver to Spleen Attenuation Ratio at week 0 as covariate.
19. Absolute Change in HbA1c (Glycosylated Haemoglobin) [ Time Frame: Week 0, week 26 ]
    Absolute Change in HbA1c as response variable with treatment, sex and Metformin use as fixed factors, and HbA1c at week 0 as covariate.
20. Absolute Change in Fasting Plasma Glucose (FPG) [ Time Frame: Week 0, week 26 ]
    Absolute Change in Fasting Plasma Glucose as response variable with treatment, sex and Metformin use as fixed factors, and Fasting Plasma Glucose at week 0 as covariate.
21. Absolute Change in Adiponectin [ Time Frame: Week 0, week 26 ]
    Absolute change in adiponectin as response variable with treatment, sex and Metformin use as fixed factors, and Adiponectic at week 0 as covariate.
22. Absolute Change in Total Cholesterol [ Time Frame: Week 0, week 26 ]
23. Absolute Change in High Density Lipoprotein (HDL) Cholesterol [ Time Frame: Week 0, week 26 ]
24. Absolute Change in Low Density Lipoprotein (LDL) Cholesterol [ Time Frame: Week 0, week 26 ]
25. Absolute Change in Very Low Density Lipoprotein (VLDL) Cholesterol [ Time Frame: Week 0, week 26 ]
26. Absolute Change in Triglycerides [ Time Frame: Week 0, week 26 ]
27. Absolute Change in Free Fatty Acids [ Time Frame: Week 0, week 26 ]
28. Absolute Change in Haemoglobin [ Time Frame: Week 0, week 26 ]
29. Absolute Change in Blood Volume (Haematocrit) [ Time Frame: Week 0, week 26 ]
30. Absolute Change in Thrombocytes [ Time Frame: Week 0, week 26 ]
31. Absolute Change in Erythrocytes [ Time Frame: Week 0, week 26 ]
32. Absolute Change in Leucocytes [ Time Frame: Week 0, week 26 ]
33. Absolute Change in Lymphocytes [ Time Frame: Week 0, week 26 ]
34. Absolute Change in Monocytes [ Time Frame: Week 0, week 26 ]
35. Absolute Change in Neutrophils [ Time Frame: Week 0, week 26 ]
36. Absolute Change in Eosinophils [ Time Frame: Week 0, week 26 ]
37. Absolute Change in Basophils [ Time Frame: Week 0, week 26 ]
38. Absolute Change in Creatinine [ Time Frame: Week 0, week 26 ]
39. Absolute Change in Creatine Phosphokinase [ Time Frame: Week 0, week 26 ]
40. Absolute Change in Urea [ Time Frame: Week 0, week 26 ]
41. Absolute Change in Albumin [ Time Frame: Week 0, week 26 ]
42. Absolute Change in Bilirubin Total [ Time Frame: Week 0, week 26 ]
43. Absolute Change in Alanine Aminotransferase (ALAT) [ Time Frame: Week 0, week 26 ]
44. Absolute Change in Aspartate Aminotransferase (ASAT) [ Time Frame: Week 0, week 26 ]
45. Absolute Change in Alkaline Phosphatase [ Time Frame: Week 0, week 26 ]
46. Absolute Change in Sodium [ Time Frame: Week 0, week 26 ]
47. Absolute Change in Potassium [ Time Frame: Week 0, week 26 ]
48. Absolute Change in Body Weight [ Time Frame: Week 0, week 26 ]
    Absolute change in body weight was based on ANCOVA model for absolute change from week 0 to week 26 as response variable with treatment, sex and Metformin use as fixed factors, and body weight at week 0 as covariable.
49. Absolute Change in Waist Circumference [ Time Frame: Week 0, week 26 ]
    Absolute change in waist circumference was based on ANCOVA model for absolute change from week 0 to week 26 as response variable with treatment, sex and Metformin use as fixed factors, and Waist at week 0 as covariate.
50. Absolute Change in Hip Circumference [ Time Frame: Week 0, week 26 ]
    Absolute Change in Hip Circumferences was based on ANCOVA model for absolute change from week 0 to week 26 as response variable with treatment, sex, and Metformin use as fixed factors, and hip circumference at week 0 as covariate.
51. Absolute Change in hsCRP (Highly Sensitive C Reactive Protein) [ Time Frame: Week 0, week 26 ]
    Absolute change in hsCRP was based on ANCOVA model for absolute change from week 0 to week 26 as response variable with treatment, sex and Metformin use as fixed factors, and hsCRP at week 0 as covariate.
52. Absolute Change in PAI-1 (Plasminogen Activator Inhibitor-1) [ Time Frame: Week 0, week 26 ]
53. Number of Hypoglycaemic Episodes [ Time Frame: Weeks 0-26 ]
    Number of episodes reported during the trial.
54. Number of Non-serious Adverse Events [ Time Frame: Weeks 0-26 ]
    Number of episodes reported during the trial.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Subjects with type 2 diabetes who have been treated with 2 or 3 doses of insulin (one of them must be a premix) for at least 3 months prior to inclusion in trial
• Glycosylated haemoglobin (HbA1c) between 7.0-11.0 %
• Body Mass Index (BMI) between 27.5-40 kg/m^2

Exclusion Criteria:

• Treatment with any oral antidiabetic drugs (OADs) in the last 6 months except metformin (subjects currently treated with metformin within the interval of 1000 - 2550 mg daily may be included in the trial. The dose should have remained unchanged for a period of 2 months prior to randomisation and should be expected to remain unchanged throughout the trial period)
• Use of approved weight lowering pharmacotherapy (e.g. orlistat, sibutramin, rimonabant) or obesity induced by drug treatment (e.g. corticosteroids, Non-steroidal anti-inflammatory drugs (NSAIDs), tricyclic anti-depressants, atypical anti-psychotics)
• Previous or planned surgical treatment of obesity
• Total daily insulin dose higher or equal 2 IU/kg
• Proliferative retinopathy or maculopathy that has required acute treatment within the last six months
• Receipt of any investigational drug within 1 month prior to this trial
• Cardiac disease defined according to New York Heart Association (NYHA) class III or IV, unstable angina pectoris and/or myocardial infarction within the last 6 months previous to the selection

Contacts and Locations

Locations

Spain

Málaga, Spain, 29009

Sponsors and Collaborators

Novo Nordisk A/S

Investigators

• Study Director: Global Clinical Registry (GCR, 1452); Novo Nordisk A/S

More Information

Additional Information:

Clinical Trials at Novo Nordisk 

• Responsible Party: Novo Nordisk A/S
• ClinicalTrials.gov Identifier: NCT00795600 History of Changes
• Other Study ID Numbers: NN304-3614; 2008-003739-19 ( EudraCT Number )
• First Posted: November 21, 2008
• Results First Posted: June 17, 2013
• Last Update Posted: March 16, 2016
• Last Verified: February 2016

Additional relevant MeSH terms:

Diabetes Mellitus; Diabetes Mellitus, Type 2; Overweight; Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Body Weight; Signs and Symptoms; Insulin; Insulin, Globin Zinc; Insulin Aspart; Insulin, Long-Acting; Insulin degludec, insulin aspart drug combination; Insulin Detemir; Isophane Insulin, Human; Insulin, Isophane; Isophane insulin, beef; Hypoglycemic Agents; Physiological Effects of Drugs