Back to resultsRamipril and Clopidogrel in Oxidative Stress, Vascular Inflammation and Endothelial Dysfunction in Type 2 Diabetes and Diabetic Nephropathy
Primary Purpose
Diabetes Type 2, Diabetic Nephropathy, Vascular Disease
Status
Unknown status
Phase
Phase 4
Locations
Greece
Study Type
Interventional
Intervention
Ramipril
Clopidogrel
Sponsored by
About this trial
This is an interventional treatment trial for Diabetes Type 2 focused on measuring 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
Eligibility 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
Sites / Locations
- AHEPA University HospitalRecruiting
- Aristotle University of Thessaloniki/ AHEPA University HospitalRecruiting
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
Active Comparator
Arm Label
ramipril
clopidogrel and ramipril
Arm Description
Ramipril 10 mg tablets. Each dose will be taken orally with water once daily.
clopidogrel 75mg tablet and ramipril 10mg. Each drug will be taken orally with water once daily
Outcomes
Primary Outcome Measures
Changes in Asymmetric dimethylarginine (ADMA) blood levels after the combined treatment with ramipril and clopidogrel compared with ramipril monotherapy
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
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
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
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
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
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
Change from baseline in carotid intima-media thickness after combined therapy with ramipril and clopidogrel and after ramipril monotherapy
Full Information
NCT ID
NCT01743014
First Posted
November 21, 2012
Last Updated
December 4, 2012
Sponsor
AHEPA University Hospital
Collaborators
Aristotle University Of Thessaloniki
1. Study Identification
Unique Protocol Identification Number
NCT01743014
Brief Title
Ramipril and Clopidogrel in Oxidative Stress, Vascular Inflammation and Endothelial Dysfunction in Type 2 Diabetes and Diabetic Nephropathy
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 Type
Interventional
2. Study Status
Record Verification Date
November 2012
Overall Recruitment Status
Unknown status
Study Start Date
July 2012 (undefined)
Primary Completion Date
July 2014 (Anticipated)
Study Completion Date
July 2015 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
AHEPA University Hospital
Collaborators
Aristotle University Of Thessaloniki
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
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.
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Diabetes Type 2, Diabetic Nephropathy, Vascular Disease
Keywords
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
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Crossover Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
60 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
ramipril
Arm Type
Active Comparator
Arm Description
Ramipril 10 mg tablets. Each dose will be taken orally with water once daily.
Arm Title
clopidogrel and ramipril
Arm Type
Active Comparator
Arm Description
clopidogrel 75mg tablet and ramipril 10mg. Each drug will be taken orally with water once daily
Intervention Type
Drug
Intervention Name(s)
Ramipril
Other Intervention Name(s)
Triatec
Intervention Description
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
Intervention Type
Drug
Intervention Name(s)
Clopidogrel
Other Intervention Name(s)
Plavix, Iscover
Intervention Description
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.
Primary Outcome Measure Information:
Title
Changes in Asymmetric dimethylarginine (ADMA) blood levels after the combined treatment with ramipril and clopidogrel compared with ramipril monotherapy
Description
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.
Time Frame
Baseline to week 12 and week 14 to week 26
Title
Changes in High-sensitivity C-reactive protein (HsCRP) blood levels after the combined treatment with ramipril and clopidogrel compared with ramipril monotherapy
Description
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
Time Frame
Baseline to week 12 and week 14 to week 26
Title
Changes in soluble CD40 Ligand (sCD40L)blood levels after the combined treatment with ramipril and clopidogrel compared with ramipril monotherapy
Description
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.
Time Frame
Baseline to week 12 and week 14 to week 26
Title
Changes in urine 8-isoprostane-F2 levels after the combined treatment with ramipril and clopidogrel compared with ramipril monotherapy
Description
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.
Time Frame
Baseline to week 12 and week 14 to week 26
Title
Reduction in albumine to creatine ratio after the combined treatment with ramipril and clopidogrel compared with ramipril monotherapy
Description
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
Time Frame
Baseline to week 12 and week 14 to week 26
Secondary Outcome Measure Information:
Title
Changes in ADMA blood levels after treatment with ramipril
Description
Evaluation of the effect of ramipril, as antihypertensive therapy, in endothelial dysfunction in patients with diabetes mellitus type 2 and diabetic nephropathy
Time Frame
baseline to week 26
Title
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
Title
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
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
Eligibility 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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Fotios S Iliadis, Lecturer of Internal Medicine
Phone
+306974960728
Email
iliadis@med.auth.gr
First Name & Middle Initial & Last Name or Official Title & Degree
Vaia F Bougatsa, Resident of internal medicine
Phone
+306944334265
Email
vaiaboug@yahoo.gr
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Fotios S Iliadis, Lecturer of Internal Medicine
Organizational Affiliation
AHEPA University Hospital/ Aristotle University of Thessaloniki
Official's Role
Study Director
First Name & Middle Initial & Last Name & Degree
Vaia F Bougatsa, Resident of Internal Medicine
Organizational Affiliation
AHEPA University Hospital/ Aristotle University of Thessaloniki
Official's Role
Principal Investigator
Facility Information:
Facility Name
AHEPA University Hospital
City
Thessaloniki
ZIP/Postal Code
546 36
Country
Greece
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Fotios S Iliadis, Lecturer of Internal Medicine
Phone
+302310993587
Email
iliadis@med.auth.gr
First Name & Middle Initial & Last Name & Degree
Vaia F Bougatsa, Resident of Internal Medicine
Phone
+306944334265
Email
vaiabou@yahoo.gr
Facility Name
Aristotle University of Thessaloniki/ AHEPA University Hospital
City
Thessaloniki
Country
Greece
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Vaia F Bougatsa, MD
12. IPD Sharing Statement
Citations:
PubMed Identifier
35224730
Citation
Natale P, Palmer SC, Saglimbene VM, Ruospo M, Razavian M, Craig JC, Jardine MJ, Webster AC, Strippoli GF. Antiplatelet agents for chronic kidney disease. Cochrane Database Syst Rev. 2022 Feb 28;2(2):CD008834. doi: 10.1002/14651858.CD008834.pub4.
Results Reference
derived
Learn more about this trial
Ramipril and Clopidogrel in Oxidative Stress, Vascular Inflammation and Endothelial Dysfunction in Type 2 Diabetes and Diabetic Nephropathy
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