Study on Liver Fat Content and Visceral Fat Mass in Overweight and Obese Type 2 Diabetes Patients After Treatment With Basal Insulin

Type 2 Diabetes Mellitus Clinical Trial

Official title:

A Multi-centre, Open-labeled, Randomized, Parallel Study on Liver Fat Content and Visceral Fat Mass in Overweight and Obese Type 2 Diabetes Patients After 26 Weeks Treatment With Insulin Detemir Once Daily Versus Insulin NPH Once Daily

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT01310452
• Other study ID #: prof gao xin
• Status: Active, not recruiting
• Phase: N/A
• First received: March 7, 2011
• Last updated: March 7, 2011
• Start date: January 2011

Study information

• Verified date: June 2010
• Source: Fudan University
• Contact: n/a
• Is FDA regulated: No
• Health authority: China: Ethics Committee
• Study type: Interventional

Clinical Trial Summary

Primary objective:

To compare the change in liver fat content and visceral fat mass (cm2) assessed by MRS (Magnetic Resonance Spectroscopy) and MRI (Magnetic Resonance Image), after 26 weeks of treatment with insulin detemir once daily or insulin NPH once daily both with metformin in overweight and obese type 2 diabetic subjects.

Secondary objectives:

To compare the two treatments with respect to:

1. Efficacy:

• MRI: abdominal subcutaneous fat mass(cm2), Calculated Visceral/Subcutaneous Adipose Tissue Ratio.

• Change in HbA1c from baseline at 12 and 26 weeks of treatment.

• Change in Fasting plasma glucose from baseline at 12 and 26 weeks of treatment.

• Weight

• Waist and hip circumference

2. Safety:

• Incidence of hypoglycaemia in the 26 weeks of treatment with insulin detemir versus NPH

• Lipid profile at the start and after 26 weeks of treatment

• Incidence of Adverse events during the trial

• Safety profile as measured by laboratory safety parameters (haematology, biochemistry) and physical examination/vital signs before and at the end of treatment

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 50
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 70 Years

Eligibility

Inclusion Criteria:

• Informed consent obtained before any trial-related activities. (Trial-related activities are any procedure that would not have been performed during normal management of the subject.)

• Female or male, 18 years=age=70years

• Subjects with insulin naïve type 2 diabetes who have been treated with metformin(>1g/d)alone for at least 3 months prior to screening

• 11%=HbA1c=7.5% based on analysis from a central laboratory

• 24kg/m2=BMI=40kg/m2

• Weight fluctuation<2kg in one month prior to screening

• Able and willing to perform self-monitoring of blood glucose.

• Willing to accept basal insulin therapy

• Able to self-inject all required doses of insulin

Exclusion Criteria:

• Treatment with any OADs (Oral Antidiabetic Drugs) in the last 6 months, except metformin (subjects currently treated with metformin within the interval of 1000-2000 mg daily may be included in the trial. The dose should have remained unchanged for a period of one month prior to randomisation and should be expected to remain unchanged throughout the trial period).

• Use of approved weight lowering pharmacotherapy (e.g. orlistat, sibutramine, rimonabant) or obesity induced by drug treatment (e.g. corticosteroids, NSAIDs, tricyclic anti-depressants, atypical anti-psychotics).

• Participation in a clinical study of weight control within the last 3 months prior to screening.

• Previous or planned surgical treatment of obesity.

• Any disease or condition (such as renal, hepatic or cardiac) according to the judgment of the Investigator makes the subject unsuitable for participation in the trial.

• Anticipated change in concomitant medication known to interfere with glucose metabolism, such as systemic steroids, non-selective beta-blockers or mono amine oxidase (MAO) inhibitors.

• Anticipated change in concomitant medication known to interfere with lipid metabolism, such as lipid-lowering drugs.

• Proliferative retinopathy or maculopathy that has required acute treatment within the last six months.

• Uncontrolled hypertension (treated or untreated) as judged by the Investigator

• Known or suspected allergy to trial product(s) or related products.

• Previous participation in this trial. Participation is defined as screened.

• Pregnant, breast-feeding or the intention of becoming pregnant or not using adequate contraceptive measures. Adequate contraceptive measures are sterilisation, intrauterine device (IUD), oral contraceptives or consistent use of barrier methods.

• Mental incapacity, unwillingness or language barriers precluding adequate understanding or cooperation.

• Any condition that the Investigator feels would interfere with trial participation or evaluation of results.

• Receipt of any investigational drug (NPH or insulin detemir) within 1 month prior to this trial.

• Cardiac disease defined according to NYHA class III or IV, unstable angina pectoris and/or myocardial infarction within the last 6 months previous to the selection.

• History of hypoglycaemic unawareness.

• With mental implant (such as cardiac pacemaker, insulin pump) in vivo.

Study Design

Allocation: Randomized, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Basic Science

Related Conditions & MeSH terms

• Diabetes Mellitus, Type 2
• Type 2 Diabetes Mellitus

Intervention

Drug:
• insulin detemir
insulin detemir once daily with metformin
• neutral protamine insulin
neutral protamine insulin once daily with metformin

Locations

Country	Name	City	State
China	Zhong Shan Hospital, Fudan University	Shang hai

Sponsors (2)

Lead Sponsor	Collaborator
Fudan University	Novo Nordisk A/S

Country where clinical trial is conducted

China, 

References & Publications (9)

Hollander P, Raslova K, Skjøth TV, Råstam J, Liutkus JF. Efficacy and safety of insulin detemir once daily in combination with sitagliptin and metformin: the TRANSITION randomized controlled trial. Diabetes Obes Metab. 2011 Mar;13(3):268-75. doi: 10.1111/j.1463-1326.2010.01351.x. — View Citation

Holman RR, Paul SK, Bethel MA, Matthews DR, Neil HA. 10-year follow-up of intensive glucose control in type 2 diabetes. N Engl J Med. 2008 Oct 9;359(15):1577-89. doi: 10.1056/NEJMoa0806470. Epub 2008 Sep 10. — View Citation

Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). UK Prospective Diabetes Study (UKPDS) Group. Lancet. 1998 Sep 12;352(9131):837-53. Erratum in: Lancet 1999 Aug 14;354(9178):602. — View Citation

Lean ME, Powrie JK, Anderson AS, Garthwaite PH. Obesity, weight loss and prognosis in type 2 diabetes. Diabet Med. 1990 Mar-Apr;7(3):228-33. — View Citation

Mandosi E, Fallarino M, Rossetti M, Gatti A, Morano S. Waist circumference reduction after insulin detemir therapy in type 2 diabetes patients previously treated with NPH. Diabetes Res Clin Pract. 2009 May;84(2):e18-20. doi: 10.1016/j.diabres.2009.02.006. Epub 2009 Mar 17. — View Citation

Mokdad AH, Ford ES, Bowman BA, Nelson DE, Engelgau MM, Vinicor F, Marks JS. Diabetes trends in the U.S.: 1990-1998. Diabetes Care. 2000 Sep;23(9):1278-83. — View Citation

Nathan DM, Buse JB, Davidson MB, Ferrannini E, Holman RR, Sherwin R, Zinman B; American Diabetes Association; European Association for Study of Diabetes. Medical management of hyperglycemia in type 2 diabetes: a consensus algorithm for the initiation and adjustment of therapy: a consensus statement of the American Diabetes Association and the European Association for the Study of Diabetes. Diabetes Care. 2009 Jan;32(1):193-203. doi: 10.2337/dc08-9025. Epub 2008 Oct 22. — View Citation

Philis-Tsimikas A, Charpentier G, Clauson P, Ravn GM, Roberts VL, Thorsteinsson B. Comparison of once-daily insulin detemir with NPH insulin added to a regimen of oral antidiabetic drugs in poorly controlled type 2 diabetes. Clin Ther. 2006 Oct;28(10):1569-81. Erratum in: Clin Ther. 2006 Nov;28(11):1967. — View Citation

Whittingham JL, Havelund S, Jonassen I. Crystal structure of a prolonged-acting insulin with albumin-binding properties. Biochemistry. 1997 Mar 11;36(10):2826-31. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The change in liver fat content and visceral fat mass	To compare the change in liver fat content and visceral fat mass (cm2), assessed by MRS and MRI, after 26 weeks of treatment with insulin detemir or insulin NPH (both with metformin) in overweight and obese type 2 diabetic subjects	After 26 weeks of treatment	No
Secondary	MRI	Abdominal subcutaneous fat mass(cm2), Calculated Visceral/Subcutaneous Adipose Tissue Ratio.	after 26 weeks of treatment	No
Secondary	Change in HbA1c	Change in HbA1c from baseline at 12 and 26 weeks of treatment respectively	from baseline to 12 and 26 weeks of treatment respectively	No
Secondary	Change in Fasting plasma glucose	Change in Fasting plasma glucose (FPG) from baseline at 12 and 26 weeks of treatment respectively	From baseline to 12 and 26 weeks	No
Secondary	Weight at every visit	Weight at every visit	At every visit	No
Secondary	Waist and hip circumference at every visit	Waist and hip circumference at every visit	At every visit	No
Secondary	Hypoglycaemia	Incidence of hypoglycaemia in the 26 weeks of treatment with insulin detemir versus NPH	during the 26-week treatment	Yes
Secondary	Lipid profile	Lipid profile at the start and after 26 weeks of treatment	At the start and after 26 weeks of treatment	Yes
Secondary	Adverse events	Incidence of Adverse events during the trial	During the trial	No
Secondary	Safety profile	Safety profile as measured by laboratory safety parameters (haematology, biochemistry) and physical examination/vital signs before and at the end of treatment	During the treatment	Yes