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

Phase 4

Completed

Conditions: Adrenal Insufficiency

Interventions: Drug: Hydrocortisone

Registration Number: NCT01546922

Lead Sponsor: University Medical Center Groningen

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 Description: * 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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 63

Inclusion Criteria

Patients with secondary adrenal insufficiency.
Age ≥ 18 - 75 years
≥ One year after tumor treatment with surgery and/or radiotherapy
On stable concomitant medications for at least six months prior to entry of study
Body weight 50-100 kg

Exclusion Criteria

Inability of legal consent
Documented cognitive impairment
Drug abuse/dependence
History of / current psychiatric disorders
Use of anti-epileptics (e.g. carbamezapine)
Cushing Disease
Type 1 diabetes or Type 2 diabetes with medication known to induce hypoglycemia (f.e. Sulfonylurea derivatives
Current treatment for second malignancy
Have a significant medical condition (e.g. hepatic, respiratory, or cardiovascular) which, in the opinion of the investigator, may interfere with the interpretation of results and safety or efficacy evaluations.
A history of frequent hypocortisolism
Hospitalization during study
Work in shifts

Study & Design

Study Type: INTERVENTIONAL

Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
First low dose HC followed by high dose HC	Hydrocortisone	First low dose of hydrocortisone = 0.2-0.3 mg/kg body weight for 10 weeks followed by a high dose of hydrocortisone = 0.4-0.6 mg/kg body weight
First high dose HC followed by low dose HC	Hydrocortisone	First a high dose of hydrocortisone = 0.4-0.6 mg/kg body weight for 10 weeks followed by a low dose of hydrocortisone = 0.2-0.3 mg/kg body weight

Primary Outcome Measures

Name	Time	Method
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.	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).	Cognitive domains to be tested: memory, executive functioning, attention and social cognition. The psychological tests consist of oral and written questions or computer tasks. Data is given as Z-scores based on normative data. Higher Z-scores represent a better performance.

Secondary Outcome Measures

Name	Time	Method
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.	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.	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.	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.	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.