Clinical trial NCT01546922: Hydrocortisone Replacement in Patients With Secondary Adrenal Insufficiency (SUPREME CORT)
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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Adrenal Insufficiency
Keywords: Hydrocortisone
Cognition
Adrenal insufficiency
Quality of Life
Common Somatic Complaints
Cardiovascular/Metabolic Profile
Somatosensation
Lead sponsor: University Medical Center Groningen
Sponsor class: OTHER
First posted: 2012-03-07
Enrollment: 63
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

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.

Eligibility 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

Primary outcomes:
measure: 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.
timeFrame: 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).
Secondary outcomes:
measure: 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.
timeFrame: 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).
measure: 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.
timeFrame: 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).
measure: 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.
timeFrame: 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).
measure: 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.
timeFrame: 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).
Other outcomes:
Locations:
city: Groningen
country: Netherlands
facility: University Medical Centre Groningen
Study officials:
affiliation: University Medical Center Groningen
name: André P van Beek, Dr.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Sorgdrager FJH, Werumeus Buning J, Bos EH, Van Beek AP, Kema IP. Hydrocortisone Affects Fatigue and Physical Functioning Through Metabolism of Tryptophan: A Randomized Controlled Trial. J Clin Endocrinol Metab. 2018 Sep 1;103(9):3411-3419. doi: 10.1210/jc.2018-00582.
citation: Werumeus Buning J, Touw DJ, Brummelman P, Dullaart RPF, van den Berg G, van der Klauw MM, Kamp J, Wolffenbuttel BHR, van Beek AP. Pharmacokinetics of oral hydrocortisone - Results and implications from a randomized controlled trial. Metabolism. 2017 Jun;71:7-16. doi: 10.1016/j.metabol.2017.02.005. Epub 2017 Feb 13.
citation: Werumeus Buning J, van Faassen M, Brummelman P, Dullaart RP, van den Berg G, van der Klauw MM, Kerstens MN, Stegeman CA, Muller Kobold AC, Kema IP, Wolffenbuttel BH, van Beek AP. Effects of Hydrocortisone on the Regulation of Blood Pressure: Results From a Randomized Controlled Trial. J Clin Endocrinol Metab. 2016 Oct;101(10):3691-3699. doi: 10.1210/jc.2016-2216. Epub 2016 Aug 4.
citation: Werumeus Buning J, Brummelman P, Koerts J, Dullaart RP, van den Berg G, van der Klauw MM, Sluiter WJ, Tucha O, Wolffenbuttel BH, van Beek AP. Hydrocortisone Dose Influences Pain, Depressive Symptoms and Perceived Health in Adrenal Insufficiency: A Randomized Controlled Trial. Neuroendocrinology. 2016;103(6):771-8. doi: 10.1159/000442985. Epub 2015 Dec 9.
citation: Werumeus Buning J, Brummelman P, Koerts J, Dullaart RP, van den Berg G, van der Klauw MM, Tucha O, Wolffenbuttel BH, van Beek AP. The effects of two different doses of hydrocortisone on cognition in patients with secondary adrenal insufficiency--results from a randomized controlled trial. Psychoneuroendocrinology. 2015 May;55:36-47. doi: 10.1016/j.psyneuen.2015.02.001. Epub 2015 Feb 10.