Diabetes Mellitus, Type 2Phase 1NCT01703286

Trial to Assess the Influence of 4 Weeks' Treatment With Linagliptin as Compared to Glimepiride and Placebo on Endothelial Function in Patients With Type 2 Diabetes Using FMD (Flow-Mediated Vasodilation)

A Phase 1 study testing Linagliptin and Glimepiride in people with Diabetes Mellitus, Type 2, run by Boehringer Ingelheim 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 general aim of the present study is to investigate the impact of 4 weeks treatment with linagliptin (5 mg) on endothelial function in patients with type 2 diabetes mellitus. In the current trial this effect of linagliptin treatment on endothelial function will be compared against both the sulfonylurea glimepiride… Read more about this study

Who is it for?: Ages 18 to 65 years
Conditions the study is for: Diabetes Mellitus, Type 2
What is being tested?: Linagliptin and Glimepiride
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 42 participants
Where: 1 siteGermany
Study dates: Oct 2012to Jan 2014
Phase: Phase 1
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 65 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

Type 2 diabetic male and female patients according to the following criteria:
Based upon a complete medical history and clinical laboratory tests
Age >= 18 and Age <= 65 years
Body mass index >= 25 <= 35 kg/m2
HbA1c <= 7.5%
Treatment with metformin (=1500 mg daily) for <= 3 months

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Signed and dated written informed consent prior to admission to the study in accordance with GCP and the local legislation.
For female patients of childbearing potential:
Use of acceptable method of contraception (Pearl-Index <1).

Who cannot join

Treatment with any glucose-lowering drug except for metformin within prior 3 months.
Any finding of the medical examination (including blood pressure, pulse rate and electrocardiogram) deviating from normal and of clinical relevance.
Any evidence of a clinically relevant acute concomitant disease
History of cardiovascular disease (e.g. coronary artery disease history of acute myocard infarction or stroke, peripheral vascular disease).
History of major diabetic complications (e.g. nephropathy, retinopathy)
Gastrointestinal, hepatic, renal, respiratory, cardiovascular, immunological or hormonal disorders (except: hypertension treated with angiotensin receptor blocker or angiotensin-converting-enzyme inhibitors, hyperlipidemia with statin therapy, thyroid hormone replacement therapy, all stable for at least three months prior to screening).

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Surgery of the gastrointestinal tract (except appendectomy).
Diseases of the central nervous system (such as epilepsy) or psychiatric disorders or neurological disorders.
History of relevant orthostatic hypotension, fainting spells or blackouts.
Chronic or relevant acute infections.
History of relevant allergy/hypersensitivity (including allergy to drug or its excipients).
Intake of drugs with a long half-life (> 24 hours) within at least one month or less than 10 half-lives of the respective drug prior to administration or during the trial.
Participation in another trial with an investigational drug within one month prior to administration or during the trial.
Smoker (>= 1 cigarettes or >= 1 cigars or >= 1 pipes/day).
Alcohol abuse (more than 60 g/day).
Drug abuse.
Blood donation (more than 100 mL within four weeks prior to administration or during the trial).
Excessive physical activities (within one week prior to administration or during the trial).
Any laboratory value outside the reference range that is of clinical relevance.

Trial locations and contacts

1 site in 1 country.

Germany1 site

1218.105.001 Boehringer Ingelheim Investigational Site
Neuss

Other trials in Germany

About this study

Official title: Randomized, Three Period Cross Over, Double Blind, Double Dummy Study in Type 2 Diabetic Patients to Assess the Endothelial Effects of Linagliptin, Glimepiride and Placebo Therapy for 28 Days ('ENDOTHELINA')

Besides placebo, glimepiride was chosen as a comparator, as it is one compound of the second most used oral antidiabetic drug class.

Conditions: Diabetes Mellitus, Type 2
Being tested: Placebo, Linagliptin, Glimepiride
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
Placebo matching Glimepiride
LinagliptinDrug
given once daily for 28 days
PlaceboDrug
Placebo matching Linagliptin
PlaceboDrug
Placebo matching Linagliptin
PlaceboDrug
Placebo matching Glimepiride
GlimepirideDrug
1 mg for 7 days followed by uptitration to 2 mg (given for following 21 days)

Study groups in NCT01703286
Study group	Role	What they receive
Linagliptin 5mg	Experimental	given once daily over 28 days Receives: Drug: Placebo; Drug: Linagliptin
Glimepiride	Active comparator	given once daily in 1mg dosis over 7 days, following a titration step to 2mg and application for 21 days Receives: Drug: Placebo; Drug: Glimepiride
Placebo	Placebo comparator	given once daily over 28 days Receives: Drug: Placebo

What is being measured

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

Change From Baseline in Flow Mediated Vasodilation (FMD) Under Fasted Condition on Day 28
Endothelial function under fasted condition was measured with flow mediated vasodilation (FMD). The change from baseline was calculated as the value on Day 28 divided by the respective value at baseline.
Measured: baseline and day 28 for each treatment arm

Secondary outcomes (3)

Change From Baseline in Flow Mediated Vasodilation (FMD) 2 h Post Meal on Day 28
Endothelial function 2 hours post meal was measured with flow mediated vasodilation (FMD). The change from baseline was calculated as the value on Day 28 divided by the respective value at baseline.
Measured: baseline and day 28 for each treatment arm
Change From Baseline in 2 Hours Post Meal Endothelial Independent Vasodilation (EIDV) on Day 28
Endothelial function 2h post-meal was measured by endothelial independent vasodilation (EIDV). The change from baseline was calculated as the value on Day 28 divided by the respective value at baseline.
Measured: baseline and day 28 for each treatment arm
Number of Patients With Adverse Events
Number of patients with any adverse events
Measured: up to 20 weeks

Timeline

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

Oct 2012Jan 2014

First posted10 Oct 2012 (estimated)
Study startOct 2012
Primary completionJan 2014
Study completionJan 2014

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 Diabetes Mellitus, Type 2Studies of the same condition, open and under way.
More trials run by Boehringer IngelheimThe sponsor's other registered studies.
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 1
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Crossover
Masking: Double blind
Enrolment: 42 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01703286
Sponsor's protocol ID: 1218.105
Other IDs: 2012-003317-33
Status last verified: Jan 2015
First submitted: 1 Oct 2012
Last updated: 19 Jan 2015
Results posted: Yes, on ClinicalTrials.gov

Publications

Jax T, Stirban A, Terjung A, Esmaeili H, Berk A, Thiemann S, Chilton R, von Eynatten M, Marx N. A randomised, active- and placebo-controlled, three-period crossover trial to investigate short-term effects of the dipeptidyl peptidase-4 inhibitor linagliptin on macro- and microvascular endothelial function in type 2 diabetes. Cardiovasc Diabetol. 2017 Jan 21;16(1):13. doi: 10.1186/s12933-016-0493-3.
PubMed 28109295

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

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Study at a glance

From the registry record, last updated by the sponsor on 19 Jan 2015. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Randomized, Three Period Cross Over, Double Blind, Double Dummy Study in Type 2 Diabetic Patients to Assess the Endothelial Effects of Linagliptin, Glimepiride and Placebo Therapy for 28 Days ('ENDOTHELINA')
ClinicalTrials.gov ID: NCT01703286
Acronym / sponsor ID: 1218.105
Conditions: Diabetes Mellitus, Type 2
Phase: Phase 1
Study type: Interventional
Recruitment status: Completed
Enrolment: 42 participants (actual)
Lead sponsor: Boehringer IngelheimIndustry (pharma, biotech, devices)
Collaborators: Eli Lilly and Company
Study start: Oct 2012
Primary completion: Jan 2014 (actual)
Study completion: Jan 2014 (actual)
First posted: 10 Oct 2012 (estimated)
Results: Posted 19 Jan 2015

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Besides placebo, glimepiride was chosen as a comparator, as it is one compound of the second most used oral antidiabetic drug class.

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Crossover
Masking: Double blind
Number of arms: 3

Arm	Type	Receives
Linagliptin 5mg	Experimental	Drug: Placebo, Drug: Linagliptingiven once daily over 28 days
Glimepiride	Active comparator	Drug: Placebo, Drug: Glimepiridegiven once daily in 1mg dosis over 7 days, following a titration step to 2mg and application for 21 days
Placebo	Placebo comparator	Drug: Placebogiven once daily over 28 days

Who may qualify

Ages: 18 to 65 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (9 listed)

Type 2 diabetic male and female patients according to the following criteria:
Based upon a complete medical history and clinical laboratory tests
Age >= 18 and Age <= 65 years
Body mass index >= 25 <= 35 kg/m2
HbA1c <= 7.5%

Key exclusion criteria (19 listed)

Treatment with any glucose-lowering drug except for metformin within prior 3 months.
Any finding of the medical examination (including blood pressure, pulse rate and electrocardiogram) deviating from normal and of clinical relevance.
Any evidence of a clinically relevant acute concomitant disease
History of cardiovascular disease (e.g. coronary artery disease history of acute myocard infarction or stroke, peripheral vascular disease).
History of major diabetic complications (e.g. nephropathy, retinopathy)

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
PlaceboPlacebo matching Glimepiride	Drug	Linagliptin 5mg
Linagliptingiven once daily for 28 days	Drug	Linagliptin 5mg
PlaceboPlacebo matching Linagliptin	Drug	Glimepiride
PlaceboPlacebo matching Linagliptin	Drug	Placebo
PlaceboPlacebo matching Glimepiride	Drug	Placebo
Glimepiride1 mg for 7 days followed by uptitration to 2 mg (given for following 21 days)	Drug	Glimepiride

Primary outcome

Change From Baseline in Flow Mediated Vasodilation (FMD) Under Fasted Condition on Day 28
Time frame: baseline and day 28 for each treatment arm
Endothelial function under fasted condition was measured with flow mediated vasodilation (FMD). The change from baseline was calculated as the value on Day 28 divided by the respective value at baseline.

3 secondary outcomes

Change From Baseline in Flow Mediated Vasodilation (FMD) 2 h Post Meal on Day 28
Time frame: baseline and day 28 for each treatment arm
Change From Baseline in 2 Hours Post Meal Endothelial Independent Vasodilation (EIDV) on Day 28
Time frame: baseline and day 28 for each treatment arm
Number of Patients With Adverse Events
Time frame: up to 20 weeks

Results and safety

Results posted to the registry on 19 Jan 2015, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Pbo/ G1-4/ L 5	7	7
L 5/ G 1-4/ Pbo	7	7
G 1-4/ L 5/ Pbo	7	7
G1-4/ Pbo/ L 5	7	6
Pbo/ L 5/ G1-4	7	7
L 5/ Pbo/ G1-4/	7	6

Primary outcome: Change From Baseline in Flow Mediated Vasodilation (FMD) Under Fasted Condition on Day 28

Time frame: baseline and day 28 for each treatment arm. Geometric mean (90% Confidence Interval). Unit: percentage

Measure	Linagliptin 5 mg n = 39	Glimepiride 1-4 mg n = 41	Placebo n = 39
Value	0.885 (0.695 to 1.128)	1.002 (0.795 to 1.262)	1.002 (0.786 to 1.277)

Linagliptin 5 mg vs Glimepiride 1-4 mg: Geometric mean ratio (net): 0.884 (90% CI 0.633 to 1.235), p = 0.5403, ANOVA
Linagliptin 5 mg vs Placebo: Geometric mean ratio (net): 0.884 (90% CI 0.632 to 1.235), p = 0.5402, ANOVA
Glimepiride 1-4 mg vs Placebo: Geometric mean ratio (net): 1.000 (90% CI 0.715 to 1.397), p = 0.9989, ANOVA

Population analysed: Efficacy set (ES)- included all patients of the TS who provided at least 1 observation for at least 1 primary, secondary, or other efficacy endpoint without important protocol violations relevant for the statistical evaluation of these endpoints.

3 secondary outcomes are reported in the full results.

Adverse events

Time frame: 28 days treatment period + 7 days residual effect period. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Linagliptin 5 mg	0 of 40 (0%)	6 of 40 (15%)	Not reported
Glimepiride 1-4 mg	0 of 41 (0%)	20 of 41 (48.8%)	Not reported
Placebo	0 of 40 (0%)	9 of 40 (22.5%)	Not reported

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 19 Jan 2015.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 28109295Jax T, Stirban A, Terjung A, Esmaeili H, Berk A, Thiemann S, Chilton R, von Eynatten M, Marx N. A randomised, active- and placebo-controlled, three-period crossover trial to investigate short-term effects of the dipeptidyl peptidase-4 inhibitor linagliptin on macro- and microvascular endothelial function in type 2 diabetes. Cardiovasc Diabetol. 2017 Jan 21;16(1):13. doi: 10.1186/s12933-016-0493-3.
Related InfoLink provided by the sponsor.

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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.

Boehringer Ingelheim study chair

Boehringer Ingelheim

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Linagliptin and Glimepiride in people with Diabetes Mellitus, Type 2, run by Boehringer Ingelheim 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 9 inclusion and 19 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 19 Jan 2015. 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?

Yes. Results are posted in the registry (first posted 19 Jan 2015). 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?

Change From Baseline in Flow Mediated Vasodilation (FMD) Under Fasted Condition on Day 28 (time frame: baseline and day 28 for each treatment arm). 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 NCT01703286, 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 19 Jan 2015.