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

Primary Purpose

Adrenal Insufficiency

Status
Completed
Phase
Phase 4
Locations
Netherlands
Study Type
Interventional
Intervention
Hydrocortisone
Sponsored by
University Medical Center Groningen
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Adrenal Insufficiency focused on measuring Hydrocortisone, Cognition, Adrenal insufficiency, Quality of Life, Common Somatic Complaints, Cardiovascular/Metabolic Profile, Somatosensation

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • University Medical Centre Groningen

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Active Comparator

Arm Label

First low dose HC followed by high dose HC

First high dose HC followed by low dose HC

Arm Description

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 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

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.
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.
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.
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.

Full Information

First Posted
February 7, 2012
Last Updated
June 10, 2014
Sponsor
University Medical Center Groningen
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1. Study Identification

Unique Protocol Identification Number
NCT01546922
Brief Title
Hydrocortisone Replacement in Patients With Secondary Adrenal Insufficiency (SUPREME CORT)
Acronym
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

2. Study Status

Record Verification Date
June 2014
Overall Recruitment Status
Completed
Study Start Date
February 2012 (undefined)
Primary Completion Date
June 2013 (Actual)
Study Completion Date
June 2013 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University Medical Center Groningen

4. Oversight

Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Adrenal Insufficiency
Keywords
Hydrocortisone, Cognition, Adrenal insufficiency, Quality of Life, Common Somatic Complaints, Cardiovascular/Metabolic Profile, Somatosensation

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Crossover Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
63 (Actual)

8. Arms, Groups, and Interventions

Arm Title
First low dose HC followed by high dose HC
Arm Type
Active Comparator
Arm Description
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
Arm Title
First high dose HC followed by low dose HC
Arm Type
Active Comparator
Arm Description
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
Intervention Type
Drug
Intervention Name(s)
Hydrocortisone
Intervention Description
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.
Primary Outcome Measure Information:
Title
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.
Description
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.
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).
Secondary Outcome Measure Information:
Title
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.
Description
Quality of life questionnaires have to be filled in by the participant at his/her home place and have to be returned by post.
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).
Title
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.
Description
Cardiovascular and metabolic risk factors, (pituitary) hormones and bone markers.
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).
Title
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.
Description
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.
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).
Title
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.
Description
The patients report common somatic complaints by filling in structured daily diaries.
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).

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
André P van Beek, Dr.
Organizational Affiliation
University Medical Center Groningen
Official's Role
Principal Investigator
Facility Information:
Facility Name
University Medical Centre Groningen
City
Groningen
ZIP/Postal Code
9700RB
Country
Netherlands

12. IPD Sharing Statement

Citations:
PubMed Identifier
29982583
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.
Results Reference
derived
PubMed Identifier
28521880
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.
Results Reference
derived
PubMed Identifier
27490921
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.
Results Reference
derived
PubMed Identifier
26646751
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.
Results Reference
derived
PubMed Identifier
25705800
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.
Results Reference
derived

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

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