Growth Hormone and Glucose Metabolism (GHGMS)

June 29, 2009 updated by: Charite University, Berlin, Germany

Effects of Treatment With Human Growth Hormone on Insulin Resistance and Insulin Secretion in Adults With Growth Hormone Deficiency

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

6

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Germany
      • Berlin, Germany, 12200
        • Charite Campus Benjamin Franklin

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Basic Science
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
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
At 24 and 48 weeks of treatment

Secondary Outcome Measures

Outcome Measure
Time Frame
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
At 24 and 48 weeks of treatment

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Charite University, Berlin, Germany

Investigators

  • Principal Investigator: Ayman M Arafat, Dr.med., Charite Campus Benjamin Franklin

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

November 1, 2003

Primary Completion (Actual)

August 1, 2007

Study Completion (Actual)

August 1, 2007

Study Registration Dates

First Submitted

June 29, 2009

First Submitted That Met QC Criteria

June 29, 2009

First Posted (Estimate)

June 30, 2009

Study Record Updates

Last Update Posted (Estimate)

June 30, 2009

Last Update Submitted That Met QC Criteria

June 29, 2009

Last Verified

June 1, 2009

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • NRA 6280012
  • EK218-01

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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