Testosterone and Lipolysis, Insulin Sensitivity and Protein Metabolism

NCT00613288 | Completed

• 1 other identifier: M-20070046
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief Summary

Testosterone(T) has known effects on many organ systems, although many of its metabolic actions are unrevealed. T is an anabolic hormone stimulating protein synthesis but this effect has barely been investigated in controlled studies. It also has lipolytic actions influencing body composition, but little is known of its regional impact on fat tissue. T affects insulin sensitivity. There is an increased incidence of hypogonadism in type 2 diabetes, and among patients with hypogonadism there is an increased incidence of type 2 diabetes. The actions of testosterone on glucose metabolism are unknown. The purpose of this study is therefore to: Investigate the lipolytic effect of testosterone on muscle and fat tissue. To gain insight in the intracellular mechanisms of testosterone on lipolysis and investigate possible regional differences in lipolysis and changes in body composition. Finally to investigate the effect of short term experimental hypogonadism and acute testosterone substitution on cytokines, insulin sensitivity and protein metabolism. The trial is a randomised double blinded cross-over study of 4 x 2 days with an interval of 1 month in between. 12 healthy young men will receive GnRH treatment over a 3 month period and examined on 4 occasions with various degrees of T substitution and placebo . The examinations take place at the Research Lab within the Medical Department M. The investigations are deemed relevant to the understanding of the interrelationship between male hypogonadism and type 2 diabetes. The hypothesis is that T has beneficial effects on carbohydrate, fat and protein metabolism. The generated knowledge would therefore hopefully improve prophylaxis, screening and early treatment of both group of patients.

Conditions

Hypogonadism

Keywords

acute; testosterone; experimental; hypogonadism; lipolysis; insulin sensitivity; protein; metabolism; Experimental hypogonadism; Testosterone substitution

Outcome Measures

Primary Outcomes (1)

• Testosterone influence on Insulin Sensitivity, Lipolysis and protein metabolism

  4-6 month pr patient

Secondary Outcomes (1)

• Testosterone influence on Body composition by DEXA scan, Energy expenditure by indirect Calorimetry and VO2 max test

  4-6 month pr patient

Study Arms (1)

A

EXPERIMENTAL

Drug: Testosterone (Testogel), GnRH analog (Leuprorelide) and Placebo

Interventions

Testosterone (Testogel), GnRH analog (Leuprorelide) and Placebo DRUG

The trial is a double blinded, randomised cross-over study of 4 x 2 days with an interval of 1 month in between. 12 healthy young male participants will receive the GnRH-agonist leuprorelide 7,5 mg s.c. 3 weeks before examination on 3 occasions, and a fourth day without intervention. The four days will include treatment on the examination day, Day 1 with: 1. Placebo (hypogonadism after leuprorelide injection) 2. Testosterone gel 50 mg applicated in the morning at 06.00 am (physiologic substitution - after leuprorelide injection). 3. Testosterone gel 150 mg applicated in the morning at 06.00 am (supra-physiologic substitution - after leuprorelide injection). 4. No treatment.

A

Eligibility Criteria

• Age: 20 Years - 35 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Male, age 20-35
• Normal biochemical screen and ECG

You may not qualify if:

• Heart disease
• BMI\>25
• Diabetes
• Antecedent or present cancer
• Vascular disease
• Antecedent or present hormone treatment
• Medical treatment with known effects on fat metabolism
• Big X-ray examinations equivalent to, or more than a chest x-ray and all kinds of CT scans until 6 month before the start of the study and during the study.

Sponsors & Collaborators

• University of Aarhus: lead

Study Sites (1)

Medical department M and Investigational Laboratories

Aarhus C, Jutland, 8000, Denmark

Location

Related Publications (2)

• Malkin CJ, Pugh PJ, Jones RD, Kapoor D, Channer KS, Jones TH. The effect of testosterone replacement on endogenous inflammatory cytokines and lipid profiles in hypogonadal men. J Clin Endocrinol Metab. 2004 Jul;89(7):3313-8. doi: 10.1210/jc.2003-031069.

  PMID: 15240608 BACKGROUND

• Host C, Gormsen LC, Christensen B, Jessen N, Hougaard DM, Christiansen JS, Pedersen SB, Jensen MD, Nielsen S, Gravholt CH. Independent effects of testosterone on lipid oxidation and VLDL-TG production: a randomized, double-blind, placebo-controlled, crossover study. Diabetes. 2013 May;62(5):1409-16. doi: 10.2337/db12-0440. Epub 2012 Nov 27.

  PMID: 23193189 DERIVED

MeSH Terms

Conditions

Hypogonadism; Insulin Resistance

Interventions

Testosterone; Gonadotropin-Releasing Hormone

Condition Hierarchy (Ancestors)

Gonadal Disorders; Endocrine System Diseases; Hyperinsulinism; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Androstenols; Androstenes; Androstanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Testosterone Congeners; Gonadal Steroid Hormones; Gonadal Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Pituitary Hormone-Releasing Hormones; Hypothalamic Hormones; Peptide Hormones; Neuropeptides; Peptides; Amino Acids, Peptides, and Proteins; Oligopeptides; Nerve Tissue Proteins; Proteins

Study Officials

• Jens S Christensen, Professor

  Medical Department M, Aarhus University Hospital, Denmark

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: January 31, 2008
• First Posted: February 13, 2008
• Study Start: September 1, 2007
• Primary Completion: September 1, 2009
• Study Completion: September 1, 2009
• Last Updated: October 22, 2009

Record last verified: 2009-10

Locations

DK (1)