Type 2 DiabetesPhase 3NCT01937598
Antidiabetic Effects of Adding a DPP-4 Inhibitor to Pre-Existing Treatment With an Incretin Mimetic in Patients With T2D
A Phase 3 study testing Mixed meal test, Liraglutide and Sitagliptin in people with Type 2 Diabetes, run by Michael A. Nauck at 1 site in Germany.
Trial summary
Objectives: To quantify differences in control of glycemia (primary objective) and the secretion of endogenous incretin hormones (secondary objective) comparing sitagliptin or placebo added to pre-existing therapy with liraglutide and metformin Read more about this study
- Who is it for?
- Ages 25 to 75 years
- Conditions the study is for
- Type 2 Diabetes
- What is being tested?
- Mixed meal test, Liraglutide and Sitagliptin
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 16 participants
- Where
- 1 siteGermany
- Study dates
- Aug 2013to Jun 2015
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 25 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Signed \& dated written informed consent
- Male \& female subjects with a diagnosis of type 2 diabetes mellitus according to ADA criteria at least 4 months prior to screening
- Medical history without major pathology (with the exception of type 2 diabetes) as judged by the investigator
- On a stable regimen of metformin for at least 1 month and liraglutide 1.2 mg for at least 1 week at the time-point of randomisation.
- Age: 25 - 75 years, both inclusive
- Body mass index (BMI): 22 - 40kg/m^2, both inclusive
- HbA1c ≥ 6.5 and ≤ 8.5% (≥ 7.0 and ≤ 8.5% for patients without previous liraglutide treatment)
- Female must be post-menopausal, surgically sterilized or practicing an effective birth control
Who cannot join
- Subjects with type 1 diabetes, maturity onset diabetes of the young (MODY) or secondary forms of diabetes such as due to pancreatitis
- Current or previous treatment with insulin therapy (except for treatment at diabetes' diagnosis, within a clinical trial, for surgical procedures or during an acute illness, and no insulin administration within the 6 months before screening)
- Treatment with any hypoglycaemic medication other than metformin and liraglutide within one month prior to screening
- Known of diabetic gastroparesis and / or prokinetic therapy
- Subjects that underwent surgery of the upper gastrointestinal tract
- Women who are pregnant, intending to become pregnant during the study period, currently lactating females, or women of child-bearing potential not using highly effective, medically approved birth control methods
Show all 27Show fewer
- Any severe medical or surgical history of conditions likely to confound study assessments or study endpoints, for example but not limited to haemoglobinopathies, inflammatory bowel disease, cystic fibrosis, bariatric surgery and/or any surgery shortening the intestine, history of lactose intolerance, lactose- or glucose-galactose-malabsorption
- A suspicion of medullary thyroid cancer or a multiple endocrine neoplasia
- A personal or family history of medullar thyroid cancer or a multiple endocrine neoplasia
- Serious and/or unstable coronary heart disease (unstable angina, myocardial infarction within the preceding 6 months), congestive heart failure of New York Heart Association Class III or worse (severe limitation of physical activity; physical activity of low intensity resulting in fatigue, palpitation, or dyspnoea), second/third degree heart block, superior vena cava syndrome, uncontrolled hypertension, history of congenital QT-syndrome within family, history of stroke (within the preceding 6 months) or serious peripheral vascular disease
- History of arrhythmia (multifocal premature ventricular contractions, bigeminy, trigeminy, ventricular tachycardia, or uncontrolled atrial fibrillation) that is symptomatic or requires treatment (grade 3), left bundle branch block, or asymptomatic sustained ventricular tachycardia are not allowed
- Marked diabetic complications: severe autonomic or sensory neuropathy including previously diagnosed gastroparesis; proliferative retinopathy
- Any respiratory disease leading to respiratory insufficiency and/or depression including but not limited to clinically significant: bronchial asthma, chronic obstructive pulmonary disease, that might impact to the breath test, as judged by the investigator
- Clinically significant vital signs including known bradycardia with pulse rate < 50/min or 12-lead ECG findings including QTc (corrected QT interval) > 450 msec for males or QTc > 470 msec for women
- Clinically significant abnormal haematology, biochemistry, lipids, or urinalysis or coagulation screening tests, as judged by the Investigator
- Moderate or severe renal dysfunction defined as an estimated creatinine clearance (MDRD equation) GFR (glomerular filtration rate) <50 ml/min.
- Clinical or laboratory evidence of hepatic dysfunction or disease; laboratory evidence defined as any of the following parameters: alkaline phosphatase, ALT , AST or bilirubin > 3x ULN (upper Limit of normal). Isolated mild rise in bilirubin considered to be due to Gilbert's condition is allowed
- Uncontrolled high blood pressure (DBP (diastolic blood pressure) > 95 mmHg and/or SBP (systolic blood pressure) > 160 mmHg), unless clearly documented to be white-coat hypertension
- History of any psychiatric condition that might impair the subject's ability to understand or to comply with the requirements of the study or to provide informed consent
- History of relevant drug and/or food allergies or a history of severe anaphylactic reaction
- Currently active or history of alcohol abuse (defined as an intake of more than 24 units of alcohol per week; one unit of alcohol equals approximately 250 mL of beer, 100 mL of wine or 35 mL of spirits) or drug addiction (including soft drugs like cannabis products)
- Use of concomitant medication which would be likely to interact with metformin, sitagliptin or liraglutide (according to the subject information leaflet). Participation in another study within the 3 months preceding screening or 5-half-lives of drug studied, whichever is longer, prior to study drug administration
- Malignancy within 5 years of study start, except for successfully treated local basal cell carcinomas
- Known to be positive for Hepatitis B surface antigen or Hepatitis C antibodies (or diagnosed with active hepatitis according to local practice)
- Subject who has donated or lost > 500 mL blood within 3 months prior to screening \& has a Hb < 14 g/dl at screening
- History of hypersensitivity to the study drug or any of the excipients or to medicinal products with similar chemical structures
- Veins unsuitable for repeated venipuncture
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Antidiabetic Effects of Adding a DPP-4 Inhibitor (Sitagliptin) to Pre-Existing Treatment With an Incretin Mimetic (Liraglutide) in Patients With Type 2 Diabetes Treated With Metformin
Objectives: To quantify differences in control of glycemia (primary objective) and the secretion of endogenous incretin hormones (secondary objective) comparing sitagliptin or placebo added to pre-existing therapy with liraglutide and metformin
Read the detailed description
This is a double blind, controlled, cross-over comparison of adding sitagliptin (or placebo) to pre-existing metformin+liraglutide therapy. Patients with type 2 diabetes mellitus (T2DM) on pre-existing treatment with metformin (≥ 1500 mg/d) monotherapy or metformin plus liraglutide (1.2 mg/d) will be studied. Patients on metformin monotherapy will, after screening and randomization, enter a run-in period of 2 weeks with the additional treatment of liraglutide (0.6 mg/d for 1 week followed by 1.2 mg/d for another week). At the end of this 2 weeks therapy, a mixed meal challenge will take place, with the assessment of glucose and hormone responses (insulin, C-peptide, glucagon, GLP-1 [glucagon-like peptide-1], GIP (gastric inhibitory peptide) and gastric emptying as measured by 13C (carbon 13)-octanoate breath tests. Prior to the meal tests, liraglutide will be administered at a dose of 1.2 mg per injection, which is the recommended dose for treatment. Sitagliptin will be used at a dose of 100 mg, which is recommended for clinical use.
- Conditions
- Type 2 Diabetes
- Being tested
- Placebo, Mixed meal test, Liraglutide, Sitagliptin
- Keywords
- Incretin, DPP-4 inhibitor
- Medical subject headings
- Diabetes Mellitus, Type 2
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PlaceboDrug
Patients administered a single dose of placebo during a mixed meal challenge.
Mixed meal testOther
Subjects will be instructed to consume the mixed meal test within 20 minutes. The exact start and stop time of the mixed meal test consumption will be recorded in the CRF. The mixed meal test procedures will be identical for all subjects randomised in the study. To detect the plasma glucose excursion after mixed meal test, plasma glucose will be closely monitored
LiraglutideDrug
Also called Victoza
Patients on metformin monotherapy will, after screening and randomization, enter a run-in period of 2 weeks with the additional treatment of liraglutide (0.6 mg/d for 1 week followed by 1.2 mg/d for another week) that will be continued for the entire duration of the study.
SitagliptinDrug
Patients administered a single dose of Sitagliptin during a mixed meal challenge.
| Study group | Role | What they receive |
|---|---|---|
| Sitagliptin, then Placebo | Experimental | Not described Receives: Drug: Placebo; Other: Mixed meal test; Drug: Liraglutide; Drug: Sitagliptin |
| Placebo, then Sitagliptin | Experimental | Not described Receives: Drug: Placebo; Other: Mixed meal test; Drug: Liraglutide; Drug: Sitagliptin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incremental Area Under the Plasma Glucose (BG) Concentration-time Profile (AUC)
Incremental area under the plasma glucose (BG) concentration-time profile (AUC) immediately before to 300 min after a mixed meal test. In addition, the time course of BG values will be analysed with an ANCOVA model for repeated measurements with placebo baseline values as covariate. Time points to create the curce were 0, 15, 30, 45, 60, 90, 120, 150, 180, 240 and 300 minutes post mixed meal test.
Measured: 0 to 300 min post mixed meal test
Secondary outcomes (8)
AUC Plasma Glucose
Incremental AUC from 0 to 300 min
Measured: Approximately 6 weeks (range 9 - 60 days / 8.5 weeks)
AUC Insulin
Measured: Approximately 6 weeks (range 9 - 60 days / 8.5 weeks)
AUC C-peptide
Measured: Approximately 6 weeks (range 9 - 60 days / 8.5 weeks)
AUC Glucagon
Measured: Approximately 6 weeks (range 9 - 60 days / 8.5 weeks)
AUC Total GLP-1
Measured: Approximately 6 weeks (range 9 - 60 days / 8.5 weeks)
AUC Total GIP
Measured: Approximately 6 weeks (range 9 - 60 days / 8.5 weeks)
AUC Active GLP-1
Measured: Approximately 6 weeks (range 9 - 60 days / 8.5 weeks)
AUC Active GIP
Measured: Approximately 6 weeks (range 9 - 60 days / 8.5 weeks)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Sep 2013 (estimated)
- Study startAug 2013
- Primary completionApr 2014
- Study completionJun 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Type 2 DiabetesStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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 3
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 16 participants (actual)
Sponsor and investigators
- Lead sponsor
- Michael A. Nauck
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Michael A. Nauck, Diabeteszentrum Bad Lauterberg im Harz
- Investigators
- Michael A. Nauck, Prof. Dr., Principal investigator, Diabeteszentrum Bad Lauterberg
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01937598
- Sponsor's protocol ID
- 120-0569-DZBL-2012
- Other IDs
- 2013-001764-35
- Status last verified
- Dec 2016
- First submitted
- 27 Aug 2013
- Last updated
- 30 Jan 2017
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 30 Jan 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Antidiabetic Effects of Adding a DPP-4 Inhibitor (Sitagliptin) to Pre-Existing Treatment With an Incretin Mimetic (Liraglutide) in Patients With Type 2 Diabetes Treated With Metformin
- ClinicalTrials.gov ID
- NCT01937598
- Acronym / sponsor ID
- 120-0569-DZBL-2012
- Conditions
- Type 2 Diabetes
- Keywords
- Incretin, DPP-4 inhibitor
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 16 participants (actual)
- Lead sponsor
- Michael A. NauckUniversity, hospital or other
- Study start
- Aug 2013
- Primary completion
- Apr 2014 (actual)
- Study completion
- Jun 2015 (actual)
- First posted
- 9 Sep 2013 (estimated)
- Results
- Posted 30 Jan 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Objectives: To quantify differences in control of glycemia (primary objective) and the secretion of endogenous incretin hormones (secondary objective) comparing sitagliptin or placebo added to pre-existing therapy with liraglutide and metformin
Detailed description
This is a double blind, controlled, cross-over comparison of adding sitagliptin (or placebo) to pre-existing metformin+liraglutide therapy. Patients with type 2 diabetes mellitus (T2DM) on pre-existing treatment with metformin (≥ 1500 mg/d) monotherapy or metformin plus liraglutide (1.2 mg/d) will be studied. Patients on metformin monotherapy will, after screening and randomization, enter a run-in period of 2 weeks with the additional treatment of liraglutide (0.6 mg/d for 1 week followed by 1.2 mg/d for another week). At the end of this 2 weeks therapy, a mixed meal challenge will take place, with the assessment of glucose and hormone responses (insulin, C-peptide, glucagon, GLP-1 [glucagon-like peptide-1], GIP (gastric inhibitory peptide) and gastric emptying as measured by 13C (carbon 13)-octanoate breath tests. Prior to the meal tests, liraglutide will be administered at a dose of 1.2 mg per injection, which is the recommended dose for treatment. Sitagliptin will be used at a dose of 100 mg, which is recommended for clinical use.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Sitagliptin, then Placebo | Experimental | Drug: Placebo, Other: Mixed meal test, Drug: Liraglutide, Drug: Sitagliptin |
| Placebo, then Sitagliptin | Experimental | Drug: Placebo, Other: Mixed meal test, Drug: Liraglutide, Drug: Sitagliptin |
Who may qualify
- Ages
- 25 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Signed \& dated written informed consent
- Male \& female subjects with a diagnosis of type 2 diabetes mellitus according to ADA criteria at least 4 months prior to screening
- Medical history without major pathology (with the exception of type 2 diabetes) as judged by the investigator
- On a stable regimen of metformin for at least 1 month and liraglutide 1.2 mg for at least 1 week at the time-point of randomisation.
- Age: 25 - 75 years, both inclusive
Key exclusion criteria (27 listed)
- Subjects with type 1 diabetes, maturity onset diabetes of the young (MODY) or secondary forms of diabetes such as due to pancreatitis
- Current or previous treatment with insulin therapy (except for treatment at diabetes' diagnosis, within a clinical trial, for surgical procedures or during an acute illness, and no insulin administration within the 6 months before screening)
- Treatment with any hypoglycaemic medication other than metformin and liraglutide within one month prior to screening
- Known of diabetic gastroparesis and / or prokinetic therapy
- Subjects that underwent surgery of the upper gastrointestinal tract
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PlaceboPatients administered a single dose of placebo during a mixed meal challenge. | Drug | Placebo, then Sitagliptin, Sitagliptin, then Placebo |
| Mixed meal testSubjects will be instructed to consume the mixed meal test within 20 minutes. The exact start and stop time of the mixed meal test consumption will be recorded in the CRF. The mixed meal test procedures will be identical for all subjects randomised in the study. To detect the plasma glucose excursion after mixed meal test, plasma glucose will be closely monitored | Other | Placebo, then Sitagliptin, Sitagliptin, then Placebo |
| LiraglutideAlso: VictozaPatients on metformin monotherapy will, after screening and randomization, enter a run-in period of 2 weeks with the additional treatment of liraglutide (0.6 mg/d for 1 week followed by 1.2 mg/d for another week) that will be continued for the entire duration of the study. | Drug | Placebo, then Sitagliptin, Sitagliptin, then Placebo |
| SitagliptinPatients administered a single dose of Sitagliptin during a mixed meal challenge. | Drug | Placebo, then Sitagliptin, Sitagliptin, then Placebo |
Primary outcome
Incremental Area Under the Plasma Glucose (BG) Concentration-time Profile (AUC)
Time frame: 0 to 300 min post mixed meal test
Incremental area under the plasma glucose (BG) concentration-time profile (AUC) immediately before to 300 min after a mixed meal test. In addition, the time course of BG values will be analysed with an ANCOVA model for repeated measurements with placebo baseline values as covariate. Time points to create the curce were 0, 15, 30, 45, 60, 90, 120, 150, 180, 240 and 300 minutes post mixed meal test.
8 secondary outcomes
AUC Plasma Glucose
Time frame: Approximately 6 weeks (range 9 - 60 days / 8.5 weeks)
AUC Insulin
Time frame: Approximately 6 weeks (range 9 - 60 days / 8.5 weeks)
AUC C-peptide
Time frame: Approximately 6 weeks (range 9 - 60 days / 8.5 weeks)
AUC Glucagon
Time frame: Approximately 6 weeks (range 9 - 60 days / 8.5 weeks)
AUC Total GLP-1
Time frame: Approximately 6 weeks (range 9 - 60 days / 8.5 weeks)
AUC Total GIP
Time frame: Approximately 6 weeks (range 9 - 60 days / 8.5 weeks)
AUC Active GLP-1
Time frame: Approximately 6 weeks (range 9 - 60 days / 8.5 weeks)
AUC Active GIP
Time frame: Approximately 6 weeks (range 9 - 60 days / 8.5 weeks)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Jan 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Michael A. Nauck, Prof. Dr. principal investigator
Diabeteszentrum Bad Lauterberg
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Mixed meal test, Liraglutide and Sitagliptin in people with Type 2 Diabetes, run by Michael A. Nauck 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 8 inclusion and 27 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 30 Jan 2017. 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. 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 30 Jan 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Incremental Area Under the Plasma Glucose (BG) Concentration-time Profile (AUC) (time frame: 0 to 300 min post mixed meal test). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 30 Jan 2017.