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

NCT00982358 | Completed Phase 4

• 2 other identifiers: CVAL489A2423Ek#2140
• Study Type: interventional
• Target: 121
• Locations: 1 country
• Sites: 2

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. 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. 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.
3. 3.To explore the effect of 160/320 mg valsartan on parameters of insulin sensitivity.
4. 4.To explore the effect of 160/320 mg valsartan on additional inflammatory markers in plasma \[e.g. C-Reactive protein (CRP), soluble intracellular adhesion molecule-1 (sICAM-1), soluble vascular cell adhesion molecule-1 (sVCAM-1), serum amyloid A (SAA), soluble CD40 ligand (sCD40L), fibrinogen, Interleukin 1β (IL-1β), matrix metalloproteases -2, -3 and -9 (MMP-2, -3, -9), and sE-selectin)\].
5. 5.To explore the effect of 160/320 mg valsartan on inflammatory gene expression from monocytes and fat tissue.
6. 6.To explore the effect of 160/320 mg valsartan on metabolic gene expression in fat tissue.
7. 7.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

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (5)

• 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

Study Arms (2)

Placebo

PLACEBO COMPARATOR

Other: Placebo

Valsartan

ACTIVE COMPARATOR

Drug: Valsartan

Interventions

Valsartan DRUG

Valsartan

Placebo OTHER

Placebo

Eligibility Criteria

• Age: 30 Years - 80 Years
• Sex: all
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Charite University, Berlin, Germany: lead
• University of Ulm: collaborator

Study Sites (2)

University of Ulm, Department of Internal Medicine II

Ulm, Baden-Wurttemberg, 89081, Germany

Location

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

Berlin, State of Berlin, 10115, Germany

Location

MeSH Terms

Conditions

Hypertension; Diabetes Mellitus, Type 2; Coronary Artery Disease

Interventions

Valsartan

Condition Hierarchy (Ancestors)

Vascular Diseases; Cardiovascular Diseases; Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Coronary Disease; Myocardial Ischemia; Heart Diseases; Arteriosclerosis; Arterial Occlusive Diseases

Intervention Hierarchy (Ancestors)

Tetrazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Valine; Amino Acids, Branched-Chain; Amino Acids; Amino Acids, Peptides, and Proteins; Amino Acids, Essential

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: September 22, 2009
• First Posted: September 23, 2009
• Study Start: July 1, 2004
• Primary Completion: October 1, 2006
• Study Completion: March 1, 2007
• Last Updated: September 23, 2009

Record last verified: 2009-09

Locations

DE (2)