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

September 22, 2009 updated by: Charite University, Berlin, Germany

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

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment

121

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Germany
      • Berlin, Germany, 10115
        • Charité University Medicine Berlin, Center for Cardiovascular Research, Outpatient Clinic
    • Baden-Wuerttemberg
      • Ulm, Baden-Wuerttemberg, Germany, 89081
        • University of Ulm, Department of Internal Medicine II

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

30 years to 80 years (Adult, Older Adult)

Accepts Healthy Volunteers

N/A

Genders Eligible for Study

All

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Placebo Comparator: Placebo
Other: Placebo
Active Comparator: Valsartan
Drug: Valsartan

What is the study measuring?

Primary Outcome Measures

Outcome Measure
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 (TNFα) in serum after 16 weeks of treatment.

Secondary Outcome Measures

Outcome Measure
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
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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Charite University, Berlin, Germany

Collaborators

University of Ulm

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

July 1, 2004

Primary Completion (Actual)

October 1, 2006

Study Completion (Actual)

March 1, 2007

Study Registration Dates

First Submitted

September 22, 2009

First Submitted That Met QC Criteria

September 22, 2009

First Posted (Estimate)

September 23, 2009

Study Record Updates

Last Update Posted (Estimate)

September 23, 2009

Last Update Submitted That Met QC Criteria

September 22, 2009

Last Verified

September 1, 2009

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CVAL489A2423
  • Ek#2140

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Coronary Artery Disease

Clinical Trials on Placebo

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Israel

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

3
Subscribe