Hydrocortisone Replacement in Patients With Secondary Adr... | NCT01546922

ID	Type	Description	Link
2011-000864-82	EudraCT Number

Hydrocortisone Replacement in Patients With Secondary Adr... | NCT01546922 | Trialant

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
First low dose HC followed by high dose HC	Active Comparator	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	Drug: Hydrocortisone
First high dose HC followed by low dose HC	Active Comparator	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	Drug: Hydrocortisone

Interventions

Name	Type	Description	Arm Group Labels	Other Names
Hydrocortisone	Drug	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.

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
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).

Secondary Outcomes

Measure	Description	Time Frame
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).

Contacts/Locations Module

Name	Affiliation	Role
André P van Beek, Dr.	University Medical Center Groningen	Principal Investigator

Facility	Status	City	State	ZIP	Country	Contacts
University Medical Centre Groningen		Groningen	Provincie Groningen	9700RB	Netherlands

References Module

Citations

PubMed Identifier	Type	Citation	Retractions
29982583	Derived	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.
28521880	Derived	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.

Arm/Group Information

ID	Title	Description
FG000	First a Low Dose of HC Followed by a High Dose of HC	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
FG001	First a High Dose of HC Followed by a Low Dose of HC	First 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

Periods

Title

Milestones

Reasons Not Completed

First Period of 10 Weeks

Type	Comment	Milestone Data
STARTED		FG00030 subjects FG00130 subjects
COMPLETED		FG00025 subjects FG00128 subjects
NOT COMPLETED		FG0005 subjects FG0012 subjects

Type	Comment	Reasons
Protocol Violation		FG0003 subjects FG0011 subjects
Withdrawal by Subject		FG0001 subjects FG001

Second Period of 10 Weeks

Type	Comment	Milestone Data
STARTED		FG00025 subjects FG00128 subjects
COMPLETED		FG00022 subjects FG001

Baseline Characteristics Module

ID	Title	Description
BG000	All Participants	All participants completing both study periods

Units	Counts
Participants	BG000

Title	Description	Population Description	Parameter Type	Dispersion Type	Unit of Measure	Calculate Percentage	Denominator Units Selected	Denominators	Classes
Age, Continuous			Median

Outcome Measures Module

Outcome Measures

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

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.

The participants completing both study periods were analyzed

Posted

Mean

Standard Deviation

Z-scores based on normative data.

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).

ID	Title	Description
OG000	Low Dose of Hydrocortisone	Results from the participants while receiving the low dose of hydrocortisone

Adverse Events Module

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Low Dose of HC	Administration of a low dose of hydrocortisone (0.2-0.3 mg/kg body weight) for 10 weeks

Term	Organ System	Source Vocabulary	Assessment Type	Notes	Statistical Information
Influenza A infection	Infections and infestations		Systematic Assessment

Term	Organ System	Source Vocabulary	Assessment Type	Notes	Statistical Information
Influenza	Infections and infestations		Systematic Assessment

More Info Module

Certain Agreements

Title	Organization	Phone	Extension	Email
A. P. van Beek, MD PhD	University Medical Center Groningen	00315036110388		a.p.van.beek@umcg.nl

Condition Browse Module

ID	Term
D000309	Adrenal Insufficiency

ID	Term
D000307	Adrenal Gland Diseases
D004700	Endocrine System Diseases

Intervention Browse Module

ID	Term
D006854	Hydrocortisone

ID	Term
D011282	Pregnenediones
D011283	Pregnenes
D011278	Pregnanes
D013256	Steroids
D000072473

Type of radiotherapy

A total of 19 participants received radiotherapy

Number

participants

Title

Denominators

Categories

Pituitary radiotherapy

Title	Measurements
	BG00016

Cranial irradiation

Title	Measurements
	BG0002

Radiotherapy for extracranial tumors

Title	Measurements
	BG0001

Number of daily dosings prior to randomization

Number

participants

Title

Denominators

Categories

1 dose per day

Title	Measurements
	BG0003

2 doses per day

Title	Measurements
	BG00033

3 doses per day

Title	Measurements
	BG00011

Number of hormonal replacements

Number

participants

Title

Denominators

Categories

1 hormonal replacement

Title	Measurements
	BG0003

2 hormonal replacements

Title	Measurements
	BG0009

3 hormonal replacements

Title	Measurements
	BG00021

4 hormonal replacements

Title	Measurements
	BG00011

5 hormonal replacements

Title	Measurements
	BG0003

Sex hormone

Number

participants

Title

Denominators

Categories

Participants substituted

Title	Measurements
	BG00027

Men: testosterone substitution

Title	Measurements
	BG00023

Premenopausal women: estrogen substitution

Title	Measurements
	BG0004

Title

Denominators

Categories

RBMT-Immediate Memory

Title	Measurements
	OG000-0.41± 0.95 OG001-0.42± 1.33

RBMT-Delayed Memory

Title	Measurements
	OG0000.07± 0.98 OG0010.10± 1.33

RBMT-Delayed corrected for immediate memory

Title	Measurements
	OG0000.85± 1.09 OG0010.89± 1.34

15 Words Test-Short-term memory

Title	Measurements
	OG0000.36± 1.01 OG001-0.03± 1.03

15 Words Test-Total immediate memory

Title	Measurements
	OG0000.43± 1.02 OG0010.25± 0.92

15 Words Test - Learning Score

Title	Measurements
	OG0000.08± 1.05 OG0010.38± 1.19

15 Words Test - Delayed Memory

Title	Measurements
	OG0000.02± 1.04 OG0010.23± 0.97

15 Words Test - Delayed corrected for total memory

Title	Measurements
	OG000-0.30± 0.99 OG001-0.16± 0.99

15 Words Test-Recognition

Title	Measurements
	OG000-0.11± 0.88 OG0010.08± 0.71

Digit Span forward - Short term memory

Title	Measurements
	OG0000.49± 0.97 OG0010.56± 0.97

Rey Complex Figure - Immediate memory

Title	Measurements
	OG0001.14± 1.26 OG0011.40± 1.29

Rey Complex Figure - Delayed memory

Title	Measurements
	OG0001.11± 1.22 OG0011.28± 1.29

Divided attention-reaction time auditory response

Title	Measurements
	OG000-0.87± 0.81 OG001-0.89± 0.82

Divided attention-reaction time visual response

Title	Measurements
	OG000-0.06± 1.00 OG0010.03± 0.94

Divided attention - Number of omission errors

Title	Measurements
	OG000-0.02± 0.86 OG001-0.14± 0.93

Divided attention - Number of commission errors

Title	Measurements
	OG0000.30± 1.01 OG0010.34± 0.76

Visual scanning - Reaction time for target stimuli

Title	Measurements
	OG000-0.38± 1.04 OG001-0.36± 1.03

Visual scanning - Number of omission errors

Title	Measurements
	OG000-0.03± 1.06 OG0010.08± 1.08

Visual scanning - Number of commission errors

Title	Measurements
	OG000-0.72± 0.26 OG001-0.70± 0.28

Alertness - Reaction time tonic alertness

Title	Measurements
	OG000-0.90± 0.73 OG001-0.99± 0.73

Alertness - Reaction time phasic alertness

Title	Measurements
	OG000-1.03± 0.67 OG001-1.10± 0.66

Semantic fluency

Title	Measurements
	OG0000.02± 1.24 OG0010.09± 1.18

Phonemic fluency

Title	Measurements
	OG0000.32± 1.48 OG0010.21± 1.31

Digit Span backwards-Working memory

Title	Measurements
	OG0000.05± 0.86 OG001-0.01± 1.02

Trail Making Test - Time condition A

Title	Measurements
	OG000-0.32± 1.14 OG001-0.26± 1.06

Trail Making Test - Time condition B

Title	Measurements
	OG0000.16± 1.46 OG0010.18± 1.31

Trail Making Test - Condition B/A

Title	Measurements
	OG0000.37± 1.42 OG0010.36± 1.48

Social Cognition

Title	Measurements
	OG000-0.67± 1.20 OG001-0.71± 1.15

Group IDs	Group Description	Statistical Method	P-Value	P-Value Comment	Tested Non-Inferiority	Non-Inferiority Type
OG000 OG001	Rivermead Behavioural Memory Test (RBMT) - Immediate memory	Wilcoxon (Mann-Whitney)	0.861	A Bonferroni correction for multiple comparisons was applied, resulting in a significance level of 0.001.	No	Superiority or Other
OG000 OG001	RBMT - Delayed memory	Wilcoxon (Mann-Whitney)	0.668	A Bonferroni correction for multiple comparisons was applied, resulting in a significance level of 0.001.	No	Superiority or Other
OG000 OG001	RBMT-Delayed corrected for immediate memory	Wilcoxon (Mann-Whitney)	0.713	A Bonferroni correction for multiple comparisons was applied, resulting in a significance level of 0.001.	No	Superiority or Other
OG000 OG001	15 Words Test - Short-term memory	Wilcoxon (Mann-Whitney)	0.028	A Bonferroni correction for multiple comparisons was applied, resulting in a significance level of 0.001.	No	Superiority or Other
OG000 OG001	15 Words Test - Total immediate memory	Wilcoxon (Mann-Whitney)	0.227	A Bonferroni correction for multiple comparisons was applied, resulting in a significance level of 0.001.	No	Superiority or Other
OG000 OG001	15 Words Test - Learning Score	Wilcoxon (Mann-Whitney)	0.130	A Bonferroni correction for multiple comparisons was applied, resulting in a significance level of 0.001.	No	Superiority or Other
OG000 OG001	15 Words Test- Delayed memory	Wilcoxon (Mann-Whitney)	0.106	A Bonferroni correction for multiple comparisons was applied, resulting in a significance level of 0.001.	No	Superiority or Other
OG000 OG001	15 Words Test - Delayed corrected for total memory	Wilcoxon (Mann-Whitney)	0.350	A Bonferroni correction for multiple comparisons was applied, resulting in a significance level of 0.001.	No	Superiority or Other
OG000 OG001	15 Words Test - Recognition	Wilcoxon (Mann-Whitney)	0.093	A Bonferroni correction for multiple comparisons was applied, resulting in a significance level of 0.001.	No	Superiority or Other
OG000 OG001	Digit Span forward - Short-term memory	Wilcoxon (Mann-Whitney)	0.614	A Bonferroni correction for multiple comparisons was applied, resulting in a significance level of 0.001.	No	Superiority or Other
OG000 OG001	Rey Complex Figure - Immediate memory	Wilcoxon (Mann-Whitney)	0.111	A Bonferroni correction for multiple comparisons was applied, resulting in a significance level of 0.001.	No	Superiority or Other
OG000 OG001	Rey Complex Figure - Delayed memory	Wilcoxon (Mann-Whitney)	0.451	A Bonferroni correction for multiple comparisons was applied, resulting in a significance level of 0.001.	No	Superiority or Other
OG000 OG001	Divided attention-Reaction time auditory response	Wilcoxon (Mann-Whitney)	0.905	A Bonferroni correction for multiple comparisons was applied, resulting in a significance level of 0.001.	No	Superiority or Other
OG000 OG001	Divided attention-Reaction time visual response	Wilcoxon (Mann-Whitney)	0.502	A Bonferroni correction for multiple comparisons was applied, resulting in a significance level of 0.001.	No	Superiority or Other
OG000 OG001	Divided attention-Number of omission errors	Wilcoxon (Mann-Whitney)	0.531	A Bonferroni correction for multiple comparisons was applied, resulting in a significance level of 0.001.	No	Superiority or Other
OG000 OG001	Divided attention-Number of commission errors	Wilcoxon (Mann-Whitney)	0.681	A Bonferroni correction for multiple comparisons was applied, resulting in a significance level of 0.001.	No	Superiority or Other
OG000 OG001	Visual scanning - Reaction time for target stimuli	Wilcoxon (Mann-Whitney)	0.713	A Bonferroni correction for multiple comparisons was applied, resulting in a significance level of 0.001.	No	Superiority or Other
OG000 OG001	Visual scanning - Number of omission errors	Wilcoxon (Mann-Whitney)	0.229	A Bonferroni correction for multiple comparisons was applied, resulting in a significance level of 0.001.	No	Superiority or Other
OG000 OG001	Visual scanning - Number of commission errors	Wilcoxon (Mann-Whitney)	0.329	A Bonferroni correction for multiple comparisons was applied, resulting in a significance level of 0.001.	No	Superiority or Other
OG000 OG001	Alertness - Reaction time tonic alertness	Wilcoxon (Mann-Whitney)	0.192	A Bonferroni correction for multiple comparisons was applied, resulting in a significance level of 0.001.	No	Superiority or Other
OG000 OG001	Alertness - Reaction time phasic alertness	Wilcoxon (Mann-Whitney)	0.164	A Bonferroni correction for multiple comparisons was applied, resulting in a significance level of 0.001.	No	Superiority or Other
OG000 OG001	Semantic fluency	Wilcoxon (Mann-Whitney)	0.536	A Bonferroni correction for multiple comparisons was applied, resulting in a significance level of 0.001.	No	Superiority or Other
OG000 OG001	Phonemic fluency	Wilcoxon (Mann-Whitney)	0.572	A Bonferroni correction for multiple comparisons was applied, resulting in a significance level of 0.001.	No	Superiority or Other
OG000 OG001	Digit span backward - Working memory	Wilcoxon (Mann-Whitney)	0.632	A Bonferroni correction for multiple comparisons was applied, resulting in a significance level of 0.001.	No	Superiority or Other
OG000 OG001	Trail Making Test - Time condition A	Wilcoxon (Mann-Whitney)	0.512	A Bonferroni correction for multiple comparisons was applied, resulting in a significance level of 0.001.	No	Superiority or Other
OG000 OG001	Trail Making Test - Time condition B	Wilcoxon (Mann-Whitney)	0.861	A Bonferroni correction for multiple comparisons was applied, resulting in a significance level of 0.001.	No	Superiority or Other
OG000 OG001	Trail Making Test - Condition B/A	Wilcoxon (Mann-Whitney)	0.958	A Bonferroni correction for multiple comparisons was applied, resulting in a significance level of 0.001.	No	Superiority or Other
OG000 OG001	Social cognition	Wilcoxon (Mann-Whitney)	0.819	A Bonferroni correction for multiple comparisons was applied, resulting in a significance level of 0.001.	No	Superiority or Other