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

Adrenal Insufficiency Clinical Trial

— 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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01546922
• Other study ID #: NL 35668.042.11
• Secondary ID: 2011-000864-82
• Status: Completed
• Phase: Phase 4
• First received: February 7, 2012
• Last updated: June 10, 2014
• Start date: February 2012
• Est. completion date: June 2013

Study information

• Verified date: June 2014
• Source: University Medical Center Groningen
• Contact: n/a
• Is FDA regulated: No
• Health authority: Netherlands: Medical Ethics Review Committee (METC)Netherlands: Dutch Health Care Inspectorate
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 63
• Est. completion date: June 2013
• Est. primary completion date: June 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 75 Years

Eligibility

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

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

Related Conditions & MeSH terms

• Adrenal Insufficiency

Intervention

Drug:
• Hydrocortisone
Patients 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.

Locations

Country	Name	City	State
Netherlands	University Medical Centre Groningen	Groningen

Sponsors (1)

Lead Sponsor	Collaborator
University Medical Center Groningen

Country where clinical trial is conducted

Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	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.	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).	No
Secondary	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.	Quality of life questionnaires have to be filled in by the participant at his/her home place and have to be returned by post.	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).	No
Secondary	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.	Cardiovascular and metabolic risk factors, (pituitary) hormones and bone markers.	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).	No
Secondary	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.	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.	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).	No
Secondary	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.	The patients report common somatic complaints by filling in structured daily diaries.	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).	No