Growth Hormone and Glucose Metabolism (GHGMS)

This study has been completed.
Sponsor:
Information provided by:
Charite University, Berlin, Germany
ClinicalTrials.gov Identifier:
NCT00929799
First received: June 29, 2009
Last updated: NA
Last verified: June 2009
History: No changes posted
  Purpose

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.


Condition Intervention Phase
Growth Hormone Deficiency
Drug: recombinant human Growth Hormone (Genotropin® )
Phase 4

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Basic Science
Official Title: Effects of Treatment With Human Growth Hormone on Insulin Resistance and Insulin Secretion in Adults With Growth Hormone Deficiency

Resource links provided by NLM:


Further study details as provided by Charite University, Berlin, Germany:

Primary Outcome Measures:
  • Change from baseline in insulin sensitivity after 24 and 48 weeks of treatment with low GH dose in severely GH deficient patients. [ Time Frame: At 24 and 48 weeks of treatment ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • 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. [ Time Frame: At 24 and 48 weeks of treatment ] [ Designated as safety issue: No ]

Enrollment: 6
Study Start Date: November 2003
Study Completion Date: August 2007
Primary Completion Date: August 2007 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Growth Hormone
Therapy with recombinant human GH (Genotropin® 1 mg = 3 IU, Pfizer Inc., NY, USA) daily by subcutaneous injection using a Genotropin pen at maximal GH dose of 0.003 mg/kg/day in patients with severe GHD
Drug: recombinant human Growth Hormone (Genotropin® )
Once daily by subcutaneous injection using a Genotropin pen in the abdomen at 22:00 h. Maximal GH dose of 0.003 mg/kg/day.

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

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT00929799

Locations
Germany
Charite Campus Benjamin Franklin
Berlin, Germany, 12200
Sponsors and Collaborators
Charite University, Berlin, Germany
Investigators
Principal Investigator: Ayman M Arafat, Dr.med. Charite Campus Benjamin Franklin
  More Information

Additional Information:
No publications provided by Charite University, Berlin, Germany

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Dr. med AYMAN M. ARAFAT, Charité-University Medicine Berlin
ClinicalTrials.gov Identifier: NCT00929799     History of Changes
Other Study ID Numbers: NRA 6280012, EK218-01
Study First Received: June 29, 2009
Last Updated: June 29, 2009
Health Authority: Germany: Federal Institute for Drugs and Medical Devices

Additional relevant MeSH terms:
Dwarfism, Pituitary
Endocrine System Diseases
Dwarfism
Bone Diseases, Developmental
Bone Diseases
Musculoskeletal Diseases
Bone Diseases, Endocrine
Hypopituitarism
Pituitary Diseases
Hypothalamic Diseases
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on July 22, 2014