11ß-HSD1 and Metabolic Syndrome

Phase 2

Completed

• Conditions: Impaired Glucose Tolerance; Metabolic Syndrome
• Interventions: Drug: rosiglitazone

• Registration Number: NCT00370305
• Lead Sponsor: Charite University, Berlin, Germany

Brief Summary

The purpose of this study is to determine whether the insulin sensitizing effects of rosiglitazone were accompanied by changes in 11ß-HSD1 expression and activity in different tissues. Furthermore the metabolic and hormonal effects of PPAR gamma stimulation by rosiglitazone will be analysed in several tissues.

Detailed Description

The PPARgamma agonist rosiglitazone (R) increases insulin sensitivity, which is comparable to the effects of a reduction in 11ß-hydroxysteroid dehydrogenase type 1 (11β-HSD1) activity in animal models. We therefore aimed to investigate whether rosiglitazone-induced insulin sensitivity is associated with changes in 11β-HSD1 activity in different tissues in subjects suffering from impaired glucose tolerance. Furthermore the metabolic and hormonal effects of PPAR gamma stimulation by rosiglitazone will be analysed in those tissue samples.

Study Timeline

• Study Start: 2004-05
• Study First Submitted: 2006-08-30
• Study First Submitted QC: 2006-08-30
• Study First Posted: 2006-08-31
• Primary Completion: 2008-10
• Study Completion: 2008-10
• Status Verified: 2018-01
• Last Update Submitted: 2018-01-11
• Last Update Posted: 2018-01-16

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 24

Inclusion Criteria

• Impaired glucose tolerance

Exclusion Criteria

• Treatment with insulin
• Orally taken antidiabetic medication, glucocorticoids or vitamin K-antagonists
• Heart failure
• Impaired hepatic or renal function
• Anaemia
• Disturbed coagulation
• Any other endocrine disorder

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Rosiglitazone treatment	rosiglitazone	Rosiglitazone will be given to the subjects. All subjects will be analyzed before and after treatment

Primary Outcome Measures

Name	Time	Method
changes of 11ß-HSD1 expression in adipose tissue and skeletal muscle during 8 weeks of rosiglitazone treatment	8 weeks	11ß-HSD1 expression will be measured in adipose tissue and skeletal muscle
changes of hepatic 11ß-HSD1 activity during 8 weeks of rosiglitazone treatment	8 weeks	11ß-HSD1 activity will be assessed by measuring conversion of cortisone to cortisol (ratio will be calculated)
changes of whole body 11ß-HSD1 activity during 8 weeks of rosiglitazone treatment	8 weeks	whole body 11ß-HSD1 activity will be assessed by measuring the ratio of urinary tetrahydrocortisol (THF) + alpha-tetrahydrocortisol (THF) / tetrahydrocortisone

Secondary Outcome Measures

Name	Time	Method
changes in insulin sensitivity during 8 weeks of rosiglitazone treatment	8 weeks	Measurement of whole body and myocellular insulin sensitivity (mg•kg-1•min-1/(mU•L-1)) before and after treatment
Hormonal and metabolic changes induced by the intervention	3 months	Whole body as well as tissue specific (skeletal muscle and different adipose tissue compartment) changes in hormonal circuits and metabolism will be analyzed
changes of FGF-21 induced by the intervention	8 weeks	FGF-21 (ng/ml) will be assessed in plasma samples
changes of free fatty acids (FFA) induced by the intervention	8 weeks	FFA (mmol/l) will be assessed in plasma samples
changes of myocellular SCD1 expression induced by the intervention	8 weeks	myocellular SCD1 mRNA expression will be assessed
changes of myocellular long chain fatty acids (LC-FA) expression induced by the intervention	8 weeks	myocellular LC-FA mRNA expression will be assessed

Trial Locations

Locations (1)

Charite, Campus Benjamin Franklin; 🇩🇪 Berlin, Germany