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Type 2 Diabetes MellitusPhase 1NCT00551590

Effect of Sitagliptin on Incretin Effect in Patients With Type 2 Diabetes Mellitus

A Phase 1 study testing Sitagliptin tablet, Saline infusion and Exendin(9-39) infusion in people with Type 2 Diabetes Mellitus, run by Ludwig-Maximilians - University of Munich at 1 site in Germany.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

The purpose of this study is to assess the effect of the DPP-4 inhibitor sitagliptin on the incretin effect in patients with type 2 diabetes mellitus. Read more about this study

Who is it for?
Ages 30 to 70 years
Conditions the study is for
Type 2 Diabetes Mellitus
What is being tested?
Sitagliptin tablet, Saline infusion and Exendin(9-39) infusion
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
24 participants
Where
1 siteGermany
Study dates
Dec 2007to Sep 2011
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 30 to 70 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Women with T2DM without childbearing potential
  • Male patients with T2DM using a double-barrier method of contraception
  • must be able to complete a 1 week wash-out of current anti-diabetic medications (patients on PPARγ must be off for at least 4 weeks)
  • no medications which may alter gastric motility (i.e. acetaminophen, erythromycin) except for cardiac medication at a stable dose.
  • Age 30-70 years
  • HbA1c ≤9% at screening
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  • BMI<40 kg/m2
  • Must have a fasting blood glucose of ≤11.1 mmol/L (200 mg/dL) at screening
  • Able to provide written informed consent prior to study participation
  • Able to communicate well with the investigator and comply with the requirements of the study
  • Able to maintain dietetic restrictions and to perform measurements of blood glucose on a daily basis (fasting and two-hours postprandial). Patients must be informed the investigator if fasting glucose is above 200mg/dl or two hours postprandially blood glucose concentration above 240mg/dl is being measured.

Who cannot join

  • T1DM, diabetes as a result of pancreatic injury, or secondary forms of diabetes (eg. Cushing, acromegaly)
  • Females with childbearing potential, breastfeeding and pregnant women
  • Need for insulin within the previous 3 months
  • Use of Thiazolidinediones in the previous 4 weeks
  • Significant concomitant disease or complications of diabetes (i.e. nephropathy, autonomic dysfunction, orthostasis).
  • Fasting triglycerides >5.1 mmol/L (>450 mg/dL) within the past 4 weeks.
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  • Treatment with systemic steroids and thyroid hormone (unstable dosage).
  • Patients with any history of gastrointestinal surgery, e.g. partial bowel resections, partial gastric resections, etc.
  • Participation in any clinical investigation within 4 weeks prior to dosing or longer if required by local regulation.
  • Donation or loss of 400 mL or more of blood within 8 weeks prior to dosing.
  • Significant illness within the two weeks prior to dosing.
  • Past medical history of clinically significant ECG abnormalities or a family history of a prolonged QT-interval syndrome.
  • History of clinically significant drug allergy; history of atopic allergy (asthma, urticaria, eczematous dermatitis). A known hypersensitivity to the study drug or drugs similar to the study drug.
  • Any surgical or medical condition which might significantly alter the absorption, distribution, metabolism or excretion of drugs or which may jeopardize the subject in case of participation in the study. The investigator should be guided by evidence of any of the following:
  • history of inflammatory bowel syndrome, gastritis, ulcers, gastrointestinal or rectal bleeding;
  • history of major gastrointestinal tract surgery such as gastrectomy, gastroenterostomy, or bowel resection;
  • history or clinical evidence of pancreatic injury or pancreatitis;
  • history or presence of impaired renal function as indicated by abnormal creatinine or urea val-ues or abnormal urinary constituents (e.g., albuminuria);
  • evidence of urinary obstruction or difficulty in voiding at screening;
  • Polymorphonuclears <1500/µL at inclusion or platelet count < 100,000/μL at screening and base-line.
  • History of immunocompromise.
  • Evidence of liver disease as indicated by abnormal liver function tests such as SGOT, SGPT, GGT, alkaline phosphatase, or serum bilirubin. SGOT, SGPT, GGT and alkaline phosphatase must not exceed twice the upper limit of the normal range, and serum bilirubin should not exceed the value of 27 µmol/L (1.6 mg/dL).
  • History of drug or alcohol abuse within the 12 months prior to dosing or evidence of such abuse as indicated by the laboratory assays conducted during the screening evaluations.

Trial locations and contacts

1 site in 1 country.

Germany1 site

  • Clinical Research unit, Dept. of Internal Medicine II - Großhadern, University of Munich

    Munich, 81377

Other trials in Germany

About this study

Official title: A Randomized, Placebo-Controlled, 4-period, Crossover Study to Assess the Impact of MK-0431 (Sitagliptin) on Incretin Effect and the Role of Specific Incretin Hormones in Patients With Type 2 Diabetes Mellitus

The purpose of this study is to assess the effect of the DPP-4 inhibitor sitagliptin on the incretin effect in patients with type 2 diabetes mellitus.

Read the detailed description

Following a meal, gut-produced incretin hormones such as glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) are released into the circulation. Because GLP-1 and GIP mediate grossly 60% of the insulin-stimulatory action, the so-called incretin effect, both are crucial components of a natural endogenous system guaranteeing glucose homeostasis. In addition, GLP-1 lowers glucagon secretion from pancreatic alpha-cells and delays nutrient delivery from the stomach by inhibiting gastric emptying. The rise in insulin concentration enhances glucose clearance in peripheral tissues such as muscle, and the lower glucagon concentration combined with the rise in insulin reduces hepatic glucose production. By enhancing glucose clearance and lowering hepatic glucose production, the post-meal glucose excursion is reduced.

Both GLP-1 and GIP are degraded by the enzyme dipeptidylpeptidase-4 (DPP-4). Inhibition of DPP-4 by the specific DPP-4 inhibitor Sitagliptin increases plasma levels of both GLP-1 and GIP, and reduces postprandial glycemia.

Although important in healthy subjects, the role of the incretin hormones in patients with T2DM is unclear. In T2DM the insulinotropic efficacy of GIP is reduced and the postprandial release of GLP-1 is diminished.

Therefore, the aim of this study in T2DM is to quantify the incretin effect with and without the DPP-4 inhibitor sitagliptin. The specific GLP-1 receptor antagonist exendin(9-39) will be used to quantify the contribution of both GLP-1 and GIP to the incretin effect in patients with T2DM.

Being tested
Placebo tablet, Sitagliptin tablet, Saline infusion, Exendin(9-39) infusion
Keywords
diabetes mellitus, DPP-4 inhibitor, sitagliptin, exendin(9-39), GLP-1
Medical subject headings
Diabetes Mellitus, Type 2, Diabetes Mellitus

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Placebo tabletDrug

    placebo PO (placebo control for sitagliptin) for three days

  • Sitagliptin tabletDrug

    Sitagliptin 100 mg PO for three days.

  • Saline infusionDrug

    Saline IV (placebo control for exendin(9-39)) on two consecutive study days

  • Exendin(9-39) infusionDrug

    Exendin(9-39) IV on two consecutive study days.

Study groups in NCT00551590
Study groupRoleWhat they receive
1Placebo comparatorplacebo PO (placebo control for sitagliptin) for three days. Saline IV (placebo control for exendin(9-39) on two consecutive study days.
Receives: Drug: Placebo tablet; Drug: Saline infusion
2ExperimentalSitagliptin 100 mg PO for three days. Saline IV (placebo control for exendin(9-39)) on two consecutive study days
Receives: Drug: Sitagliptin tablet; Drug: Saline infusion
3ExperimentalSitagliptin 100 mg PO for three days. Exendin(9-39) IV on two consecutive study days.
Receives: Drug: Sitagliptin tablet; Drug: Exendin(9-39) infusion
4Placebo comparatorplacebo PO (placebo control for sitagliptin) for three days. Exendin(9-39)IV on two consecutive study days.
Receives: Drug: Placebo tablet; Drug: Exendin(9-39) infusion

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. To asses the effect of sitagliptin compared to placebo and to coadministration of sitagliptin and the GLP-1 receptor antagonist exendin(9-39)NH2 on the incretin effect after an oral glucose challenge.

    Measured: during 240 minutes after ingestion of an OGTT

Secondary outcomes (1)

  1. Plasma glucagon, plasma GIP, plasma GLP-1, Insulin, C-peptide, plasma glucose profiles. 13CO2 exhalation kinetics assessing gastric emptying

    Measured: during 240 minutes after ingestion of an OGTT

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted31 Oct 2007 (estimated)
  2. Study startDec 2007
  3. Primary completionDec 2008
  4. Study completionSep 2011

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Diagnosis
Allocation
Randomised
Intervention model
Crossover
Masking
Double blind
Who is masked
Participant, Investigator
Enrolment
24 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00551590
Sponsor's protocol ID
SITEX-02
Other IDs
EudraCT 2007-001050-83
Status last verified
Oct 2011
First submitted
30 Oct 2007
Last updated
4 Oct 2011
Results posted
No
Data monitoring committee
Yes

Publications

  • Schirra J, Sturm K, Leicht P, Arnold R, Goke B, Katschinski M. Exendin(9-39)amide is an antagonist of glucagon-like peptide-1(7-36)amide in humans. J Clin Invest. 1998 Apr 1;101(7):1421-30. doi: 10.1172/JCI1349.

    PubMed 9525985

  • Schirra J, Nicolaus M, Roggel R, Katschinski M, Storr M, Woerle HJ, Goke B. Endogenous glucagon-like peptide 1 controls endocrine pancreatic secretion and antro-pyloro-duodenal motility in humans. Gut. 2006 Feb;55(2):243-51. doi: 10.1136/gut.2004.059741. Epub 2005 Jun 28.

    PubMed 15985560

  • Nauck M, Stockmann F, Ebert R, Creutzfeldt W. Reduced incretin effect in type 2 (non-insulin-dependent) diabetes. Diabetologia. 1986 Jan;29(1):46-52. doi: 10.1007/BF02427280.

    PubMed 3514343

  • Aulinger BA, Bedorf A, Kutscherauer G, de Heer J, Holst JJ, Goke B, Schirra J. Defining the role of GLP-1 in the enteroinsulinar axis in type 2 diabetes using DPP-4 inhibition and GLP-1 receptor blockade. Diabetes. 2014 Mar;63(3):1079-92. doi: 10.2337/db13-1455. Epub 2013 Dec 2.

    PubMed 24296715

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Sitagliptin tablet, Saline infusion and Exendin(9-39) infusion in people with Type 2 Diabetes Mellitus, run by Ludwig-Maximilians - University of Munich at 1 site in Germany.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 11 inclusion and 23 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 4 Oct 2011. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Germany. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

To asses the effect of sitagliptin compared to placebo and to coadministration of sitagliptin and the GLP-1 receptor antagonist exendin(9-39)NH2 on the incretin effect after an oral glucose challenge. (time frame: during 240 minutes after ingestion of an OGTT). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00551590, which also lists 4 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Oct 2011.

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