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

Condition(s) targeted: Adrenal Insufficiency

Intervention: Hydrocortisone (Drug)

Phase: Phase 4

Status: Completed

Sponsored by: University Medical Center Groningen

Official(s) and/or principal investigator(s):
André P van Beek, Dr., Principal Investigator, Affiliation: University Medical Center Groningen

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.

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 With Secondary Adrenal Insufficiency

Study design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Crossover Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

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.

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.

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.

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.

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.

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.

Minimum age: 18 Years. Maximum age: 75 Years. Gender(s): Both.

Criteria:

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

University Medical Centre Groningen, Groningen 9700RB, Netherlands

Starting date: February 2012
Last updated: June 10, 2014