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Ramipril and Clopidogrel in Oxidative Stress, Vascular Inflammation and Endothelial Dysfunction in Type 2 Diabetes and Diabetic Nephropathy

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ClinicalTrials.gov Identifier: NCT01743014
Recruitment Status : Unknown
Verified November 2012 by Vaia Bougatsa, AHEPA University Hospital.
Recruitment status was:  Recruiting
First Posted : December 6, 2012
Last Update Posted : December 6, 2012
Sponsor:
Collaborator:
Aristotle University Of Thessaloniki
Information provided by (Responsible Party):
Vaia Bougatsa, AHEPA University Hospital

Study Description
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Brief Summary:
The purpose of this study is to determine whether the combination with ramipril and clopidogrel leads to further improvement of endothelial function, reduction of oxidative stress and reduction of vascular inflammation, compared with ramipril monotherapy, in patients with Diabetes Mellitus type 2 and diabetic nephropathy.

Condition or disease Intervention/treatment Phase
Diabetes Type 2 Diabetic Nephropathy Vascular Disease Drug: Ramipril Drug: Clopidogrel Phase 4

Detailed Description:
  • Cardiovascular disease is the leading cause of deaths in diabetic population with diabetic nephropathy.
  • Pharmacologic therapy for patients with diabetes and hypertension should be with a regimen that includes either an angiotensin-converting-enzyme inhibitor (ACEi) or an angiotensin receptor blocker (ARB)
  • Diabetic patients at increased cardiovascular risk should receive an antiplatelet agent for primary prevention.

Methods:

An open label,randomized, two period cross-over design study, involving patients with type 2 diabetes and diabetic nephropathy. After a 4 weeks wash out period for ACE inhibitors or Angiotensin receptor blockers (week 0, baseline) 60 patients will be randomized to receive ramipril(10 mg) only or ramipril (10 mg) and clopidogrel (75mg) for 12 weeks exchanging their treatment for a further 12 weeks, after a 2 week wash out period for clopidogrel. Patients will be examined and measurements will be taken at baseline (week 0), and at the end of 12, 14, and 26 weeks.

Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 60 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Prospective, Randomized, Two Period, With an Intermediate Wash Out Period, Cross-over Study to Compare the Effects of Either Combined Therapy With Ramipril and Clopidogrel or Ramipril Monotherapy on Oxidative Stress, Vascular Inflammation and Endothelial Dysfunction in Patients With Type 2 Diabetes and Diabetic Nephropathy
Study Start Date : July 2012
Estimated Primary Completion Date : July 2014
Estimated Study Completion Date : July 2015

Resource links provided by the National Library of Medicine


Arms and Interventions
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Arm Intervention/treatment
Active Comparator: ramipril
Ramipril 10 mg tablets. Each dose will be taken orally with water once daily.
 Drug: Ramipril
Patients will receive 10 mg ramipril throughout the study. Each dose will be taken orally once daily. The duration of treatment with ramipril is 26 weeks
Other Name: Triatec
Active Comparator: clopidogrel and ramipril
clopidogrel 75mg tablet and ramipril 10mg. Each drug will be taken orally with water once daily
 Drug: Ramipril
Patients will receive 10 mg ramipril throughout the study. Each dose will be taken orally once daily. The duration of treatment with ramipril is 26 weeks
Other Name: Triatec

Drug: Clopidogrel
12 weeks treatment with ramipril 10 mg and clopidogrel 75 mg once daily followed by a 2 week wash out period for clopidogrel and subsequently additional 12 weeks treatment wit both drugs after cross over.
Other Names:
  • Plavix
  • Iscover


Outcome Measures
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Primary Outcome Measures :
  1. Changes in Asymmetric dimethylarginine (ADMA) blood levels after the combined treatment with ramipril and clopidogrel compared with ramipril monotherapy [ Time Frame: Baseline to week 12 and week 14 to week 26 ]
    The primary aim is to investigate the effect of the combined treatment with ramipril and clopidogrel versus ramipril monotherapy in ADMA as biomarker of endothelial dysfunction.

  2. Changes in High-sensitivity C-reactive protein (HsCRP) blood levels after the combined treatment with ramipril and clopidogrel compared with ramipril monotherapy [ Time Frame: Baseline to week 12 and week 14 to week 26 ]
    The primary aim is to investigate the effect of the combined treatment with ramipril and clopidogrel versus ramipril monotherapy in hsCRP as biomarker of vascular inflammation

  3. Changes in soluble CD40 Ligand (sCD40L)blood levels after the combined treatment with ramipril and clopidogrel compared with ramipril monotherapy [ Time Frame: Baseline to week 12 and week 14 to week 26 ]
    The primary aim is to investigate the effect of the combined treatment with ramipril and clopidogrel versus ramipril monotherapy in soluble CD40 Ligand as biomarker of vascular inflammation.

  4. Changes in urine 8-isoprostane-F2 levels after the combined treatment with ramipril and clopidogrel compared with ramipril monotherapy [ Time Frame: Baseline to week 12 and week 14 to week 26 ]
    The primary aim is to investigate the effect of the combined treatment with ramipril and clopidogrel versus ramipril monotherapy in urine 8-isoprostane-F2 as biomarker of oxidative stress.

  5. Reduction in albumine to creatine ratio after the combined treatment with ramipril and clopidogrel compared with ramipril monotherapy [ Time Frame: Baseline to week 12 and week 14 to week 26 ]
    The primary aim is to investigate the effect of the combined treatment with ramipril and clopidogrel versus ramipril monotherapy in albumine to creatine ratio as an index of cardiovascular disease


Secondary Outcome Measures :
  1. Changes in ADMA blood levels after treatment with ramipril [ Time Frame: baseline to week 26 ]
    Evaluation of the effect of ramipril, as antihypertensive therapy, in endothelial dysfunction in patients with diabetes mellitus type 2 and diabetic nephropathy

  2. Increase of Glomerular Filtration Rate (GFR) after combined treatment with ramipril and clopidogrel and after ramipril monotherapy [ Time Frame: baseline to week 12 and week 14 to week 26 ]
  3. Change from baseline in carotid intima-media thickness after combined therapy with ramipril and clopidogrel and after ramipril monotherapy [ Time Frame: baselibe to week 12 and week 14 to week 26 ]

Eligibility Criteria
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Ages Eligible for Study:   18 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria: type 2 diabetes patients with diabetic nephropathy in the range of micro- or macroalbuminuria and

  • HbA1c(glycosylated haemoglobin A1c <7%
  • Blood pressure ≤130/80 mmHg
  • LDL (Low Density Lipoproteins) <100 mg/dl
  • Informed consent

Exclusion Criteria:

  • patients with diabetic nephropathy and estimated GFR <30ml/min with Modification of Diet in Renal Disease equation (MDRD equation)
  • baseline potassium > 5.2 meq/L
  • patients with nephrotic proteinuria defined as albumine to creatinine ratio (ACR)> 3.5 g/g or as proteinuria >3.5 g per 1.73 m2 per 24 hours
  • history or evidence of non-diabetic kidney disease
  • history of stroke, peripheral artery disease, coronary artery disease
  • history or evidence of a secondary form of hypertension
  • history of severe hepatic failure, malignancy, severe endocrinopathy,autoimmune disease or chronic inflammatory disease
  • any known bleeding or platelet disorder or platelets <100.000/μL
  • heart failure in New York Heart Association(NYHA) functional class II-IV
  • inability or unwillingness on the part of the patient to sign the Patient Consent Form
  • known hypersensitivity to ramipril or to clopidogrel
  • Women of child-bearing potential
  • use of oral anticoagulants or other antithrombotic treatment
  • use of glitazones
  • patients receiving statins should be on a stable dose of at least 3 months prior to study initiation and dose should be constant during the study
  • any surgical or medical condition which in the opinion of the investigator may expose the patient to a higher risk in participation in the study
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01743014


Contacts
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Contact: Fotios S Iliadis, Lecturer of Internal Medicine +306974960728 iliadis@med.auth.gr
Contact: Vaia F Bougatsa, Resident of internal medicine +306944334265 vaiaboug@yahoo.gr

Locations
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Greece
AHEPA University Hospital Recruiting
Thessaloniki, Greece, 546 36
Contact: Fotios S Iliadis, Lecturer of Internal Medicine    +302310993587    iliadis@med.auth.gr   
Contact: Vaia F Bougatsa, Resident of Internal Medicine    +306944334265    vaiabou@yahoo.gr   
Aristotle University of Thessaloniki/ AHEPA University Hospital Recruiting
Thessaloniki, Greece
Principal Investigator: Vaia F Bougatsa, MD         
Sponsors and Collaborators
AHEPA University Hospital
Aristotle University Of Thessaloniki
Investigators
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Study Director: Fotios S Iliadis, Lecturer of Internal Medicine AHEPA University Hospital/ Aristotle University of Thessaloniki
Principal Investigator: Vaia F Bougatsa, Resident of Internal Medicine AHEPA University Hospital/ Aristotle University of Thessaloniki
More Information
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Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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Responsible Party: Vaia Bougatsa, Medical Doctor-Resident of Internal Medicine, AHEPA University Hospital
ClinicalTrials.gov Identifier: NCT01743014    
Other Study ID Numbers: 15/10-7-2012
First Posted: December 6, 2012    Key Record Dates
Last Update Posted: December 6, 2012
Last Verified: November 2012
Keywords provided by Vaia Bougatsa, AHEPA University Hospital:
diabetes
diabetic nephropathy
vascular inflammation
oxidative stress
endothelial dysfunction
Asymmetric dimethylarginine
 High sensitivity CRP
albumine to creatinine ratio
isoprostane
clopidogrel
ramipril
carotid intima media thickness
Additional relevant MeSH terms:
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Kidney Diseases
Diabetic Nephropathies
Vascular Diseases
Diabetes Mellitus
Diabetes Mellitus, Type 2
Inflammation
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Pathologic Processes
Urologic Diseases
Cardiovascular Diseases
Diabetes Complications
Ramipril
 Clopidogrel
Platelet Aggregation Inhibitors
Purinergic P2Y Receptor Antagonists
Purinergic P2 Receptor Antagonists
Purinergic Antagonists
Purinergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs
Angiotensin-Converting Enzyme Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Antihypertensive Agents