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

Hypertension Clinical Trial

Official title:

A 16-weeks, Randomized, Double-blind, Placebo-controlled Study to Evaluate the Anti-inflammatory Actions of 320 mg Diovan in Patients With Type 2 Diabetes With and Without Coronary Artery Disease

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00982358
• Other study ID #: CVAL489A2423
• Secondary ID: Ek#2140
• Status: Completed
• Phase: Phase 4
• First received: September 22, 2009
• Last updated: September 22, 2009
• Start date: July 2004
• Est. completion date: March 2007

Study information

• Verified date: September 2009
• Source: Charite University, Berlin, Germany
• Contact: n/a
• Is FDA regulated: No
• Health authority: Germany: Federal Institute for Drugs and Medical Devices
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 121
• Est. completion date: March 2007
• Est. primary completion date: October 2006
• Gender: Both
• Age group: 30 Years to 80 Years

Eligibility

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

Study Design

Allocation: Randomized, Intervention Model: Parallel Assignment, Masking: Double-Blind, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Coronary Artery Disease
• Coronary Disease
• Diabetes Mellitus
• Diabetes Mellitus, Type 2
• Hypertension
• Myocardial Ischemia
• Type 2 Diabetes Mellitus

Intervention

Drug:
• Valsartan

Other:
• Placebo

Locations

Country	Name	City	State
Germany	Charité University Medicine Berlin, Center for Cardiovascular Research, Outpatient Clinic	Berlin
Germany	University of Ulm, Department of Internal Medicine II	Ulm	Baden-Wuerttemberg

Sponsors (2)

Lead Sponsor	Collaborator
Charite University, Berlin, Germany	University of Ulm

Country where clinical trial is conducted

Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The primary objective of the study was to evaluate the anti-inflammatory effect of VAL by analyzing the reduction of the inflammatory markers interleukin-6 (IL-6) and tumor necrosis factor alpha (TNFa) in serum after 16 weeks of treatment.
Secondary	To explore the effect of 160/320 mg valsartan on parameters of insulin sensitivity.
Secondary	To explore the effect of 160/320 mg valsartan on additional inflammatory markers in plasma
Secondary	To explore the effect of 160/320 mg valsartan on inflammatory gene expression from monocytes and fat tissue
Secondary	To explore the effect of 160/320 mg valsartan on metabolic gene expression in fat tissue.
Secondary	To explore the effect of 160/320 mg valsartan on coronary perfusion, in the group of patients with angiographically documented CAD