Type 2 DiabetesPhase 3NCT00411411
Long Term Effects of DPP-IV Inhibitor Treatment in Patients With Type 2 Diabetes
A Phase 3 study testing Januvia in people with Type 2 Diabetes, run by University Hospital, Gentofte, Copenhagen at 1 site in Denmark.
Trial summary
We wish to evaluate the effect of long term treatment with a DPP-IV inhibitor on the function of the incretin hormones Hypothesis We hypothesize that that a gradual improvement in metabolic control induced by DPP-IV inhibitor (Januvia®) treatment significantly ameliorates the impaired secretion and potency of GLP-1… Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Type 2 Diabetes
- What is being tested?
- Januvia
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 49 participants
- Where
- 1 siteDenmark
- Study dates
- Feb 2007to Mar 2009
- 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 18 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Type 2 diabetes diagnosed according to and in accordance with the WHO criteria
- Metformin treatment of ≥ 1 gram
- 7,5 % ≤ HbA1c ≤ 10%
- Age > 18
- BMI ≥ 25 kg/m2
- Informed consent
- Contraception, if appropriate
Who cannot join
- Proliferating retinopathy
- Uremia, end stage renal disease, diabetic nephropathy or any other cause of impaired renal function with s-creatinine > 130 µM and/or albuminuria (>300 mg/day)
- Liver disease with ALAT and/or ASAT > 2 x normal value
- Complicated coronary artery disease, NYHA group III and IV
- Positive screening for islet cell auto antibodies and/or GAD-65 auto antibodies
- Occurrence of type 1 diabetes in first degree relatives
Show all 16Show fewer
- Anaemia
- Pregnancy and/or breast feeding
- Treatment with medication affecting insulin secretion
- non-compliance
- Withdrawal criteria
- The subject may withdraw at will at any time
- Pregnancy discovered during the trial
- Severe illness
- Unacceptable side effects
- If self-measured fasting plasma glucose on three consecutive days exceeds 15 mM, the result is repeated in an immediately scheduled visit, and no treatable intercurrent cause for the hyperglycaemia can be found.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Phase 3, Double Blinded, Placebo Controlled Study of the Effects of 12 Weeks DPP-IV Inhibitor Treatment on Secretion and Action of the Incretin Hormones in Patients With Type 2 Diabetes
We wish to evaluate the effect of long term treatment with a DPP-IV inhibitor on the function of the incretin hormones
Hypothesis We hypothesize that that a gradual improvement in metabolic control induced by DPP-IV inhibitor (Januvia®) treatment significantly ameliorates the impaired secretion and potency of GLP-1 and leads to a restoration of the lost action of GIP.
Read the detailed description
Background The incretin effect, primarily mediated by the peptide hormones GIP and GLP-1, is known to be impaired in patients with type 2 diabetes, and characterised by reduced GLP-1 secretion and potency and a lack of responsiveness to the insulinotropic effect of GIP. The cause of this defect remains unknown, but exogenous administration of GLP-1 has shown promising results in attempts to restore the incretin effect. Due to rapid degradation of both incretin hormones by the enzyme dipeptidyl-peptidase IV (DPP-IV), treatment strategies now focus on GLP-1 analogues and prevention of hormone degradation through DPP-IV inhibition.
Hypothesis We hypothesize that that a gradual improvement in metabolic control induced by DPP-IV inhibitor (Januvia®) treatment significantly ameliorates the impaired secretion and potency of GLP-1 and leads to a restoration of the lost action of GIP.
Objective To assess the effect of three months treatment with Januvia®, administered as tablets once daily, on metabolic control in metformin treated patients with type 2 diabetes, measured as increases in incretin hormones and insulin secretion.
Efficacy end points Primary efficacy end point in trial part one is the relative increase in meal-induced total GLP-1 secretion after one and twelve weeks of Januvia® treatment.
Primary efficacy end point in part two is restoration of the insulinotropic effect of GIP, measured as the relative increase in GIP induced amplification of the late phase insulin secretion (AUC) response to glucose after 12 weeks of Januvia® treatment.
Secondary objectives are examination of GLP-2, somatostatin, glucagon, peptide-YY and two glycaemic control parameters (HbA1c and fasting plasma glucose)
Design This is a single centre, randomized, double blinded, placebo controlled trial. The trial consists of two parts, each consisting of three months of inhibitor treatment. In each part, 24 patients, recruited from the Diabetes Outpatient Clinic of Gentofte University Hospital, will be randomized to a treatment supplement of either Januvia® or placebo.
Procedures During the trial, patients will be tested with well established procedures. In part one, patients will undergo a standardized meal test and two β-cell secretory capacity tests. In part two, patients will undergo standardized hyperglycaemic GIP, GLP-1 and saline clamps.
Safety The trial has a short time span of only three months. With more than ten visits during this time and regular blood sampling, the patients are well monitored.
- Conditions
- Type 2 Diabetes
- Being tested
- Januvia, Placebo
- Keywords
- GLP-1, GIP, Incretin hormones, DPP-IV inhibitor, Hyperglycaemic clamp, Meal test
- 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.
JanuviaDrug
Also called Sitagliptin
200 mg t.i.d
PlaceboDrug
Placebo
| Study group | Role | What they receive |
|---|---|---|
| Placebo | Placebo comparator | Placebo treatment, administered as tablets. Receives: Drug: Placebo |
| Januvia | Experimental | Active treatment Receives: Drug: Januvia |
What is being measured
The primary outcome is the main question the study is designed to answer.
the Relative Increase in Meal-induced Total GLP-1 Secretion
Patients will be followed for 12 weeks with three meal test examinations; before treatment, after 1 week of treatment and after 12 weeks of treatment. Primary outcome is AUC GLP-1 (pM x 120 as stated).
Measured: 12 weeks
Restoration of the Insulinotropic Effect of GIP
Restoration of the insulinotropic effect of GIP measured as the relative increase in GIP induced amplification of the late phase insulin secretion (AUC) response to glucose. Patients will be followed for 12 weeks with examinations after 1 and after 12 weeks of treatment.
Measured: 12 weeks
Secondary outcomes (1)
Examination of GLP-2, Somatostatin, Glucagon, Peptide-YY and Two Glycaemic Control Parameters (HbA1c and Fasting Plasma Glucose)
Secondary objectives are examination of GLP-2, somatostatin, glucagon, peptide-YY and two glycaemic control parameters (HbA1c and fasting plasma glucose). Patients will be followed for 12 weeks with three examinations; before, during and after the treatment
Measured: 12 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Dec 2006 (estimated)
- Study startFeb 2007
- Primary completionFeb 2009
- Study completionMar 2009
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.
- Publications (1)Papers the sponsor has linked to this study.
- 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
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 49 participants (actual)
Sponsor and investigators
- Lead sponsor
- University Hospital, Gentofte, Copenhagen
- Sponsor type
- University, hospital or other
- Collaborators
- Merck Sharp & Dohme LLC
- Responsible party
- Principal investigator, Kasper Aaboe, University Hospital, Gentofte, Copenhagen
- Investigators
- Kasper Aaboe, MD, Principal investigator, Gentofte University Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00411411
- Sponsor's protocol ID
- 1502
- Status last verified
- Jul 2014
- First submitted
- 13 Dec 2006
- Last updated
- 13 Aug 2014
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Aaboe K, Akram S, Deacon CF, Holst JJ, Madsbad S, Krarup T. Restoration of the insulinotropic effect of glucose-dependent insulinotropic polypeptide contributes to the antidiabetic effect of dipeptidyl peptidase-4 inhibitors. Diabetes Obes Metab. 2015 Jan;17(1):74-81. doi: 10.1111/dom.12395. Epub 2014 Oct 26.
PubMed 25243647
Study at a glance
From the registry record, last updated by the sponsor on 13 Aug 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase 3, Double Blinded, Placebo Controlled Study of the Effects of 12 Weeks DPP-IV Inhibitor Treatment on Secretion and Action of the Incretin Hormones in Patients With Type 2 Diabetes
- ClinicalTrials.gov ID
- NCT00411411
- Acronym / sponsor ID
- 1502
- Conditions
- Type 2 Diabetes
- Keywords
- GLP-1, GIP, Incretin hormones, DPP-IV inhibitor, Hyperglycaemic clamp, Meal test
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 49 participants (actual)
- Lead sponsor
- University Hospital, Gentofte, CopenhagenUniversity, hospital or other
- Collaborators
- Merck Sharp & Dohme LLC
- Study start
- Feb 2007
- Primary completion
- Feb 2009 (actual)
- Study completion
- Mar 2009 (actual)
- First posted
- 14 Dec 2006 (estimated)
- Results
- Posted 13 Aug 2014
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
We wish to evaluate the effect of long term treatment with a DPP-IV inhibitor on the function of the incretin hormones
Hypothesis We hypothesize that that a gradual improvement in metabolic control induced by DPP-IV inhibitor (Januvia®) treatment significantly ameliorates the impaired secretion and potency of GLP-1 and leads to a restoration of the lost action of GIP.
Detailed description
Background The incretin effect, primarily mediated by the peptide hormones GIP and GLP-1, is known to be impaired in patients with type 2 diabetes, and characterised by reduced GLP-1 secretion and potency and a lack of responsiveness to the insulinotropic effect of GIP. The cause of this defect remains unknown, but exogenous administration of GLP-1 has shown promising results in attempts to restore the incretin effect. Due to rapid degradation of both incretin hormones by the enzyme dipeptidyl-peptidase IV (DPP-IV), treatment strategies now focus on GLP-1 analogues and prevention of hormone degradation through DPP-IV inhibition.
Hypothesis We hypothesize that that a gradual improvement in metabolic control induced by DPP-IV inhibitor (Januvia®) treatment significantly ameliorates the impaired secretion and potency of GLP-1 and leads to a restoration of the lost action of GIP.
Objective To assess the effect of three months treatment with Januvia®, administered as tablets once daily, on metabolic control in metformin treated patients with type 2 diabetes, measured as increases in incretin hormones and insulin secretion.
Efficacy end points Primary efficacy end point in trial part one is the relative increase in meal-induced total GLP-1 secretion after one and twelve weeks of Januvia® treatment.
Primary efficacy end point in part two is restoration of the insulinotropic effect of GIP, measured as the relative increase in GIP induced amplification of the late phase insulin secretion (AUC) response to glucose after 12 weeks of Januvia® treatment.
Secondary objectives are examination of GLP-2, somatostatin, glucagon, peptide-YY and two glycaemic control parameters (HbA1c and fasting plasma glucose)
Design This is a single centre, randomized, double blinded, placebo controlled trial. The trial consists of two parts, each consisting of three months of inhibitor treatment. In each part, 24 patients, recruited from the Diabetes Outpatient Clinic of Gentofte University Hospital, will be randomized to a treatment supplement of either Januvia® or placebo.
Procedures During the trial, patients will be tested with well established procedures. In part one, patients will undergo a standardized meal test and two β-cell secretory capacity tests. In part two, patients will undergo standardized hyperglycaemic GIP, GLP-1 and saline clamps.
Safety The trial has a short time span of only three months. With more than ten visits during this time and regular blood sampling, the patients are well monitored.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Placebo | Placebo comparator | Drug: PlaceboPlacebo treatment, administered as tablets. |
| Januvia | Experimental | Drug: JanuviaActive treatment |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Type 2 diabetes diagnosed according to and in accordance with the WHO criteria
- Metformin treatment of ≥ 1 gram
- 7,5 % ≤ HbA1c ≤ 10%
- Age > 18
- BMI ≥ 25 kg/m2
Key exclusion criteria (16 listed)
- Proliferating retinopathy
- Uremia, end stage renal disease, diabetic nephropathy or any other cause of impaired renal function with s-creatinine > 130 µM and/or albuminuria (>300 mg/day)
- Liver disease with ALAT and/or ASAT > 2 x normal value
- Complicated coronary artery disease, NYHA group III and IV
- Positive screening for islet cell auto antibodies and/or GAD-65 auto antibodies
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 |
|---|---|---|
| JanuviaAlso: Sitagliptin200 mg t.i.d | Drug | Januvia |
| PlaceboPlacebo | Drug | Placebo |
Primary outcome
the Relative Increase in Meal-induced Total GLP-1 Secretion
Time frame: 12 weeks
Patients will be followed for 12 weeks with three meal test examinations; before treatment, after 1 week of treatment and after 12 weeks of treatment. Primary outcome is AUC GLP-1 (pM x 120 as stated).
Restoration of the Insulinotropic Effect of GIP
Time frame: 12 weeks
Restoration of the insulinotropic effect of GIP measured as the relative increase in GIP induced amplification of the late phase insulin secretion (AUC) response to glucose. Patients will be followed for 12 weeks with examinations after 1 and after 12 weeks of treatment.
1 secondary outcome
Examination of GLP-2, Somatostatin, Glucagon, Peptide-YY and Two Glycaemic Control Parameters (HbA1c and Fasting Plasma Glucose)
Time frame: 12 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Aug 2014.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 25243647Aaboe K, Akram S, Deacon CF, Holst JJ, Madsbad S, Krarup T. Restoration of the insulinotropic effect of glucose-dependent insulinotropic polypeptide contributes to the antidiabetic effect of dipeptidyl peptidase-4 inhibitors. Diabetes Obes Metab. 2015 Jan;17(1):74-81. doi: 10.1111/dom.12395. Epub 2014 Oct 26.
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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.
Kasper Aaboe, MD principal investigator
Gentofte University Hospital
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 Januvia in people with Type 2 Diabetes, run by University Hospital, Gentofte, Copenhagen at 1 site in Denmark.
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 7 inclusion and 16 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 13 Aug 2014. 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 Denmark. 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 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 13 Aug 2014). 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?
the Relative Increase in Meal-induced Total GLP-1 Secretion (time frame: 12 weeks). The study lists 2 primary outcomes in all. 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 NCT00411411, which also lists 1 linked publication.
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 13 Aug 2014.