Effects of Linagliptin on Endothelial- , Renal-, and Retinal Function in Patients With Hypertension and Albuminuria

NCT02376075 | Completed Phase 3

• 2 other identifiers: ikfe-Lina-0032012-004300-35
• Study Type: interventional
• Target: 43
• Locations: 1 country
• Sites: 1

Brief 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. 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

Outcome Measures

Primary Outcomes (1)

• Albumin/Creatinine Ratio (UACR) in 24h urine change between Baseline and Visit 4

  up to 14 weeks of study drug intake

Secondary Outcomes (12)

• 24 hour urinary sodium excretion change between Baseline and Visit 4

  after 14 weeks of study drug intake

• Fasting cystatin C change between Baseline and V4

  up to 14 weeks of study drug intake

• Fasting cGMP change between Baseline and Visit 4

  after 14 weeks of study drug intake

• Fasting serum ADMA change between Baseline and V4

  up to 14 weeks of study drug intake

• Fasting hsCRP change between Baseline and Visit 4

  up to 14 weeks of study drug intake

Study Arms (2)

Placebo

PLACEBO COMPARATOR

Placebo, tablets, administered once daily as add on to pre-existing antihypertensive treatment

Drug: Placebo

Linagliptin

ACTIVE COMPARATOR

Linagliptin, tablets containing 5 mg, administered once daily as add on to pre-existing antihypertensive treatment

Drug: Linagliptin

Interventions

Linagliptin DRUG

Intake of tablets containing 5 mg Linagliptin, administered once daily as add on to pre-existing antihypertensive treatment for 6 weeks

Also known as: Trajenta

Linagliptin

Placebo DRUG

Intake of Placebo, administered once daily as add on to pre-existing antihypertensive treatment for 6 weeks

Placebo

Eligibility Criteria

• Age: 45 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• ikfe-CRO GmbH: lead
• Ikfe GmbH: collaborator
• MLM Medical Labs GmbH: collaborator

Study Sites (1)

Profil Mainz GmbH & Co. KG

Mainz, Rhineland-Palatinate, 55116, Germany

Location

MeSH Terms

Conditions

Hypertension; Albuminuria

Interventions

Linagliptin

Condition Hierarchy (Ancestors)

Vascular Diseases; Cardiovascular Diseases; Proteinuria; Urination Disorders; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Urological Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Quinazolines

Study Officials

• Thomas Forst, MD, PhD

  Profil GmbH Mainz

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, OUTCOMES ASSESSOR
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 11, 2015
• First Posted: March 3, 2015
• Study Start: January 1, 2013
• Primary Completion: September 1, 2014
• Study Completion: September 1, 2014
• Last Updated: March 3, 2015

Record last verified: 2015-02

Locations

DE (1)