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

Charité University Medicine Berlin

Status and phase

Completed

Phase 4

Conditions

Coronary Artery Disease

Hypertension

Type 2 Diabetes Mellitus

Treatments

Other: Placebo

Drug: Valsartan

Study type

Interventional

Funder types

Other

Identifiers

NCT00982358

CVAL489A2423

Ek#2140

Details and patient eligibility

About

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:

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.
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:

To explore the effect of 160/320 mg valsartan on parameters of insulin sensitivity.
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)].
To explore the effect of 160/320 mg valsartan on inflammatory gene expression from monocytes and fat tissue.
To explore the effect of 160/320 mg valsartan on metabolic gene expression in fat tissue.
To explore the effect of 160/320 mg valsartan on coronary perfusion, in the group of patients with angiographically documented CAD.

Sex

All

Ages

30 to 80 years old

Volunteers

No Healthy Volunteers

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