11ß-HSD1 and Metabolic Syndrome
Primary Purpose
Metabolic Syndrome, Impaired Glucose Tolerance
Status
Completed
Phase
Phase 2
Locations
Germany
Study Type
Interventional
Intervention
rosiglitazone
Sponsored by
About this trial
This is an interventional treatment trial for Metabolic Syndrome focused on measuring 11ß-hydroxysteroid dehydrogenase, rosiglitazone, insulin sensitivity, Impaired glucose tolerance
Eligibility Criteria
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
Sites / Locations
- Charite, Campus Benjamin Franklin
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Rosiglitazone treatment
Arm Description
Rosiglitazone will be given to the subjects. All subjects will be analyzed before and after treatment
Outcomes
Primary Outcome Measures
changes of 11ß-HSD1 expression in adipose tissue and skeletal muscle during 8 weeks of rosiglitazone treatment
11ß-HSD1 expression will be measured in adipose tissue and skeletal muscle
changes of hepatic 11ß-HSD1 activity during 8 weeks of rosiglitazone treatment
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
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
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
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
FGF-21 (ng/ml) will be assessed in plasma samples
changes of free fatty acids (FFA) induced by the intervention
FFA (mmol/l) will be assessed in plasma samples
changes of myocellular SCD1 expression induced by the intervention
myocellular SCD1 mRNA expression will be assessed
changes of myocellular long chain fatty acids (LC-FA) expression induced by the intervention
myocellular LC-FA mRNA expression will be assessed
Full Information
NCT ID
NCT00370305
First Posted
August 30, 2006
Last Updated
January 11, 2018
Sponsor
Charite University, Berlin, Germany
1. Study Identification
Unique Protocol Identification Number
NCT00370305
Brief Title
11ß-HSD1 and Metabolic Syndrome
Official Title
The Pathogenic Role of 11ß-hydroxysteroid Dehydrogenase in the Metabolic Syndrome - the Effect of Rosiglitazone
Study Type
Interventional
2. Study Status
Record Verification Date
January 2018
Overall Recruitment Status
Completed
Study Start Date
May 2004 (undefined)
Primary Completion Date
October 2008 (Actual)
Study Completion Date
October 2008 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Charite University, Berlin, Germany
4. Oversight
5. 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.
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Metabolic Syndrome, Impaired Glucose Tolerance
Keywords
11ß-hydroxysteroid dehydrogenase, rosiglitazone, insulin sensitivity, Impaired glucose tolerance
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
24 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Rosiglitazone treatment
Arm Type
Experimental
Arm Description
Rosiglitazone will be given to the subjects. All subjects will be analyzed before and after treatment
Intervention Type
Drug
Intervention Name(s)
rosiglitazone
Other Intervention Name(s)
Avandia
Intervention Description
89 mg BID for 8 weeks, orally
Primary Outcome Measure Information:
Title
changes of 11ß-HSD1 expression in adipose tissue and skeletal muscle during 8 weeks of rosiglitazone treatment
Description
11ß-HSD1 expression will be measured in adipose tissue and skeletal muscle
Time Frame
8 weeks
Title
changes of hepatic 11ß-HSD1 activity during 8 weeks of rosiglitazone treatment
Description
11ß-HSD1 activity will be assessed by measuring conversion of cortisone to cortisol (ratio will be calculated)
Time Frame
8 weeks
Title
changes of whole body 11ß-HSD1 activity during 8 weeks of rosiglitazone treatment
Description
whole body 11ß-HSD1 activity will be assessed by measuring the ratio of urinary tetrahydrocortisol (THF) + alpha-tetrahydrocortisol (THF) / tetrahydrocortisone
Time Frame
8 weeks
Secondary Outcome Measure Information:
Title
changes in insulin sensitivity during 8 weeks of rosiglitazone treatment
Description
Measurement of whole body and myocellular insulin sensitivity (mg•kg-1•min-1/(mU•L-1)) before and after treatment
Time Frame
8 weeks
Title
Hormonal and metabolic changes induced by the intervention
Description
Whole body as well as tissue specific (skeletal muscle and different adipose tissue compartment) changes in hormonal circuits and metabolism will be analyzed
Time Frame
3 months
Title
changes of FGF-21 induced by the intervention
Description
FGF-21 (ng/ml) will be assessed in plasma samples
Time Frame
8 weeks
Title
changes of free fatty acids (FFA) induced by the intervention
Description
FFA (mmol/l) will be assessed in plasma samples
Time Frame
8 weeks
Title
changes of myocellular SCD1 expression induced by the intervention
Description
myocellular SCD1 mRNA expression will be assessed
Time Frame
8 weeks
Title
changes of myocellular long chain fatty acids (LC-FA) expression induced by the intervention
Description
myocellular LC-FA mRNA expression will be assessed
Time Frame
8 weeks
10. Eligibility
Sex
All
Minimum Age & Unit of Time
20 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Knut Mai
Organizational Affiliation
Charite, Dpt. of Endocrinology, Diabetes and Nutrition
Official's Role
Principal Investigator
Facility Information:
Facility Name
Charite, Campus Benjamin Franklin
City
Berlin
ZIP/Postal Code
12200
Country
Germany
12. IPD Sharing Statement
Citations:
PubMed Identifier
21741058
Citation
Mai K, Andres J, Bobbert T, Assmann A, Biedasek K, Diederich S, Graham I, Larson TR, Pfeiffer AF, Spranger J. Rosiglitazone increases fatty acid Delta9-desaturation and decreases elongase activity index in human skeletal muscle in vivo. Metabolism. 2012 Jan;61(1):108-16. doi: 10.1016/j.metabol.2011.05.018. Epub 2011 Jul 7.
Results Reference
derived
Learn more about this trial
11ß-HSD1 and Metabolic Syndrome
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