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

Purpose

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	Intervention	Phase
Diabetes Type 2 Diabetic Nephropathy Vascular Disease	Drug: Ramipril Drug: Clopidogrel	Phase 4

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Efficacy Study Intervention Model: Crossover Assignment Masking: 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

Resource links provided by NLM:

MedlinePlus related topics: Diabetes Diabetes Type 2 Diabetic Kidney Problems Vascular Diseases

Drug Information available for: Ramipril Clopidogrel bisulfate

U.S. FDA Resources

Further study details as provided by AHEPA University Hospital:

Primary Outcome Measures:

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 ] [ Designated as safety issue: No ]
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.
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 ] [ Designated as safety issue: No ]
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
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 ] [ Designated as safety issue: No ]
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.
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 ] [ Designated as safety issue: No ]
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.
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 ] [ Designated as safety issue: No ]
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:

Changes in ADMA blood levels after treatment with ramipril [ Time Frame: baseline to week 26 ] [ Designated as safety issue: No ]
Evaluation of the effect of ramipril, as antihypertensive therapy, in endothelial dysfunction in patients with diabetes mellitus type 2 and diabetic nephropathy
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 ] [ Designated as safety issue: No ]
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 ] [ Designated as safety issue: No ]

Estimated Enrollment:	60
Study Start Date:	July 2012
Estimated Study Completion Date:	July 2015
Estimated Primary Completion Date:	July 2014 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
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

Arms

Assigned Interventions

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

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.

Eligibility

Ages Eligible for Study:	18 Years to 80 Years
Genders Eligible for Study:	Both
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

Please refer to this study by its ClinicalTrials.gov identifier: NCT01743014

Contacts

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

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

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

No publications provided

Responsible Party:	Vaia Bougatsa, Medical Doctor-Resident of Internal Medicine, AHEPA University Hospital
ClinicalTrials.gov Identifier:	NCT01743014 History of Changes
Other Study ID Numbers:	15/10-7-2012
Study First Received:	November 21, 2012
Last Updated:	December 4, 2012
Health Authority:	Greece: Aristotle University of Thessaloniki

Keywords provided by 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:

Diabetes Mellitus
Diabetes Mellitus, Type 2
Diabetic Nephropathies
Inflammation
Kidney Diseases
Vascular Diseases
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Urologic Diseases
Diabetes Complications
Pathologic Processes
Cardiovascular Diseases
N,N-dimethylarginine
Ramipril

Clopidogrel
Ticlopidine
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Platelet Aggregation Inhibitors
Hematologic Agents
Therapeutic Uses
Purinergic P2Y Receptor Antagonists
Purinergic P2 Receptor Antagonists
Purinergic Antagonists
Purinergic Agents
Neurotransmitter Agents
Physiological Effects of Drugs
Fibrinolytic Agents

ClinicalTrials.gov processed this record on May 16, 2013