11ß-HSD1 and Metabolic Syndrome

Sponsor

Charite University, Berlin, Germany (Other)

Overall Status

Completed

CT.gov ID

NCT00370305

Collaborator

(none)

Enrollment

Location

Arm

Duration (Months)

0.5

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Metabolic Syndrome Impaired Glucose Tolerance	Drug: rosiglitazone	Phase 2

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 Design

Study Type:

Interventional

Actual Enrollment :

24 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

The Pathogenic Role of 11ß-hydroxysteroid Dehydrogenase in the Metabolic Syndrome - the Effect of Rosiglitazone

Study Start Date :

May 1, 2004

Actual Primary Completion Date :

Oct 1, 2008

Actual Study Completion Date :

Oct 1, 2008

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Rosiglitazone treatment Rosiglitazone will be given to the subjects. All subjects will be analyzed before and after treatment	Drug: rosiglitazone 89 mg BID for 8 weeks, orally Other Names: Avandia

Arm

Intervention/Treatment

Experimental: Rosiglitazone treatment

Rosiglitazone will be given to the subjects. All subjects will be analyzed before and after treatment

Drug: rosiglitazone

89 mg BID for 8 weeks, orally

Other Names:

Avandia

Outcome Measures

Primary Outcome Measures

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

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