Anti-Inflammatory Actions of Valsartan in Patients With Type 2 Diabetes Mellitus

NCT ID: NCT00982358

Last Updated: 2009-09-23

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 121 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2004-07-31
• Study Completion Date: 2007-03-31

Brief Summary

This study is designed to support the use of valsartan in the diabetic population. Two different groups will be studied, one with and one without coronary artery disease (CAD) documented by angiography.

The study is intended to demonstrate that valsartan 320 mg has an anti-inflammatory potential, reducing inflammatory serum markers as well as inflammatory gene expression, and to show that valsartan is able to improve metabolic parameters in this patient population. Furthermore, in the subgroup of patients with documented CAD this study wants to show that valsartan improves coronary perfusion.

3 Objectives

Primary objectives:

1. To demonstrate the anti-inflammatory efficacy of valsartan 160/320 mg by testing the hypothesis of superiority compared to placebo in the reduction of the inflammatory marker Tumor necrosis factor alpha (TNFα) in plasma after 16 weeks of treatment in hypertensive patients with type 2 diabetes mellitus.

2. To demonstrate the anti-inflammatory efficacy of valsartan 160/320 mg by testing the hypothesis of superiority compared to placebo in the reduction of the inflammatory marker Interleukin 6 (IL-6) in plasma after 16 weeks of treatment in hypertensive patients with type 2 diabetes mellitus.

Secondary objectives:

1. To explore the effect of 160/320 mg valsartan on parameters of insulin sensitivity.

2. To explore the effect of 160/320 mg valsartan on additional inflammatory markers in plasma [e.g. C-Reactive protein (CRP), soluble intracellular adhesion molecule-1 (sICAM-1), soluble vascular cell adhesion molecule-1 (sVCAM-1), serum amyloid A (SAA), soluble CD40 ligand (sCD40L), fibrinogen, Interleukin 1β (IL-1β), matrix metalloproteases -2, -3 and -9 (MMP-2, -3, -9), and sE-selectin)].

3. To explore the effect of 160/320 mg valsartan on inflammatory gene expression from monocytes and fat tissue.

4. To explore the effect of 160/320 mg valsartan on metabolic gene expression in fat tissue.

5. To explore the effect of 160/320 mg valsartan on coronary perfusion, in the group of patients with angiographically documented CAD.

Conditions

Hypertension; Type 2 Diabetes Mellitus; Coronary Artery Disease

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Placebo

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: OTHER

Valsartan

Group Type: ACTIVE_COMPARATOR

Valsartan

Intervention Type: DRUG

Interventions

Valsartan

Intervention Type: DRUG

Placebo

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

• Male or female patients between 30 and 80 years old, inclusive
• Controlled type 2 Diabetes Mellitus on stable treatment at least during the 4 weeks prior to visit 1
• Treated or untreated stage 1 (according to JNC VII Guidelines) or grade 1 (according to ESH/ESC 2003 Guidelines) hypertensive patients
• For one stratum: angiographically proven CAD
• Signed informed consent prior to any study procedure

Exclusion Criteria

• Hypertension classified as stage 2 (or grade 2) or higher
• Normotensive patients, i.e. patients who do not have a history of high blood pressure, and who are not receiving any antihypertensive medication
• Treatment with more than 2 antihypertensive medications
• Current treatment with ARBs
• Glycated hemoglobin (HbA1c) >8.5% at Visit 1
• Current treatment with glitazones
• Myocardial infarction less than 3 months prior to Visit 1
• Total cholesterol >7.8 mmol/l
• Past diagnosis of any systemic inflammatory disease
• Known or suspected contraindications, including history of allergy to angiotensin receptor blockers
• History of hypertensive encephalopathy or cerebrovascular accident less than 1 year prior to Visit 1
• Known Keith-Wagener grade III or IV hypertensive retinopathy
• History of heart failure
• Second or third degree heart block without a pacemaker
• Concomitant unstable angina pectoris
• Concurrent potential life threatening arrhythmia or symptomatic arrhythmia
• Clinically significant valvular heart disease
• Evidence of hepatic disease as determined by any one of the following: ALT or AST values > 2 x ULN at Visit 1, a history hepatic encephalopathy, a history of esophageal varices, or a history of portocaval shunt
• Evidence of renal impairment as determined by any one of the following: serum creatinine >1.25 x ULN at visit 1, a history of dialysis, or a history of nephritic syndrome
• Sodium value <132 mmol/L at Visit 1
• Serum potassium values <3.5 mmol/L or >5.5 mmol/L at visit 1
• Any surgical or medical condition which might alter the absorption, distribution, metabolism, excretion of any drug
• Female patients who are not either post-menopausal for one year of surgically sterile, and who are not using effective contraceptive methods such as barrier method with spermicidal or an intra-uterine device. Oral contraceptive use or dermal implants as the only means of contraception are disallowed
• Pregnant or lactating females
• Any surgical or medical condition which, at the discretion of the investigator, place the patient at higher risk from his/her participation in the study, or are likely to prevent the patients from complying with the requirements of the study or completing the trial period
• History of malignancy including leukemia and lymphoma within 5 years prior to Visit 1
• History of any severe, life threatening disease within the past five years
• Any previous history of a systemic autoimmune disease
• History of drug or alcohol abuse within the last two years
• Participation in any investigational drug trial within one month prior to visit 1

• Minimum Eligible Age: 30 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Ulm

OTHER

Sponsor Role: collaborator

Charite University, Berlin, Germany

OTHER

Sponsor Role: lead

Responsible Party

Charité-University Medicine Berlin, Germany

Locations

University of Ulm, Department of Internal Medicine II

Ulm, Baden-Wurttemberg, Germany

Charité University Medicine Berlin, Center for Cardiovascular Research, Outpatient Clinic

Berlin, State of Berlin, Germany

Countries

Germany

Other Identifiers

Ek#2140

Identifier Type: -

Identifier Source: secondary_id

CVAL489A2423

Identifier Type: -

Identifier Source: org_study_id