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 - In vivo induction of HO in MetS.

Phase 1

• Conditions: Subjects suffer from the metabolic syndrome. Effects of study medication on insulin resistance and vascular function will be studied respectively.; MedDRA version: 12.1Level: LLTClassification code 10022489Term: Insulin resistance; MedDRA version: 12.1Level: LLTClassification code 10052066Term: Metabolic syndrome; MedDRA version: 12.1Level: LLTClassification code 10048554Term: Endothelial dysfunction

• Registration Number: EUCTR2010-020875-22-NL
• Lead Sponsor: RUNMC

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2010-06-24
• Last Update Posted: 21 December 2021

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• 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)

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

Documented history of sensitivity/idiosyncrasy to medicinal products or excipients.
History of smoking within the past year.
History of or current abuse of drugs, alcohol or solvents.
Known diabetes mellitus
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
Use of antioxidant vitamin supplements
Inability to suspend the use of statins during trial participation
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.
Inability to understand the nature and extent of the trial and the procedures required.
Participation in a drug trial within 60 days prior to the first dose.
Febrile illness within 3 days before the first dose.
Unconjugated hyperbilirubinemia (total bilirubin level > 10 µmol/L and a normal direct bilirubin level) suggesting the Gilbert Syndrome.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: Our main objective is to determine the effect of HO-1 induction by heme arginate infusion on insulin resistance related to MetS. ;Secondary Objective: Secondary objectives are to determine the effect on endothelial dysfunction, adipose tissue, markers for oxidative stress and vascular inflammation and indicators of HO activity.;Primary end point(s): Insulin sensitivity derived from the glucose infusion rate measured by euglycemic hyperinsulinemic clamps following treatment with Normosang and arginine.