Arterial HypertensionPhase 3NCT02376075
Effects of Linagliptin on Endothelial- , Renal-, and Retinal Function in Patients With Hypertension and Albuminuria
A Phase 3 study testing Linagliptin in people with Arterial Hypertension and Albuminuria, run by ikfe-CRO GmbH at 1 site in Germany.
Trial summary
A recent study with the DPP-IV inhibitor Linagliptin showed an improvement in the urinary albumin creatinine ratio in patients with diabetic nephropathy. Gutzwiller et. Al. have shown that GLP-1 increases renal Na secretion and inhibits renal H secretion, further indicating some direct renal effects of GLP-1. Read more about this study
- Who is it for?
- Ages 45 to 80 years
- Conditions the study is for
- Arterial Hypertension, Albuminuria
- What is being tested?
- Linagliptin
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 43 participants
- Where
- 1 siteGermany
- Study dates
- Jan 2013to Sep 2014
- Phase
- Phase 3
- 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 45 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patient has signed and dated written informed consent to participate in the trial
- Arterial hypertension
- Stable antihypertensive treatment within the last 3 months
- Age ≥ 45 - ≤ 80 years
- Micro- or macroalbuminuria defined as UACR in morning urine > 20 mg/g in female and > 30 mg/g in male and/or arterial hypertension for more than 5 years currently treated with two or more antihypertensive drugs to control blood pressure and a history of cardiovascular disease or stroke.
- Patient consents that his/her family physician will be informed of trial participation
Who cannot join
- History of type 1 diabetes
- History of type 2 diabetes
- Uncontrolled hypertension (systolic blood pressure >180 mmHg and/or diastolic blood pressure >100 mmHg)
- Acute infections
- Any history of glomerulonephritis
- Any kidney disease not caused by hypertension as judged by the Investigator
Show all 24Show fewer
- Glomerular filtration rate (GFR) < 30 ml/min (estimated by use of the Modification of Diet in Renal Disease (MDRD) formula)
- Medical history of hypersensitivity to the study drugs or to drugs with similar chemical structures
- History of severe or multiple allergies
- Treatment with any other investigational drug within 3 months before trial entry
- Progressive fatal disease
- History of drug or alcohol abuse in the past 2 years
- Condition after kidney transplantation
- Serum potassium > 5.5 mmol/L
- Pregnancy or breast feeding
- Sexually active woman of childbearing age not practicing a highly effective method of birth control as defined as those which result in a low failure rate (i.e. less than 1% per year) when used consistently and correctly such as implants, injectables, combined oral contraceptives, hormonal IUDs, sexual abstinence or vasectomised partner.
- Acute myocardial infarction, open heart surgery or cerebral event (stroke/TIA) within the previous 3 months
- Any elective surgery during study participation
- Uncontrolled unstable angina pectoris
- Intake of Coumarin or coumarin derived compounds such as phenprocoumon (Marcumar) or warfarin (Coumadin, Warfant)
- Intake of rifampicin or carbamazepine
- HbA1c ≥ 6,5%
- A Body Mass Index of > 35 kg/m²
- CHF NYHA stage III - IV
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Effects of Linagliptin on Endothelial- , Renal-, and Retinal Function in Comparison to Placebo in Patients With Hypertension and Albuminuria
A recent study with the DPP-IV inhibitor Linagliptin showed an improvement in the urinary albumin creatinine ratio in patients with diabetic nephropathy. Gutzwiller et. Al. have shown that GLP-1 increases renal Na secretion and inhibits renal H secretion, further indicating some direct renal effects of GLP-1.
Therefore, it seems likely that treatment with the DPP-IV inhibitor Linagliptin evolves several beneficial effects on microvascular and endothelial function beyond glucose control which most probably have an impact on the progression of renal and retinal microvascular disease.
The objective of this trial is to investigate the effect of Linagliptin in comparison to placebo on the UACR in patients with high blood pressure and an increased albumin excretion. Numerous, equivalent endothelial, renal, and retinal parameters serve as objectives of the study. All study parameters will be handled in an exploratory sense for the generation of models to further discuss the role of DPP-IV inhibition on renal and retinal physiology.
Read the detailed description
Renal tissue damage and an increase in the albumin excretion rate is a strong predictor for the development and progression of endothelial dysfunction and the development of microvascular and/or macrovascular complications. Increased blood pressure as well as increased glucose levels were found to impair renal- and retinal function, and a close association in the incidence and progression rate of retinopathy and nephropathy could be observed. Endothelial dysfunction and alterations in microvascular blood flow are early pathogenetic features in the development of renal and retinal tissue damage as found in patients with arterial hypertension and / or diabetes mellitus. A couple of studies have shown that urinary albumin excretion is associated with morphological and functional alterations in retinal microvascular blood flow. In patients with arterial hypertension blood pressure lowering treatment were shown to decrease the albumin excretion rate and to improve endothelial function of the retinal vasculature.
Recently DPP-IV Inhibitors have been introduced in the treatment of type 2 diabetes mellitus. Beside the metabolic effects of this drug class, several pleiotropic effects beyond metabolic control were documented in numerous studies, and are the topic of ongoing clinical research. Treatment with DPP-IV inhibitors was found to improve myocardial and endothelial function, to improve blood lipids, to lower blood pressure and to improve markers of renal function. GLP-1 receptors in vessels, kidney and the heart might account for those glucose independent effects of GLP-1. However, it is also conceivable that DPP-IV inhibition might exert vascular effects independent from GLP-1. In vitro studies demonstrated that DPP-IV is expressed in endothelial cells, and the inhibition of DPP-IV reduced the microvascular tone through direct mediation of the nitric oxide system. Therefore, it seems conceivable that the glucose independent effects of DPP-IV inhibition might be mediated through GLP-1 receptor signaling and /or direct inhibition of the enzyme DPP-IV in vascular, renal, or retinal cells.
A recent study with the DPP-IV inhibitor Linagliptin showed an improvement in the urinary albumin creatinine ratio in patients with diabetic nephropathy. Gutzwiller et. Al. have shown that GLP-1 increases renal Na secretion and inhibits renal H secretion, further indicating some direct renal effects of GLP-1.
Therefore, it seems likely that treatment with the DPP-IV inhibitor Linagliptin evolves several beneficial effects on microvascular and endothelial function beyond glucose control which most probably have an impact on the progression of renal and retinal microvascular disease.
The objective of this trial is to investigate the effect of Linagliptin in comparison to placebo on the UACR in patients with high blood pressure and an increased albumin excretion. Numerous, equivalent endothelial, renal, and retinal parameters serve as objectives of the study. All study parameters will be handled in an exploratory sense for the generation of models to further discuss the role of DPP-IV inhibition on renal and retinal physiology.
- Conditions
- Arterial Hypertension, Albuminuria
- Being tested
- Linagliptin, Placebo
- Medical subject headings
- Hypertension, Albuminuria
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
LinagliptinDrug
Also called Trajenta
Intake of tablets containing 5 mg Linagliptin, administered once daily as add on to pre-existing antihypertensive treatment for 6 weeks
PlaceboDrug
Intake of Placebo, administered once daily as add on to pre-existing antihypertensive treatment for 6 weeks
| Study group | Role | What they receive |
|---|---|---|
| Placebo | Placebo comparator | Placebo, tablets, administered once daily as add on to pre-existing antihypertensive treatment Receives: Drug: Placebo |
| Linagliptin | Active comparator | Linagliptin, tablets containing 5 mg, administered once daily as add on to pre-existing antihypertensive treatment Receives: Drug: Linagliptin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Albumin/Creatinine Ratio (UACR) in 24h urine change between Baseline and Visit 4
Measured: up to 14 weeks of study drug intake
Secondary outcomes (12)
24 hour urinary sodium excretion change between Baseline and Visit 4
Measured: after 14 weeks of study drug intake
Fasting cystatin C change between Baseline and V4
Measured: up to 14 weeks of study drug intake
Fasting cGMP change between Baseline and Visit 4
Measured: after 14 weeks of study drug intake
Fasting serum ADMA change between Baseline and V4
Measured: up to 14 weeks of study drug intake
Fasting hsCRP change between Baseline and Visit 4
Measured: up to 14 weeks of study drug intake
Fasting TGF-ß1 change between Baseline and Visit 4
Measured: after 14 weeks of study drug intake
Retinal endothelial function change between Baseline and Visit 4
Measured: up to 14 weeks of study drug intake
Retinal microvascular blood flow change between Baseline and Visit 4
Measured: up to 14 weeks of study drug intake
24h blood pressure measurements change between Baseline and Visit 4
Measured: up to 14 weeks of study drug intake
HbA1c change between Baseline and Visit 4
Measured: up to 14 weeks of study drug intake
Body weight change during study participation
Measured: up to 14 weeks of study drug intake
Adverse events during study participation
Measured: up to 14 weeks of study drug intake
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Mar 2015 (estimated)
- Study startJan 2013
- Primary completionSep 2014
- Study completionSep 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Arterial HypertensionStudies 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
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Outcomes assessor
- Enrolment
- 43 participants (actual)
Sponsor and investigators
- Lead sponsor
- ikfe-CRO GmbH
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Ikfe GmbH, MLM Medical Labs GmbH
- Responsible party
- Sponsor
- Investigators
- Thomas Forst, MD, PhD, Principal investigator, Profil GmbH Mainz
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02376075
- Sponsor's protocol ID
- ikfe-Lina-003
- Other IDs
- 2012-004300-35
- Status last verified
- Feb 2015
- First submitted
- 11 Feb 2015
- Last updated
- 3 Mar 2015
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 3 Mar 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effects of Linagliptin on Endothelial- , Renal-, and Retinal Function in Comparison to Placebo in Patients With Hypertension and Albuminuria
- ClinicalTrials.gov ID
- NCT02376075
- Acronym / sponsor ID
- ikfe-Lina-003
- Conditions
- Arterial Hypertension, Albuminuria
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 43 participants (actual)
- Lead sponsor
- ikfe-CRO GmbHIndustry (pharma, biotech, devices)
- Collaborators
- Ikfe GmbH, MLM Medical Labs GmbH
- Study start
- Jan 2013
- Primary completion
- Sep 2014 (actual)
- Study completion
- Sep 2014 (actual)
- First posted
- 3 Mar 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
A recent study with the DPP-IV inhibitor Linagliptin showed an improvement in the urinary albumin creatinine ratio in patients with diabetic nephropathy. Gutzwiller et. Al. have shown that GLP-1 increases renal Na secretion and inhibits renal H secretion, further indicating some direct renal effects of GLP-1.
Therefore, it seems likely that treatment with the DPP-IV inhibitor Linagliptin evolves several beneficial effects on microvascular and endothelial function beyond glucose control which most probably have an impact on the progression of renal and retinal microvascular disease.
The objective of this trial is to investigate the effect of Linagliptin in comparison to placebo on the UACR in patients with high blood pressure and an increased albumin excretion. Numerous, equivalent endothelial, renal, and retinal parameters serve as objectives of the study. All study parameters will be handled in an exploratory sense for the generation of models to further discuss the role of DPP-IV inhibition on renal and retinal physiology.
Detailed description
Renal tissue damage and an increase in the albumin excretion rate is a strong predictor for the development and progression of endothelial dysfunction and the development of microvascular and/or macrovascular complications. Increased blood pressure as well as increased glucose levels were found to impair renal- and retinal function, and a close association in the incidence and progression rate of retinopathy and nephropathy could be observed. Endothelial dysfunction and alterations in microvascular blood flow are early pathogenetic features in the development of renal and retinal tissue damage as found in patients with arterial hypertension and / or diabetes mellitus. A couple of studies have shown that urinary albumin excretion is associated with morphological and functional alterations in retinal microvascular blood flow. In patients with arterial hypertension blood pressure lowering treatment were shown to decrease the albumin excretion rate and to improve endothelial function of the retinal vasculature.
Recently DPP-IV Inhibitors have been introduced in the treatment of type 2 diabetes mellitus. Beside the metabolic effects of this drug class, several pleiotropic effects beyond metabolic control were documented in numerous studies, and are the topic of ongoing clinical research. Treatment with DPP-IV inhibitors was found to improve myocardial and endothelial function, to improve blood lipids, to lower blood pressure and to improve markers of renal function. GLP-1 receptors in vessels, kidney and the heart might account for those glucose independent effects of GLP-1. However, it is also conceivable that DPP-IV inhibition might exert vascular effects independent from GLP-1. In vitro studies demonstrated that DPP-IV is expressed in endothelial cells, and the inhibition of DPP-IV reduced the microvascular tone through direct mediation of the nitric oxide system. Therefore, it seems conceivable that the glucose independent effects of DPP-IV inhibition might be mediated through GLP-1 receptor signaling and /or direct inhibition of the enzyme DPP-IV in vascular, renal, or retinal cells.
A recent study with the DPP-IV inhibitor Linagliptin showed an improvement in the urinary albumin creatinine ratio in patients with diabetic nephropathy. Gutzwiller et. Al. have shown that GLP-1 increases renal Na secretion and inhibits renal H secretion, further indicating some direct renal effects of GLP-1.
Therefore, it seems likely that treatment with the DPP-IV inhibitor Linagliptin evolves several beneficial effects on microvascular and endothelial function beyond glucose control which most probably have an impact on the progression of renal and retinal microvascular disease.
The objective of this trial is to investigate the effect of Linagliptin in comparison to placebo on the UACR in patients with high blood pressure and an increased albumin excretion. Numerous, equivalent endothelial, renal, and retinal parameters serve as objectives of the study. All study parameters will be handled in an exploratory sense for the generation of models to further discuss the role of DPP-IV inhibition on renal and retinal physiology.
Study design
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Placebo | Placebo comparator | Drug: PlaceboPlacebo, tablets, administered once daily as add on to pre-existing antihypertensive treatment |
| Linagliptin | Active comparator | Drug: LinagliptinLinagliptin, tablets containing 5 mg, administered once daily as add on to pre-existing antihypertensive treatment |
Who may qualify
- Ages
- 45 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Patient has signed and dated written informed consent to participate in the trial
- Arterial hypertension
- Stable antihypertensive treatment within the last 3 months
- Age ≥ 45 - ≤ 80 years
- Micro- or macroalbuminuria defined as UACR in morning urine > 20 mg/g in female and > 30 mg/g in male and/or arterial hypertension for more than 5 years currently treated with two or more antihypertensive drugs to control blood pressure and a history of cardiovascular disease or stroke.
Key exclusion criteria (24 listed)
- History of type 1 diabetes
- History of type 2 diabetes
- Uncontrolled hypertension (systolic blood pressure >180 mmHg and/or diastolic blood pressure >100 mmHg)
- Acute infections
- Any history of glomerulonephritis
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 |
|---|---|---|
| LinagliptinAlso: TrajentaIntake of tablets containing 5 mg Linagliptin, administered once daily as add on to pre-existing antihypertensive treatment for 6 weeks | Drug | Linagliptin |
| PlaceboIntake of Placebo, administered once daily as add on to pre-existing antihypertensive treatment for 6 weeks | Drug | Placebo |
Primary outcome
Albumin/Creatinine Ratio (UACR) in 24h urine change between Baseline and Visit 4
Time frame: up to 14 weeks of study drug intake
12 secondary outcomes
24 hour urinary sodium excretion change between Baseline and Visit 4
Time frame: after 14 weeks of study drug intake
Fasting cystatin C change between Baseline and V4
Time frame: up to 14 weeks of study drug intake
Fasting cGMP change between Baseline and Visit 4
Time frame: after 14 weeks of study drug intake
Fasting serum ADMA change between Baseline and V4
Time frame: up to 14 weeks of study drug intake
Fasting hsCRP change between Baseline and Visit 4
Time frame: up to 14 weeks of study drug intake
Fasting TGF-ß1 change between Baseline and Visit 4
Time frame: after 14 weeks of study drug intake
Retinal endothelial function change between Baseline and Visit 4
Time frame: up to 14 weeks of study drug intake
Retinal microvascular blood flow change between Baseline and Visit 4
Time frame: up to 14 weeks of study drug intake
24h blood pressure measurements change between Baseline and Visit 4
Time frame: up to 14 weeks of study drug intake
HbA1c change between Baseline and Visit 4
Time frame: up to 14 weeks of study drug intake
Body weight change during study participation
Time frame: up to 14 weeks of study drug intake
Adverse events during study participation
Time frame: up to 14 weeks of study drug intake
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Mar 2015.
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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.
Thomas Forst, MD, PhD principal investigator
Profil GmbH Mainz
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 Linagliptin in people with Arterial Hypertension and Albuminuria, run by ikfe-CRO GmbH 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 6 inclusion and 24 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 3 Mar 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 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?
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?
Albumin/Creatinine Ratio (UACR) in 24h urine change between Baseline and Visit 4 (time frame: up to 14 weeks of study drug intake). 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 3 Mar 2015.