Growth Hormone and Glucose Metabolism
Information source: Charite University, Berlin, Germany
ClinicalTrials.gov processed this data on August 23, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Growth Hormone Deficiency
Intervention: recombinant human Growth Hormone (Genotropin® ) (Drug)
Phase: Phase 4
Status: Completed
Sponsored by: Charite University, Berlin, Germany Official(s) and/or principal investigator(s): Ayman M Arafat, Dr.med., Principal Investigator, Affiliation: Charite Campus Benjamin Franklin
Summary
The aim of the study is to investigate changes in insulin sensitivity and ß-cell function
after 24 and 48 weeks of low-dose growth hormone (GH) therapy in adult patients with severe
GH deficiency using highly standardized techniques. Insulin sensitivity was estimated using
euglycemic, hyperinsulinemic clamps, while insulin secretion and hepatic insulin clearance
were determined by changes in insulin and C-peptide levels during hyperglycemic
hyperinsulinemic clamps with consecutive intravenous (i. v.) L-arginine stimulation tests.
Moreover, the researchers investigated changes in body composition, lipolysis and
cardiovascular risk markers. Furthermore, in order to verify the mechanisms involved in the
pathogenesis of GH-induced insulin resistance and the GH-induced improvement in insulin
resistance under long term treatment, the researchers intend to establish changes in
intramyocellular lipid (IMCL) in patients with GH deficiency by magnetic resonance
(MR)-spectroscopy before and during GH-treatment and to correlate IMCL with insulin
resistance, insulin secretion and insulin clearance. Finally, the researchers aim to justify
the effect of GH on adiponectin secretion as well as on the 11-ß hydroxylase activity.
Clinical Details
Official title: Effects of Treatment With Human Growth Hormone on Insulin Resistance and Insulin Secretion in Adults With Growth Hormone Deficiency
Study design: Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Basic Science
Primary outcome: Change from baseline in insulin sensitivity after 24 and 48 weeks of treatment with low GH dose in severely GH deficient patients.
Secondary outcome: Changes from baseline in insulin secretion and insulin clearance, as well as changes in body composition, lipolysis, cardiovascular risk markers, Adiponectin, IMCL and 11ßHSD activity.
Detailed description:
In adult patients with GH deficiency, it is well documented that treatment with recombinant
human GH results in a reduction of visceral fat mass and an increase in muscle mass. During
long-term treatment, these effects seem to have beneficial effects on glucose metabolism.
However, during the initial phase of GH treatment the insulin antagonistic effect of GH
often induces an insulin resistant state which leads to an increase in insulin secretion or
even, in cases with a preexisting ß-cell defect, to overt diabetes. Due to the lipolytic
effect of GH, an impact of GH treatment on intracellular lipid homeostasis in adipose
tissue, but also in skeletal muscle cells and liver cells can be expected. Moreover, since
insulin resistance is known to be closely correlated with intramyocellular lipid (IMCL)
content, changes in IMCL can play a key role in the GH-induced changes in the insulin
sensitivity. Anyway, the mechanisms involved in the pathogenesis of GH-induced insulin
resistance and the GH-induced improvement in insulin resistance under long term treatment
are presently not fully understood. In order to verify these mechanisms, we intend to
establish changes in IMCL in patients with GH deficiency by MR-spectroscopy before and
during GH-treatment and to correlate IMCL with insulin resistance, insulin secretion and
insulin clearance. Finally, we aim to justify the effect of GH on adiponectin secretion as
well as on the 11-ß hydroxylase activity.
Eligibility
Minimum age: 18 Years.
Maximum age: N/A.
Gender(s): Both.
Criteria:
Inclusion Criteria:
- Patients >18 years old.
- Severe GH deficiency as diagnosed by an inadequate GH stimulation in three different
tests:
1. peak response < 3 µg/l during an insulin tolerance test;
2. < 3 µg/l during glucagon test;
3. < 9 µg/l during GHRH-arginine stimulation test).
Exclusion Criteria:
- GH replacement therapy prior to inclusion.
- History of diabetes Type 1 or 2.
- Biochemical evidence of impaired hepatic or renal function.
- History of cardiovascular disease.
- Uncontrolled hypertension.
- Current inflammatory or malignant disease.
- Pregnancy.
Locations and Contacts
Charite Campus Benjamin Franklin, Berlin 12200, Germany
Additional Information
Growth hormone therapy
Starting date: November 2003
Last updated: June 29, 2009
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