In vivo induction of heme oxygenase-1 (HO-1) in the metabolic syndrome (MetS). Influence of heme arginate (Normosang) infusion on heme oxygenase-1 activity, endothelial dysfunction, insulin resistance and adipose tissue inflammation related to the metabolic syndrome

Phase 2

Completed

Conditions: atherosclerosis in the metabolic syndrome
10018424
10003216

Registration Number: NL-OMON34409

Lead Sponsor: niversitair Medisch Centrum Sint Radboud

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Completed

Sex: Not specified

Target Recruitment: 16

Inclusion Criteria

At least 18 and not older than 70 years of age on the day of the first dosing.
Subject is able and willing to sign the Informed Consent Form prior to screening evaluations.
Metabolic syndrome defined by at least three out of five criteria:
Elevated waist circumference (women >= 88, men >= 102 cm).
Elevated triglycerides or drug treatment (>= 1.7 mmol/L).
Reduced HDL-cholesterol or drug treatment (women < 1.3 mmol/L, men < 1.0 mmol/L).
Elevated blood pressure (systolic >= 130 mm Hg and/or diastolic >= 85 mm Hg)
Elevated fasting glucose (>= 6.1 mmol/L)

Exclusion Criteria

History of smoking within the past year.
History of or current abuse of drugs, alcohol or solvents.
Known diabetes mellitus
Repeated systolic blood pressure >= 180 mm Hg in all subjects, >= 160 mm Hg in women >= 65 yrs old and >= 140 mm Hg in men >= 65 yrs old
Fasting plasma glucose > 7.0 mmol/L or HbA1c > 6.2%
Pregnancy or breast feeding (contraception for at least 3 months before inclusion is required for fertile women)
Current use of antihypertensive, cardiac or other vasoactive medication
Current use of acetylsalicylic acid and/or statin
Use of antioxidant vitamin supplements
Clinical evidence of cardiac or pulmonary disease
Laboratory evidence of renal or hepatic abnormalities, defined as results exceeding twice the upper limit of normal range.
Unconjugated hyperbilirubinemia (total bilirubin level > 10 µmol/L and a normal direct bilirubin level) suggesting the Gilbert Syndrome.

Study & Design

Study Type: Interventional

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>Insulin sensitivity assessed by an euglycemic hyperinsulinemic clamp expressed<br /><br>as M-value. Vasodilation / forearm blood flow in response to acetylcholine,<br /><br>assessed by venous occlusion strain gauge plethysmography.</p><br>

Secondary Outcome Measures

Name	Time	Method
<p>Vasodilation / forearm blood flow in response to nitroprusside, assessed by<br /><br>venous occlusion strain gauge plethysmography.Plasma biomarkers of oxidative<br /><br>stress and vascular inflammation and markers of HO expression and activity. </p><br>