Pharmacokinetics Study of DPP-4 Inhibitor to Control Type 2 Diabetes Mellitus

The recruitment status of this study is unknown because the information has not been verified recently.
Verified October 2011 by The Catholic University of Korea.
Recruitment status was  Not yet recruiting
Sponsor:
Collaborator:
Merck Sharp & Dohme Corp.
Information provided by (Responsible Party):
Ji Hyun Kim, The Catholic University of Korea
ClinicalTrials.gov Identifier:
NCT01449747
First received: September 29, 2011
Last updated: October 7, 2011
Last verified: October 2011
  Purpose

The purpose of this study is to confirm the mechanism of reduced response to DPP-IV inhibitor in some patients with type 2 diabetes and evaluate appropriate patients to treat with DPP-IV inhibitor


Condition Intervention Phase
Type 2 Diabetes Mellitus
Drug: Sitagliptin
Phase 4

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Bio-availability Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Mechanism of Reduced Response to DPP-4 Inhibitor in Patients With Type 2 Diabetes Mellitus

Resource links provided by NLM:


Further study details as provided by The Catholic University of Korea:

Primary Outcome Measures:
  • Profile of Pharmacokinetics [ Time Frame: 0, 15, 30, 45, 60, 90, 120, 180 min post-dose ] [ Designated as safety issue: No ]
    Area under curve(AUC tGLP-1, AUC iGLP-1, AUC tGIP)


Secondary Outcome Measures:
  • Profile of Pharmacokinetics [ Time Frame: 0, 15, 30, 45, 60 min post-dose ] [ Designated as safety issue: No ]
    Area under curve (DPP-4)


Estimated Enrollment: 24
Study Start Date: November 2011
Estimated Study Completion Date: June 2012
Estimated Primary Completion Date: March 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: study group
sitagliptin hypo-response patients
Drug: Sitagliptin
Sitagliptin (100mg, per oral) once a day.
Other Name: Januvia
Sham Comparator: control group
sitagliptin response patients
Drug: Sitagliptin
Sitagliptin (100mg, per oral) once a day.
Other Name: Januvia

Detailed Description:

Sitagliptin, a DPP-IV inhibitor was used as an incretin enhancer in clinical practice first. In clinical trials, sitagliptin showed effective control of blood glucose level in type 2 diabetes and 100 mg once daily with metformin was similar to sulfonylurea (glipizide) with metformin in lowering HbA1c. Mostly in practice, stable blood glucose levels were maintained after change of sulfonylurea to sitagliptin in type 2 diabetes treatment. However, in some cases, there were abrupt severe hyperglycemia and uncontrolled blood glucose level after drug change to sitagliptin.

Several mechanism could be considered for reduced response to DPP-IV inhibitor in some type 2 diabetes patients. Firstly, significantly reduced secretion of GLP-1 more than expected in diabetes or functional defect of GLP-1 activity could be the mechanism of loss of GLP-1 effect irrespective of DPP-IV. Secondly, mutation or functional defect of DPP-IV enzyme could not be inhibited by DPP-VI inhibitor. Thirdly, GLP-1 receptor mutation or other defect in β-cell responsiveness to GLP-1 leads to reduction of response to DPP-IV inhibitor.

  Eligibility

Ages Eligible for Study:   20 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Type 2 diabetic patients with less than 15 yrs of disease duration
  • BMI between 22-27 kg/m2
  • HbA1c ≤ 9% at recruitment

    1. Study group

After change sulfonylurea to sitagliptin in case of metformin and sulfonylurea therapy

  1. Increase of fasting blood glucose over 20 mg/dL or postprandial glucose over 30 mg/dL within several days or
  2. Increase of HbA1c over 1% within 2-3 months without abrupt increase of blood glucose levels within several days

    • Sulfonylurea dose : less than glimepiride 4mg or gliclazide 120mg or glibenclamide 10mg
    • Metformin dose : 500~2000mg
  3. Reduced response to sitagliptin should be made a decision by investigators after understanding the condition of patients surely.

2. Control group

  • Age, sex, BMI matched patients with same condition of study patients
  • After change sulfonylurea to sitagliptin in case of metformin plus sulfonylurea therapy, no change of blood glucose levels like above or stable HbA1c change within 1% within 2-3 months

Exclusion Criteria:

  • Other causes of increase of blood glucose levels except drug change
  • Patients with history of insulin treatment
  • Patients taking TZDs, alpha-glucosidase inhibitors, GLP-1 analogue or DPP-IV inhibitors
  • Patients with renal, hepatic dysfunction
  • Patients with diabetic complications such as CHD, CVD, PDR or diabetic gastroparesis
  • Patients taking medications affecting glucose level
  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: NCT01449747

Contacts
Contact: Ji Hyun Kim, M.D. 82-2-961-4534 kjhyun@catholic.ac.kr
Contact: Kun Ho Yoon, M.D., Ph.D. 82-2-2258-7573 yoonk@catholic.ac.kr

Locations
Korea, Republic of
The Catholic University of Korea; St.Paul's Hospital Not yet recruiting
Seoul, Korea, Republic of, 130-709
Contact: Ji Hyun Kim    82-2-961-4534    kjhyun@catholic.ac.kr   
Principal Investigator: Ji Hyun Kim, M.D.         
The Catholic University of Korea; Seoul St. Mary's Hospital Not yet recruiting
Seoul, Korea, Republic of, 137-701
Contact: Kun Ho Yoon    82-2-2258-7573    yoonk@catholic.ac.kr   
Principal Investigator: Kun Ho Yoon         
Sponsors and Collaborators
The Catholic University of Korea
Merck Sharp & Dohme Corp.
Investigators
Principal Investigator: Ji Hyun Kim, Dr The Catholic University of Korea
  More Information

No publications provided

Responsible Party: Ji Hyun Kim, Clinical Assistant Professor, The Catholic University of Korea
ClinicalTrials.gov Identifier: NCT01449747     History of Changes
Other Study ID Numbers: CMCENDO-01
Study First Received: September 29, 2011
Last Updated: October 7, 2011
Health Authority: Korea: Institutional Review Board

Keywords provided by The Catholic University of Korea:
Type 2 diabetes mellitus
Dipeptidyl peptidase IV inhibitors
Glucagon-like peptide 1

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 28, 2014