Clinical Trial: Hydrocortisone Replacement in Patients With Secondary Adrenal Insufficiency (SUPREME CORT)

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: A Randomized Double Blind Cross-over Study of the Effects of Low Dose and High Dose Hydrocortisone Replacement Therapy on Cognition, Quality of Life, Metabolic Profile and Somatosensation in Patients

Brief Summary: The aim of this study is to investigate whether a physiologically low hydrocortisone (HC) dose is better for cognition as compared to a physiologically high HC dose. In addition, quality of life, metabolic profile and somatosensation will be described in relation to HC dose.

Detailed Summary:

• Rationale: A wide variety in hydrocortisone (HC) substitution dose-regimens are considered physiological for patients with adrenal insufficiency. However, it is likely that cognition is negatively influenced by higher cortisol exposure to the brain. No studies have been performed to assess the effects of treatment regimens with a low physiological HC substitution dose on cognition in comparison to a high physiological HC substitution dose. These treatment regimens should take body weight and multiple dosing into account. In addition, substitution doses should be monitored by clinical evaluation and biochemical analysis for adverse effects associated with over- or under-replacement.
• Intervention: Patients with secondary adrenal insufficiency will be randomized in two groups to receive either a low dose HC (0.2-0.3 mg/kg body weight) for 10 weeks followed by 10 weeks of high dose HC (0.4-0.6 mg/kg body weight) or vice versa. At baseline and after both treatment periods, patients will be tested.

Sponsor: University Medical Center Groningen

Current Primary Outcome: Change in Cognition After 10 Weeks of Treatment With a Low Dose of Hydrocortisone Compared to 10 Weeks of Treatment With a High Dose of Hydrocortisone. [ Time Frame: After completion of treatment period 1 (that is after 10 weeks from baseline) and after treatment period 2 (that is after 20 weeks from baseline). ]

Original Primary Outcome: Cognitive performance. Impact of different doses of hydrocortisone on cognition, including a change on cognition with different doses. [ Time Frame: At baseline and after completion of treatment period 1 (that is after 10 weeks from baseline) and after treatment period 2 ( that is after 20 weeks from baseline). ]

Current Secondary Outcome:

• Change in Quality of Life After 10 Weeks of Treatment With a Low Dose of Hydrocortisone Compared to 10 Weeks of Treatment With a High Dose of Hydrocortisone. [ Time Frame: After completion of treatment period 1 (that is after 10 weeks from baseline) and after treatment period 2 (that is after 20 weeks from baseline). ]
  Quality of life questionnaires have to be filled in by the participant at his/her home place and have to be returned by post.
• Change in Metabolic Profile After 10 Weeks of Treatment With a Low Dose of Hydrocortisone Compared to 10 Weeks of Treatment With a High Dose of Hydrocortisone. [ Time Frame: After completion of treatment period 1 (that is after 10 weeks from baseline) and after treatment period 2 (that is after 20 weeks from baseline). ]
  Cardiovascular and metabolic risk factors, (pituitary) hormones and bone markers.
• Change in Somatosensation After 10 Weeks of Treatment With a Low Dose of Hydrocortisone Compared to 10 Weeks of Treatment With a High Dose of Hydrocortisone. [ Time Frame: After completion of treatment period 1 (that is after 10 weeks from baseline) and after treatment period 2 (that is after 20 weeks from baseline). ]
  Measures of somatosensation: the mechanical detection threshold, the mechanical pain threshold, mechanical pain sensitivity, dynamic mechanical allodynia, wind up ratio and the pressure pain threshold.
• Change in Perceived Common Somatic Complaints After 10 Weeks of Treatment With a Low Dose of Hydrocortisone Compared to 10 Weeks of Treatment With a High Dose of Hydrocortisone. [ Time Frame: during treatment period 1 (that is from week 1 to week 10 from baseline) and during treatment period 2 (that is from week 11 to week 20 from baseline). ]
  The patients report common somatic complaints by filling in structured daily diaries.

Original Secondary Outcome:

• Quality of life [ Time Frame: After 9 weeks from baseline and after 19 weeks from baseline. ]
  Quality of life questionnaires have to be filled in by the participant at his/her home place and have to be returned by post.
• Metabolic profile [ Time Frame: At baseline and after completion of treatment period 1 (that is after 10 weeks from baseline) and after treatment period 2 ( that is after 20 weeks from baseline). ]
  Cardiovascular and metabolic risk factors, (pituitary) hormones and bone markers.
• Somatosensations [ Time Frame: At baseline and after completion of treatment period 1 (that is after 10 weeks from baseline) and after treatment period 2 ( that is after 20 weeks from baseline). ]
  Measures of somatosensation: the mechanical detection threshold, the mechanical pain threshold, mechanical pain sensitivity, dynamic mechanical allodynia, wind up ratio and the pressure pain threshold.
• Common somatic complaints [ Time Frame: From the first day on study medication (that is the day after measurement 1) to the last day on study medication (that is the day before measurement 3). ]
  The patients have to fill in structured diaries regarding somatic complaints.

Information By: University Medical Center Groningen

Dates:
Date Received: February 7, 2012
Date Started: February 2012
Date Completion:
Last Updated: June 10, 2014
Last Verified: June 2014