"Effect of Dipeptidyl Peptidase IV After Diets in näive Type 2 Diabetic Patients"

This study has been completed.
Sponsor:
Collaborator:
University of Sao Paulo
Information provided by (Responsible Party):
Nanci Valeis, University of Sao Paulo General Hospital
ClinicalTrials.gov Identifier:
NCT00881543
First received: April 14, 2009
Last updated: May 24, 2012
Last verified: May 2012
  Purpose

The purpose of this study is to demonstrate the secretion of glucose, insulin, glucagon, C-peptide and lipid profile after isocaloric diets with different nutritional compounds (fat, protein and carbohydrate food) in drug näive tipo 2 patients.


Condition Intervention
Diabetes Type 2
Drug: Dipeptidyl Peptidase IV inhibitors

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: "Effect of Dipeptidyl Peptidase IV Inhibitors on Glycemia, Insulin, Glucagon, C Peptide, Glp 1 and Lipids After Isocaloric Meals With Different Nutritional Composition in Patients With Type 2 Diabetes näive of Treatment"

Resource links provided by NLM:


Further study details as provided by University of Sao Paulo General Hospital:

Primary Outcome Measures:
  • secretion of glucose, insulin, glucagon, C-peptide and lipid profile after isocaloric diets [ Time Frame: One month ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Washout of dipeptidyl peptidase IV inhibitors after one month without the drug [ Time Frame: One month ] [ Designated as safety issue: No ]

Enrollment: 45
Study Start Date: June 2009
Study Completion Date: October 2011
Primary Completion Date: June 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: 1
This arm will begin taking the placebo by a month, after a month will be tested the diets (the same caloric amount with different composition on fat, protein and carbohydrates)making curves of insulin, glucagon, C peptide and glp 1 and lipid when diets are tested (three acute tests with diets). After that, the patient will begin the drug by month (Januvia, 100 mg a day)and repeat all the three curves using the prepared diets to compare with the first month.
Drug: Dipeptidyl Peptidase IV inhibitors
Dosage 100 mg each day, once a day, 2 months
Other Names:
  • Januvia (Merck Sharp Dome)
  • Sitagliptin
Active Comparator: 2
Since the beginning they will use the drug. Then will make the three tests and after will stop the drug by 1 month and come back to do the tests. We objective to demonstrate the washout of the drug clinically.
Drug: Dipeptidyl Peptidase IV inhibitors
Dosage 100 mg each day, once a day, 2 months
Other Names:
  • Januvia (Merck Sharp Dome)
  • Sitagliptin

Detailed Description:

It is well known that there is a progressive deterioration in beta-cell function over time in type 2 diabetes (DM2), as indicated by the UKPDS (United Kingdom Prospective Diabetes Study), regardless of therapy allocation, albeit conventional (mainly diet), insulin, chlorpropamide, glibenclamide or metformin treatment. Moreover, the pancreatic islet function was found to be about 50% of normal at the time of diagnosis, independent of the degree of insulin resistance, with the reduction in function probably commencing 10-12 years prior to diagnosis and aggravated by increasing fasting plasma glucose levels.

Optimal metabolic control, especially early intensive glycemic control, plays a role in the prevention of progressive beta cell dysfunction and possibly destruction of the betacells with worsening of diabetes. Many reports have shown that induction of normoglycemia in DM2 results in both improved beta cell function and insulin resistance.The major therapeutic drawback using native GLP-1 is its very short half-life of less than 2 minutes, following exogenous administration, as previously indicated due in part to the protease DDP-IV a result, preventing the degradation of native GLP-1 by inhibiting the active of the DDP-IV enzyme has emerged as a therapeutic strategy for enhancing endogenous GLP-1 action in vivo.Considering that, sitagliptin is the first FDA and ANVISA authorized dipeptidyl peptidase-IV (DPP-IV) inhibitor for diabetes treatment and considering the lack of data about DPP-IV inhibitor effect over glucose, glucagon, insulin, C -peptide and fats after isocaloric diets with different nutritional composition in drug näive patients with type 2 diabetes, we designed this study.

  Eligibility

Ages Eligible for Study:   40 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Drug näive patients with T2DM (for the purpose of this study "drug näive" patients are defined as subjects who have never been treated with an oral antidiabetic agent or subjects who have not taken any antidiabetic agent for at least 12 weeks prior to study entry (Visit 1) and if they had never received antidiabetic agents then never for > 3 months at any time in the past).
  • Age in the range of 18 - 78 years inclusive.
  • Male, non-fertile female or female of childbearing potential using a medically approved birth control method. 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 >40mlU/m)
    • 6 weeks post bilateral oophorectomy with or without hysterectomy
    • post hysterectomy
    • or sterilized by tubal ligation.
  • Written informed consent to participate in the study.
  • Ability to comply with all study requirements.

Exclusion Criteria:

  • Pregnant or lactating female
  • A history of type 1 diabetes, diabetes that is 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.
  • Evidence of significant diabetic complications, e.g., symptomatic autonomic neuropathy or gastroparesis.
  • Acute infections wich 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.
  • Any of the following within the past 6 months:

    • myocardial infarction (MI) (if the visit one 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.
  • Congestive heart failure (CHF) requiring pharmacological treatment.
  • Any of the following EGC abnormalities; "Torsades de points", 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)
  • Malignancy including leukemia and lymphoma (not including basal cell skin cancer) within the last 5 years.
  • Liver disease such as cirrhosis or chronic active hepatitis.
  • Donation of one unit ( 500ml) or more of blood, significant blood loss equaling to at least one unit of blood within the past 2 weeks or a blood transfusion within the past 8 weeks.
  • Chronic insulin (>4 weeks of treatment in the absence of an intercurrent illness) within the past 6 month.
  • Chronic oral or parenteral corticosteroid treatment ( > 7 consecutive days of treatment) within 8 weeks prior to visit 1.
  • Treatment with growth hormone or similar drugs.
  • Treatment with class Ia, Ib and Ic or III anti-arrhythmics.
  • Patients who have already been in a study of sitagliptin or another DPP 4 inhibitor.
  • Use of other investigational drugs at visit 1, or within 30 days or 5 half-lives of visit 1.
  • Any of the following significant laboratory abnormalities:

    • ALT, AST greater than 3 times the upper limit of the normal range at visit 1. *clinically significant renal dysfunction as indicated by serum creatinine levels > or equal 1,5mg/dl in males, > or equal 1,4 mg/dl in females, or a history of abnormal creatinine clearance < 60 ml/m2/24h
    • clinically significant TSH values outside of normal range at visit 1
    • clinically significant laboratory abnormalities, confirmed by repeated measurement, other than hyperglycemia, hyperinsulinemia, and glycosuria at visit 1.
    • fasting triglycerides > 700 mg / dl at visit 1.
  • History of active substance abuse (including alcohol) within the past 2 years.
  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: NCT00881543

Locations
Brazil
University of São Paulo General Hospital
São Paulo, Brazil
Sponsors and Collaborators
University of Sao Paulo General Hospital
University of Sao Paulo
Investigators
Principal Investigator: Cristina S Oliveira, Pos Grad Sao Paulo General Hospital
Study Director: Bernardo L Wajchenberg, PhD Sao Paulo General Hospital
  More Information

No publications provided

Responsible Party: Nanci Valeis, Colaborator, University of Sao Paulo General Hospital
ClinicalTrials.gov Identifier: NCT00881543     History of Changes
Other Study ID Numbers: USaoPauloGH
Study First Received: April 14, 2009
Last Updated: May 24, 2012
Health Authority: Brazil: Ethics Committee

Keywords provided by University of Sao Paulo General Hospital:
Sitagliptin
Diets
Diabetes type 2
Näive patients

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 2
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Sitagliptin
Dipeptidyl-Peptidase IV Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Hypoglycemic Agents
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on July 23, 2014