Clinical Trial: The Influence of Different Hydrocortisone Replacement Doses on the Partitioning and Flexibility of Ectopic Lipids in Patients With Corticotropic Hypopituitarism

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional

Official Title: The Influence of Different Hydrocortisone Replacement Doses on the Partitioning and Flexibility of Ectopic Lipids (Intrahepatocellular IHCL and Intramyocellular IMCL) in Patients With Corticotropic

Brief Summary: This study aims at assessing the effect of today's standard of hydrocortisone dosage versus previous hydrocortisone dosage on flexibility and partitioning of ectopic lipid depots (IMCL and IHCL) after a standardised fat load followed by a short-term aerobic exercise in patients with corticotropic pituitary insufficiency.

Detailed Summary:

Background

The investigators and others have shown that long-term hydrocortisone replacement therapy at higher doses of hydrocortisone replacement therapy at higher doses of hydrocortisone replacement (as previously recommended) is associated with higher mortality. The pathophysiology for the association of hydrocortisone-replacement dose and mortality remains unclear. A possible underlying mechanism is nonalcoholic fatty liver disease which is more prevalent in patients with hypopituitarism. Patients with non-alcoholic fatty liver disease are at a higher risk for overall-mortality.

It remains to be established whether the insulin resistance, associated with increased intrahepatocellular lipids and increased intramusculoskeletal lipids, is implicated in the pathophysiology of these epidemiological findings.

Interestingly, it has been shown that a reduction of hydrocortisone replacement dose from 20-30mg/d to 10-15mg/d resulted in a loss of body fat and a significant decrease of plasma total cholesterol and triglyceride concentration. The effect of IMCL and IHCL is so far unknown.

Patients with hypopituitarism with hydrocortisone replacement therapy provide a unique disease model to study the short-term effects of previously recommended dose (higher dose) of hydrocortisone versus lower dose of HC replacement therapy on ectopic lipids (IMCL; IHCL) lipids, as well as on subcutaneous and visceral fat mass and on parameters of insulin resistance. Combining MRI and MR-spectroscopy techniques, different fat mass (subcutaneous and visceral) and ectopic lipids can be repeatedly and non-invasively assessed.

Objective

To investigate the
Sponsor: University Hospital Inselspital, Berne

Current Primary Outcome:

  • Change from baseline in flexibility of Intramyocellular Lipids (IMCL) Measured in mmol/L [ Time Frame: 3 months ]
    Measured in mmol/L
  • Change from baseline in flexibility of Intrahepatocellular Lipids (IHCL) Measured in mmol/L [ Time Frame: 3 months ]
    Measured in mmol/L


Original Primary Outcome: Same as current

Current Secondary Outcome:

  • Free Fatty Acids (FFA) availability during exercise before and after additional hydrocortisone/placebo Measured in mmol/L [ Time Frame: At baseline, 3 months ]
    Measured in mmol/L
  • Flexibility of ectopic fat stores, defined as difference between intramyocellular/intrahepatocellular lipid concentration before and after exercise, and their possible relation to insulin sensitivity before and after additional hydrocortisone/placebo [ Time Frame: At baseline, 3 months ]
  • Free Fatty Acids (FFA) availability during exercise and the possible relation to insulin sensitivity before and after additional hydrocortisone/placebo Measured in mmol/L [ Time Frame: At baseline, 3 months ]
    Measured in mmol/L
  • Effect of exercise on insulin at baseline [ Time Frame: At baseline ]
  • Effect of exercise on insulin at 3 months [ Time Frame: 3 months ]
  • Effect of exercise on catecholamines at baseline [ Time Frame: At baseline ]
  • Effect of exercise on catecholamines at 3 months [ Time Frame: 3 months ]
  • Effect of exercise on growth hormone at baseline [ Time Frame: At baseline ]
  • Effect of exercise on growth hormone at 3 months [ Time Frame: 3 months ]
  • Effect of exercise on cortisol at baseline [ Time Frame: At baseline ]
  • Effect of exercise on cortisol at 3 months [ Time Frame: 3 months ]
  • Effect of exercise on lactate at baseline [ Time Frame: At baseline ]
  • Effect of exercise on lactate at 3 months [ Time Frame: 3 months ]
  • Effect of exercise on glucose at baseline [ Time Frame: At baseline ]
  • Effect of exercise on glucose at 3 months [ Time Frame: 3 months ]
  • Effect of exercise on inflammatory markers at baseline [ Time Frame: At baseline ]
  • Effect of exercise on inflammatory markers at 3 months [ Time Frame: 3 months ]


Original Secondary Outcome: Same as current

Information By: University Hospital Inselspital, Berne

Dates:
Date Received: January 16, 2015
Date Started: January 2015
Date Completion: December 2016
Last Updated: August 19, 2015
Last Verified: August 2015