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

NCT ID: NCT00881543

Last Updated: 2012-05-28

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 45 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-06-30
• Study Completion Date: 2011-10-31

Brief Summary

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.

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.

Conditions

Diabetes Type 2

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: PLACEBO_COMPARATOR

Dipeptidyl Peptidase IV inhibitors

Intervention Type: DRUG

Dosage 100 mg each day, once a day, 2 months

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.

Group Type: ACTIVE_COMPARATOR

Dipeptidyl Peptidase IV inhibitors

Intervention Type: DRUG

Dosage 100 mg each day, once a day, 2 months

Interventions

Dipeptidyl Peptidase IV inhibitors

Dosage 100 mg each day, once a day, 2 months

Intervention Type: DRUG

Other Intervention Names

Januvia (Merck Sharp Dome); Sitagliptin

Eligibility 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.

• Minimum Eligible Age: 40 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Sao Paulo

OTHER

Sponsor Role: collaborator

University of Sao Paulo General Hospital

OTHER

Sponsor Role: lead

Responsible Party

Nanci Valeis

Colaborator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Cristina S Oliveira, Pos Grad

Role: PRINCIPAL_INVESTIGATOR

Sao Paulo General Hospital

Bernardo L Wajchenberg, PhD

Role: STUDY_DIRECTOR

Sao Paulo General Hospital

Locations

University of São Paulo General Hospital

São Paulo, São Paulo, Brazil

Countries

Brazil

References

da Silva Schreiber C, Rafacho A, Silverio R, Betti R, Lerario AC, Lotenberg AMP, Rahmann K, de Oliveira CP, Wajchenberg BL, da Luz PL. The effects of macronutrients composition on hormones and substrates during a meal tolerance test in drugnaive and sitagliptin-treated individuals with type 2 diabetes: a randomized crossover study. Arch Endocrinol Metab. 2022 May 13;66(3):312-323. doi: 10.20945/2359-3997000000478. Epub 2022 May 12.

Reference Type: DERIVED

PMID: 35551683 (View on PubMed)

Other Identifiers

USaoPauloGH

Identifier Type: -

Identifier Source: org_study_id