Effects of Saxagliptin on Endothelial Function (ESENDI)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Roland E. Schmieder, University of Erlangen-Nürnberg Medical School
ClinicalTrials.gov Identifier:
NCT01319357
First received: March 17, 2011
Last updated: February 11, 2014
Last verified: February 2014
  Purpose

Diabetes mellitus is a metabolic disease with a growing prevalence worldwide. Currently available therapies for type 2 diabetes have various limitations and are associated with increased risk of hypoglycemia, weight gain, gastrointestinal side effects or edema and heart failure.

A new and promising class of drugs are the gliptins. Several efficacy studies demonstrated a significant improvement of HbA1c with gliptins. In addition, gliptins improved fasting as well as prandial glucose levels and did not induce weight gain. Due to these positive metabolic effects in combination with a very small spectrum of side effects gliptins might very well be part of the standard therapy for type 2 diabetes in the future.

Apart form surrogate parameters like reduction of fasting and postprandial blood glucose levels or improvement of HbA1c, the effect of gliptins on micro- and macrovascular function and cardiovascular outcome has not been the primary focus of current studies. Diabetes mellitus is strongly associated with microangiopathy and macroangiopathy and is a strong independent risk factor for cardiovascular disease and cardiovascular mortality. Endothelial dysfunction which plays a crucial role in the atherosclerotic process is commonly observed in patients with diabetes mellitus and already prediabetes and has - amongst other factors - been linked to fasting and postprandial hyperglycemia. Taken into account that gliptins reduce hyperglycemia and hyperglycemic peaks by preventing inactivation of GLP-1, which exerted beneficial effects on the endothelium in previous studies it is of major interest whether therapy with gliptins improves endothelial function.


Condition Intervention Phase
Diabetes Mellitus Type 2
Drug: Saxagliptin
Drug: Placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: Effects of Saxagliptin on Endothelial Function in Patients With Type 2 Diabetes

Resource links provided by NLM:


Further study details as provided by University of Erlangen-Nürnberg Medical School:

Primary Outcome Measures:
  • effect of saxagliptin compared to placebo on endothelial and vascular function of the retinal circulation [ Time Frame: after 6 weeks of treatment with saxagliptin vs. 6 weeks of treatment with placebo (12 weeks in all) ] [ Designated as safety issue: No ]
    retinal circulation. By applying Scanning-Laser-Doppler-Flowmetry, the change of retinal capillary flow after i.v. L-NMMA application


Enrollment: 52
Study Start Date: October 2010
Study Completion Date: April 2013
Primary Completion Date: April 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: Placebo
Placebo
Drug: Placebo
orally for 6 weeks
Other Name: Placebo
Active Comparator: Saxagliptin
saxagliptin 5 mg/day during 6 weeks
Drug: Saxagliptin
orally 5 mg/d for 6 weeks
Other Name: Onglyza

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion criteria:

  • Type 2 diabetes mellitus defined by fasting glucose ≥126 mg/dl or HbA1c ≥6.5% or on blood glucose lowering medication
  • Age of 18 - 75 years
  • Male and Female patients are eligible. Females of child bearing potential or within two years of the menopause are only eligible if pregnancy test at the screening visit is negative and they use adequate contraceptive precautions during the trial.
  • The patient must demonstrate that she/he is able and willing to perform blood glucose measurements as necessary for Home Blood Glucose Monitoring by herself/himself after it was demonstrated to her/him.

Exclusion Criteria:

  • Any other form of diabetes mellitus than type 2 diabetes mellitus
  • Patients with more than on one blood glucose lowering medication or on insulin therapy
  • Last measured HbA1c > 11%
  • Blood pressure levels ≥180/110 mmHg
  • Body mass index >50 kg/m²
  • Triglyceride levels >1000 mg/dl
  • HDL-cholesterol levels <25 mg/dl
  • Estimated creatinine clearance < 50 ml/min/1.73m²
  • Macroalbuminuria defined by urinary albumine-to-creatinine ratio > 300 mg/g
  • Known liver function test >3 times upper limit of normal
  • Pregnant or breast-feeding patients
  • Current or previous (within 6 months) treatment with an incretin-based therapy such as DPP 4 inhibitors and/or GLP-1 mimetics
  • Any patient currently receiving chronic (>30 consecutive days) treatment with an oral corticosteroid
  • Acute cardiovascular event (including myocardial infarction, unstable angina pectoris, percutaneous coronary intervention, heart failure, stroke, TIA. PRIND, intracerebral bleeding) <6 months prior to screening visit (visit 1)
  • Diabetic retinopathy
  • History of epilepsia or history of seizures
  • Patients being treated for severe auto immune disease e.g. lupus
  • Involvement in the planning and/or conduct of the study (applies to both AstraZeneca and BMS or representative staff and/or staff at the study site)
  • Previous randomisation in the present study
  • Participation in another clinical study within 30 days prior to visit 1
  • Individuals at risk for poor protocol or medication compliance
  • Subject who do not give written consent, that pseudonymous data will be transferred in line with the duty of documentation and the duty of notification according to § 12 and § 13 GCP-V
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01319357

Locations
Germany
Clinical Research Center, Department of Nephrology and Hypertension, University of Erlangen-Nuremberg
Erlangen, Germany, 91054
Sponsors and Collaborators
University of Erlangen-Nürnberg Medical School
Investigators
Principal Investigator: Roland E Schmieder, MD University of Erlangen-Nürnberg
  More Information

Publications:
Responsible Party: Roland E. Schmieder, Prof. Dr. med., University of Erlangen-Nürnberg Medical School
ClinicalTrials.gov Identifier: NCT01319357     History of Changes
Other Study ID Numbers: SAXA24011980GLIPTIN
Study First Received: March 17, 2011
Last Updated: February 11, 2014
Health Authority: Germany: Federal Institute for Drugs and Medical Devices

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 2
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Saxagliptin
Incretins
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Pharmacologic Actions
Dipeptidyl-Peptidase IV Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Hypoglycemic Agents

ClinicalTrials.gov processed this record on August 28, 2014