Clinical Trial: Effect of Cortisol on Physical Exertion in Patients With Primary Adrenal Failure

Study Status: Completed
Recruit Status: Unknown status
Study Type: Interventional

Official Title: Effect of Cortisol on Physical Exertion in Patients With Primary Adrenal

Brief Summary: The conventional glucocorticoid replacement therapy in primary adrenal insufficiency- Addison's disease,renders the cortisol levels unphysiological, which may cause symptoms and long-term complications. Many patients take stress-doses that are extra doses of hydrocortisone or cortisone acetate before or during stressful physical or psychological events. However, the effect of such dosing has not been tested in scientific studies. In this double blind cross-over designed pilot trial we aim to test the effect of an extra dose of cortisol on physical activity and hormone levels.

Detailed Summary:

Addison's disease occurs when more than 90% of the adrenal cortex is destroyed. Cortisol levels in serum vary throughout the day. In addition to the daily need, cortisol increases in response to all forms of stress including intercurrent illness. The Addison patient must in such situations increase replacement doses 2 to 3-fold. While it is broad agreement on this procedure based on clinical experience and empirical data, it is controversial as to whether there is a need to increase the dose by less stressful events and tasks, such as average to vigorous physical activity and mental stress. In any event, many patients report that they benefit from stress doses not only in order to increase performance, but also to reduce post-exertion fatigue.

Using a combination of oxygen uptake measurements under controlled exercise and assay of hormones and metabolites, we aim to test whether extra doses of hydrocortisone can increase physical capacity and reduce post-exertion fatigue. Each patient perform two tests, one with and one without hydrocortisone in randomised order. The controls perform one test. The patients will be assigned a participation number and randomised to any of two treatment sequences (A-B or B-A) by pharmacy. All exercise tests will be performed 3-5 hours after intake of morning medication, after an overnight fast (water permitted). Patients will be instructed to avoid caffeinated food and drink, alcohol, strenuous exercise and starvation for at least 24h before each exercise session. Patients will be instructed to avoid smoking, brush teeth one hour before exercise testing.

One hour before each test, subjects drink one teaspoon of water per kilogram body weight to provide adequate hydration. Stress-dose or placebo will be taken 60 min before start. Also at this time, an indwelling line will be placed in the fore
Sponsor: Haukeland University Hospital

Current Primary Outcome: O2 uptake [ Time Frame: 2 days ]

O2 uptake as V O2 90%.


Original Primary Outcome: Same as current

Current Secondary Outcome:

  • post- exercise hypoglycemic events [ Time Frame: 4 days ]
    blood glucose below ≤ 3.1 mmol ⁄ L
  • glycemic variability [ Time Frame: 6 days ]
    glycemic variability monitored by continuous glucose monitoring system
  • hormone response to exercise [ Time Frame: 2 days ]
    • Plasma norepinephrine, epinephrine, salivary alfa amylase
    • Glucose, insulin, C-peptide, and lactate, glucagon
    • Growth hormone and insulin like growth factor
    • Free fatty acids
  • Blood pressure [ Time Frame: 2 days ]
    vascular action
  • Subjective health status [ Time Frame: 2 days ]
    Self administration by questionnaires


Original Secondary Outcome: Same as current

Information By: Haukeland University Hospital

Dates:
Date Received: April 23, 2013
Date Started: June 2013
Date Completion: March 2014
Last Updated: November 29, 2013
Last Verified: November 2013