The Effects of TZD on Fat Metabolism and Insulin Sensitivity in GH-Replaced GHD Patients

This study has been completed.
Sponsor:
Information provided by:
University of Aarhus
ClinicalTrials.gov Identifier:
NCT00459940
First received: April 12, 2007
Last updated: NA
Last verified: April 2007
History: No changes posted
  Purpose

In the present double blind, placebo-controlled, parallel study we evaluated the impact of 12 weeks thiazolidinedione (TZD) administration on basal and insulin-stimulated substrate metabolism in growth hormone-replaced adults with growth hormone deficiency.


Condition Intervention
Growth Hormone Deficiency
Drug: Pioglitazone

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double-Blind
Primary Purpose: Treatment
Official Title: "Can Growth Hormone's Lipolytic and Insulin-Antagonistic Effects be Modified by Peroxisome Proliferator-Activated Gamma Agonists?"

Resource links provided by NLM:


Further study details as provided by University of Aarhus:

Primary Outcome Measures:
  • Circulating FFA level
  • FFA turnover
  • Lipid oxidation

Estimated Enrollment: 20
Study Start Date: September 2004
Study Completion Date: March 2006
Detailed Description:

In human subjects GH (Growth Hormone) acutely antagonises the effects of insulin on glucose uptake in skeletal muscle and increases the hepatic glucose production of humans. This has clinical implications for patients with active acromegaly, in whom the prevalence of glucose intolerance and overt diabetes mellitus is increased. It is also of significance in relation to GH replacement therapy in GH-deficient adults not least when considering that a substantial proportion of these patients are insulin resistant in the GH-untreated state. There is evidence to indicate that the acute insulin antagonistic effects may be balanced with time by the favourable effects of GH on body composition and physical fitness, but the data are ambiguous. The mechanism underlying these effects of GH are not fully characterised, but there is experimental evidence of a causal linked to the concomitant stimulation of lipolysis, since GH-induced insulin resistance is partly abrogated when lipolysis is pharmacologically suppressed. This is noteworthy since elevated levels of free fatty acids (FFA) are also implicated in the pathogenesis of insulin resistance in patients with the metabolic syndrome and type 2 diabetes mellitus. Thiazolidinediones (TZDs) are insulin sensitizers which function as highaffinity agonists for the nuclear peroxisome-proliferator-activated receptor (PPAR) gamma, which improve insulin sensitivity in T2DM. PPAR gamma is a nuclear receptor expressed mainly in adipocytes, which activates the transcription of genes involved in lipid and glucose metabolism. Administration of TZD in T2DM enhances insulin-stimulated glucose uptake via mechanisms including a lowering of circulating FFA and a redistribution of fat away from hepatocytes and myocytes and into peripheral adipocytes. To our knowledge, the impact of TZDs on GH-induced insulin resistance has not previously been reported. Experimental data in human subjects on this issue are of potential importance not only in relation to patients with abnormal GH status, but also regarding our understanding of the pathogenesis of insulin resistance in general and the complex actions of PPAR gamma activation in particular.

  Eligibility

Ages Eligible for Study:   19 Years to 71 Years
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Growth hormone replaced (minimum 6 months) growth hormone deficient men
  • Age over 18 years

Exclusion Criteria:

  • Ischemic coronary disease, defined by EF<0.6, former myocardial infarction, angina pectoris or actual treatment of cardiac insufficiency
  • Actual or former malignancy, except intracranial neoplasia that caused the participants pituitary disease, provided that there was clinical evidence for permanent remission
  • Blood donation within 6 months
  • Excessive alcohol consumption
  • Known allergic reaction from contents of test drug
  • Radioactive radiation exposure in terms of treatment or study enrollment within one year
  • Liver insufficiency
  • Insulin treatment
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00459940

Locations
Denmark
Medical Department M, The Medical Research Laboratories, Aarhus University Hospital
Aarhus C, Denmark, 8000
Sponsors and Collaborators
University of Aarhus
Investigators
Principal Investigator: Jens OL Jorgensen, MD University of Aarhus
  More Information

Publications:
ClinicalTrials.gov Identifier: NCT00459940     History of Changes
Other Study ID Numbers: 20030288
Study First Received: April 12, 2007
Last Updated: April 12, 2007
Health Authority: Denmark: Danish Medicines Agency
Denmark: Danish Dataprotection Agency

Keywords provided by University of Aarhus:
Growth hormone
Lipolysis
Insulin resistance
Pioglitazone
Growth hormone replaced growth hormone deficient adults

Additional relevant MeSH terms:
Dwarfism, Pituitary
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
Endocrine System Diseases
Pioglitazone
Insulin
Hormones
Hypoglycemic Agents
Physiological Effects of Drugs
Pharmacologic Actions
Hormones, Hormone Substitutes, and Hormone Antagonists

ClinicalTrials.gov processed this record on September 18, 2014