A prospective, single center, double blind, placebo controlled study of adipocytokines, adipose tissue gene expression and hepatic insulin clearance in the therapeutic response to vildagliptin in ma
- Conditions
- This is a single center, randomized, double-blind pilot study on patients with Type 2 diabetes. The purpose of this study is to test the effects of vildagliptin (as add-on to metformin) on hepatic insulin clearance, on levels of adipocytokines, metabolic syndrome biomarkers and adipose tissue mRNA expression.
- Registration Number
- EUCTR2007-003370-26-DE
- Lead Sponsor
- Charite Universitätsmedizin Berlin
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- All
- Target Recruitment
- Not specified
1.Male, non-fertile female or female of childbearing potential using a medically approved birth control method (Pearl Index < 1).
•A non-fertile female is defined as: post menopausal (12 months of natural (spontaneous) amenorrhea or 6 months of spontaneous amenorrhea with serum FSH levels >40 mIU/m); 6 weeks post bilateral oophorectomy with or without hysterectomy; post hysterectomy; or sterilized by tubal ligation.
•A female of childbearing potential is defined as any woman physiologically capable of becoming pregnant, including women whose career, lifestyle, or sexual orientation precludes intercourse with a male partner and women whose partners have been sterilized by vasectomy or other means.
•Medically approved birth control method (Pearl index<1) include: hormonal contraceptives, IUD, and double-barrier contraception. Acceptable methods of contraception may include total abstinence at the discretion of the investigator in cases where the age, career, lifestyle, or sexual orientation of the subject ensures compliance. Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception.
•Reliable contraception should be maintained throughout the study.
2.Age in the range of 18-78 years inclusive.
3.Patients with T2DM who have taken metformin prior to visit 1.
4.Diagnosis of T2DM for at least 4 weeks prior to study entry (Visit 1).
5.HbA1c <9% inclusive at visit 1.
6.Written informed consent to participate in the study.
7.Ability to comply with all study requirements.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range
1.Pregnant or lactating female or female of childbearing potential without a medically approved birth control method (Pearl Index < 1).
2.A history of:
•type 1 diabetes, diabetes that is a result of pancreatic injury, or secondary forms of diabetes, e.g., Cushing’s syndrome and acromegaly.
•acute metabolic diabetic complications such as ketoacidosis or hyperosmolar state (coma) within the past 6 months.
3.Evidence of significant diabetic complications, e.g., symptomatic autonomic neuropathy or gastroparesis.
4.Acute infections which may affect blood glucose control within 4 weeks prior to visit 1 and other concurrent medical condition that may interfere with the interpretation of efficacy and safety data during the study.
5.Any of the following within the past 6 months:
•myocardial infarction (MI) (if the visit 1 ECG reveals patterns consistent with a MI and the date of the event cannot be determined, then the patient can enter the study at the discretion of the investigator and the sponsor);
•coronary artery bypass surgery or percutaneous coronary intervention;
•unstable angina or stroke.
6.Congestive heart failure (CHF) requiring pharmacological treatment.
7.Any of the following ECG abnormalities:
•Torsades de pointes, sustained and clinically relevant ventricular tachycardia or ventricular fibrillation
•second degree AV block (Mobitz 1 and 2)
•third degree AV block
•prolonged QTc (> 500 msec)
8.Malignancy including leukemia and lymphoma (not including basal cell skin cancer) within the last 5 years.
9.Liver disease such as cirrhosis or chronic active hepatitis.
10.Chronic insulin treatment (> 4 weeks of treatment in the absence of an intercurrent illness) within the past 6 month.
11.Chronic oral or parenteral corticosteroid treatment (> 7 consecutive days of treatment) within 8 weeks prior to visit 1.
12.Treatment with growth hormone or similar drugs.
13.Treatment with class Ia, Ib and Ic or III anti-arrhythmics.
14.Use of other investigational drugs at visit 1, or within 60 days prior to visit 1.
15.Treatment with cytostatic drugs within the past 3 months.
16.History of active substance abuse (including alcohol) within the past 2 years.
17.Any of the following significant laboratory abnormalities:
•ALT, AST greater 2 times the upper limit of the normal range (ULN) at visit 1, confirmed by a repeat measure within 3 working days.
•Total bilirubin greater than 2 times ULN and direct bilirubin greater the upper limit of the normal range at visit 1, confirmed by a repeat measure within 3 working days.
•At any time during the clinical trial, if ALT and/or AST is greater than or equal to 3 times the ULN without clinical symptoms, the tests must be repeated within 3 days. If confirmed the patient must be discontinued.
•At any time during the clinical trial, if ALT and/or AST is greater than or equal to 3 times the ULN, with total bilirubin elevated above the ULN, then the patient must be discontinued immediately
•Clinically significant renal dysfunction as indicated by serum creatinine levels = 1.5 mg/dL (132 ?mol/L) males, = 1.4 mg/dL (123 ?mol/L) females, or a history of abnormal creatinine clearance.
•Clinically significant TSH values outside of normal range at visit 1.
•Clinically significant laboratory abnormalities, confirmed by repeat measurement, other than hyperglycemia, hyperinsulinemia, and glycosuria at visit 1A.
•Fasting triglycerides ? 700 mg/dL (7.9 mmol/L) at visit 1.
18.Lack cooperat
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: The primary objective of this study is to examine the effects of vildagliptin 50mg twice daily used in combination with metformin in patients with type 2 diabetes on the change of Adiponectin level.;Secondary Objective: The changes in hepatic insulin clearance after 12 weeks of treatment will be examined. The changes in the levels of circulating HMW adiponectin and inflammatory and metabolic synrome biomarkers such as CRP, IL1ß and MCP1 will be measured. Furthermore adipose tissue mRNA expression of GIP induced genes including adiponectin receptors and GIP receptors will be studied. GIP regulated genes have been recently identified by our group after infusion of GIP. The most prominently genes will be treated as GIP marker genes.<br>The efficacy of vildagliptin 50 mg twice daily used in combination with metformin to improve glycemic control will be demonstrated by measurement of HbA1c and fasting plasma glucose.<br>;Primary end point(s): change in Adiponectin level
- Secondary Outcome Measures
Name Time Method