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Pharmacokinetics Study of Dipeptidyl Peptidase 4 Inhibitor to Control Type 2 Diabetes Mellitus

10. november 2015 opdateret af: Ji Hyun Kim, The Catholic University of Korea

Mechanism of Reduced Response to DPP-4 Inhibitor in Patients With Type 2 Diabetes Mellitus

The purpose of this study is to confirm the mechanism of reduced response to DPP-4 inhibitor in some patients with type 2 diabetes and evaluate appropriate patients to treat with DPP-4 inhibitor

Studieoversigt

Status

Afsluttet

Betingelser

Intervention / Behandling

Detaljeret beskrivelse

Sitagliptin, a DPP-4 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-4 inhibitor in some type 2 diabetes patients. Firstly, significantly reduced secretion of glucagon-like peptide 1 (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-4. Secondly, mutation or functional defect of DPP-4 enzyme could not be inhibited by DPP-4 inhibitor. Thirdly, GLP-1 receptor mutation or other defect in β-cell responsiveness to GLP-1 leads to reduction of response to DPP-4 inhibitor.

Undersøgelsestype

Interventionel

Tilmelding (Faktiske)

24

Fase

  • Fase 4

Kontakter og lokationer

Dette afsnit indeholder kontaktoplysninger for dem, der udfører undersøgelsen, og oplysninger om, hvor denne undersøgelse udføres.

Studiesteder

  • Korea, Republikken
      • Seoul, Korea, Republikken, 130-709
        • The Catholic University of Korea; St.Paul's Hospital
      • Seoul, Korea, Republikken, 137-701
        • The Catholic University of Korea; Seoul St. Mary's Hospital

Deltagelseskriterier

Forskere leder efter personer, der passer til en bestemt beskrivelse, kaldet berettigelseskriterier. Nogle eksempler på disse kriterier er en persons generelle helbredstilstand eller tidligere behandlinger.

Berettigelseskriterier

Aldre berettiget til at studere

20 år til 70 år (Voksen, Ældre voksen)

Tager imod sunde frivillige

Ingen

Køn, der er berettiget til at studere

Alle

Beskrivelse

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 thiazolidinediones, alpha-glucosidase inhibitors, GLP-1 analogue or DPP-4 inhibitors
  • Patients with renal, hepatic dysfunction
  • Patients with diabetic complications such as coronary heart disease, cerebrovascular disease, proliferative diabetic retinopathy or diabetic gastroparesis
  • Patients taking medications affecting glucose level

Studieplan

Dette afsnit indeholder detaljer om studieplanen, herunder hvordan undersøgelsen er designet, og hvad undersøgelsen måler.

Hvordan er undersøgelsen tilrettelagt?

Design detaljer

  • Primært formål: Behandling
  • Tildeling: Ikke-randomiseret
  • Interventionel model: Parallel tildeling
  • Maskning: Ingen (Åben etiket)

Våben og indgreb

Deltagergruppe / Arm
Intervention / Behandling
Aktiv komparator: study group
sitagliptin hypo-response patients
Medicin: Sitagliptin
Sitagliptin (100mg, per oral) once a day.
Andre navne:
  • Januvia
Sham-komparator: control group
sitagliptin response patients
Medicin: Sitagliptin
Sitagliptin (100mg, per oral) once a day.
Andre navne:
  • Januvia

Hvad måler undersøgelsen?

Primære resultatmål

Resultatmål
Foranstaltningsbeskrivelse
Tidsramme
Plasma Concentration of Active Glucagon-like Peptide 1 (GLP-1) Before and After Sitagliptin Treatment
Tidsramme: 0, 15, 30, 45, 60, 90, 120, 180 min pre and post-dose
Plasma concentrations of active GLP-1 were measured at 0, 15, 30, 45, 60, 90, 120 and 180 min during the meal tolerance test (MTT). Second measurement of active GLP-1 were measured with MTT after taking sitagliptin 100 mg 1 hour before the test.
0, 15, 30, 45, 60, 90, 120, 180 min pre and post-dose
Plasma Concentration of Total GLP-1 Before and After Sitagliptin Treatment
Tidsramme: 0, 15, 30, 45, 60, 90, 120, 180 min pre and post-dose
Plasma concentrations of total GLP-1 were measured at 0, 15, 30, 45, 60, 90, 120 and 180 min during the meal tolerance test. Second measurement of total GLP-1 were measured with MTT after taking sitagliptin 100 mg 1 hour before the test.
0, 15, 30, 45, 60, 90, 120, 180 min pre and post-dose
Plasma Concentration of Total Glucose-dependent Insulinotropic Polypeptide (GIP) Before and After Sitagliptin Treatment
Tidsramme: 0, 15, 30, 45, 60, 90, 120, 180 min pre and post-dose
Plasma concentrations of total GIP were measured at 0, 15, 30, 45, 60, 90, 120 and 180 min during the meal tolerance test. Second measurement of total GIP were measured with MTT after taking sitagliptin 100 mg 1 hour before the test.
0, 15, 30, 45, 60, 90, 120, 180 min pre and post-dose
Change in AUC of Active GLP-1, Total GLP-1 and Total GIP Between Before and After Sitagliptin Treatment
Tidsramme: 0, 15, 30, 45, 60, 90, 120, 180 min pre and post-dose
Plasma concentrations of active GLP-1, total GLP-1 and total GIP were measured at 0, 15, 30, 45, 60, 90, 120 and 180 min during the meal tolerance test. Second measurements were measured with MTT after taking sitagliptin 100 mg 1 hour before the test. Comparisons were made using Area under the curve (AUC) values and incremental area under the curve (ΔAUC) of active GLP-1, total GLP-1 and total GIP before and after the addition of sitagliptin.
0, 15, 30, 45, 60, 90, 120, 180 min pre and post-dose

Sekundære resultatmål

Resultatmål
Foranstaltningsbeskrivelse
Tidsramme
Differences of DPP-4 Activity After Sitagliptin Treatment Between Responder and Non-responder Groups
Tidsramme: 0, 15, 30, 45, 60 min post-dose
The DPP-4 activity was measured at baseline and 0, 15, 30, 45 and 60 min during the meal tolerance test. Second measurement of DPP-4 activity was measured with MTT after taking sitagliptin 100 mg 1 hour before the test. Plasma DPP-4 activity during meal tolerance test is expressed as percentage activity relative to baseline. DPP-4 activity % was calculated using the following formula : (DPP-4 activity at time t / Baseline DPP-4 activity) × 100.
0, 15, 30, 45, 60 min post-dose

Samarbejdspartnere og efterforskere

Det er her, du vil finde personer og organisationer, der er involveret i denne undersøgelse.

Sponsor

The Catholic University of Korea

Samarbejdspartnere

Merck Sharp & Dohme LLC

Efterforskere

  • Ledende efterforsker: Ji Hyun Kim, Dr, The Catholic University of Korea

Datoer for undersøgelser

Disse datoer sporer fremskridtene for indsendelser af undersøgelsesrekord og resumeresultater til ClinicalTrials.gov. Studieregistreringer og rapporterede resultater gennemgås af National Library of Medicine (NLM) for at sikre, at de opfylder specifikke kvalitetskontrolstandarder, før de offentliggøres på den offentlige hjemmeside.

Studer store datoer

Studiestart

1. december 2011

Primær færdiggørelse (Faktiske)

1. august 2014

Studieafslutning (Faktiske)

1. juli 2015

Datoer for studieregistrering

Først indsendt

29. september 2011

Først indsendt, der opfyldte QC-kriterier

7. oktober 2011

Først opslået (Skøn)

10. oktober 2011

Opdateringer af undersøgelsesjournaler

Sidste opdatering sendt (Skøn)

14. december 2015

Sidste opdatering indsendt, der opfyldte kvalitetskontrolkriterier

10. november 2015

Sidst verificeret

1. november 2015

Mere information

Begreber relateret til denne undersøgelse

Nøgleord

Yderligere relevante MeSH-vilkår

Andre undersøgelses-id-numre

  • CMCENDO-01

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Kliniske forsøg med Type 2 diabetes mellitus

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